<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04456686</url>
  </required_header>
  <id_info>
    <org_study_id>17513</org_study_id>
    <secondary_id>H0P-MC-OA01</secondary_id>
    <nct_id>NCT04456686</nct_id>
  </id_info>
  <brief_title>Chronic Pain Master Protocol (CPMP): A Study of LY3016859 in Participants With Osteoarthritis</brief_title>
  <official_title>Randomized, Placebo-Controlled, Phase 2 Clinical Trial to Evaluate LY3016859 for the Treatment of Osteoarthritis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Eli Lilly and Company</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Eli Lilly and Company</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study is being done to test the safety and efficacy of LY3016859 for the treatment of&#xD;
      osteoarthritis pain. This trial is part of the chronic pain master protocol (H0P-MC-CPMP)&#xD;
      which is a protocol to accelerate the development of new treatments for chronic pain.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 1, 2020</start_date>
  <completion_date type="Actual">August 26, 2021</completion_date>
  <primary_completion_date type="Actual">April 22, 2021</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change From Baseline in Average Pain Intensity as Measured by the Numeric Rating Scale (NRS)</measure>
    <time_frame>Baseline, up to Week 8</time_frame>
    <description>The NRS was used during the preliminary data entry period and daily throughout the study to describe pain severity. Participants were asked to describe their average pain over the past 24 hours, on a scale of 0 to 10: 0 = no pain, and 10 = pain as bad as you can imagine.&#xD;
Posterior mean change from baseline, 95% credible interval (CrI) was derived using Bayesian mixed model repeated measures. The Bayesian analyses include posterior probabilities instead of p-values, and 95% credible intervals instead of 95% confidence intervals.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline on the Western Ontario and McMaster University (WOMAC®) Arthritis Index (WOMAC®) Pain Subscale</measure>
    <time_frame>Baseline, up to Week 8</time_frame>
    <description>The WOMAC® is a validated instrument that is extensively used to evaluate the response to medications for the treatment of Osteoarthritis pain. There are 5 questions on the pain subscale, and participants used a 0 to 4 Likert scale to answer each question for the current day: 0 = no pain, and 4 = extreme pain. The scores for the pain subscale were calculated by summing the scores of the questions for each participant at each time point. The range of possible scores is 0 to 20 for the pain subscale.&#xD;
Posterior mean change from baseline, 95% CrI was derived using Bayesian mixed model repeated measures. The Bayesian analyses include posterior probabilities instead of p-values, and 95% credible intervals instead of 95% confidence intervals.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline on the WOMAC® Stiffness Subscale</measure>
    <time_frame>Baseline, up to Week 8</time_frame>
    <description>The WOMAC® is a validated instrument that is extensively used to evaluate the response to medications for the treatment of Osteoarthritis pain. There are 2 questions in the stiffness subscale and participants used a 0 to 4 Likert scale to answer each question for the current day: 0 = no stiffness, and 4 = extreme stiffness. The scores for each subscale were calculated by summing the scores of the questions in each respective subscale for each participant at each time point. The range of possible scores is 0 to 8 for the stiffness subscale.&#xD;
Posterior mean change from baseline, 95% CrI was derived using Bayesian mixed model repeated measures. The Bayesian analyses include posterior probabilities instead of p-values, and 95% credible intervals instead of 95% confidence intervals.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline on the WOMAC® Physical Function Subscale</measure>
    <time_frame>Baseline, up to Week 8</time_frame>
    <description>The WOMAC® is a validated instrument that is extensively used to evaluate the response to medications for the treatment of Osteoarthritis pain. There are 17 questions in the physical function subscale, and participants used a 0 to 4 Likert scale to answer each question for the current day: 0 = no difficulty, and 4 = extreme difficulty. The scores for each subscale were calculated by summing the scores of the questions in each respective subscale for each participant at each time point. The range of possible scores is 0 to 68 for the physical function subscale.&#xD;
Posterior mean change from baseline, 95% CrI was derived using Bayesian mixed model repeated measures. The Bayesian analyses include posterior probabilities instead of p-values, and 95% credible intervals instead of 95% confidence intervals.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline for Overall Improvement as Measured by Patient's Global Impression of Change (PGI)</measure>
    <time_frame>Baseline, up to Week 8</time_frame>
    <description>Patients Global Impression of Change captured the participant's perspective of treatment apart from sub-aspects of the general improvement. This is a numeric scale from 1 to 7: 1 = very much better, and 7 = very much worse.&#xD;
Posterior mean change from baseline, 95% CrI was derived using Bayesian mixed model repeated measures. The Bayesian analyses include posterior probabilities instead of p-values, and 95% credible intervals instead of 95% confidence intervals.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline for Worst Pain Intensity as Measured by NRS</measure>
    <time_frame>Baseline, up to Week 8</time_frame>
    <description>The NRS was used during the preliminary data entry period and daily throughout the study to describe pain severity. Participants were asked to describe their worst pain over the past 24 hours, on a scale of 0 to 10: 0 = no pain, and 10 = pain as bad as you can imagine.&#xD;
Posterior mean change from baseline, 95% CrI was derived using Bayesian mixed model repeated measures. The Bayesian analyses include posterior probabilities instead of p-values, and 95% credible intervals instead of 95% confidence intervals.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline on the Visual Analog Scale (VAS) for Pain</measure>
    <time_frame>Baseline, up to Week 8</time_frame>
    <description>VAS was a graphic, single-item scale where participants were asked to describe their pain intensity over the past week, on a scale of 0 to 100: 0 = no pain, and 100 = worst imaginable pain. Participants completed the VAS by placing a line perpendicular to the VAS line at a point that described their pain intensity.&#xD;
Posterior mean change from baseline, 95% CrI was derived using Bayesian mixed model repeated measures. The Bayesian analyses include posterior probabilities instead of p-values, and 95% credible intervals instead of 95% confidence intervals.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline Assessment to Endpoint on the Sleep Scale From the Medical Outcomes Study (MOS Sleep Scale)</measure>
    <time_frame>Baseline, up to Week 8</time_frame>
    <description>The MOS Sleep Scale consists of 12 questions addressing the past week. Participants reported how often each sleep symptom or problem was present on a 5-point categorical scale ranging from 'all of the time' to 'none of the time.' It includes 12 questions with the first question assessing how long it takes the subject to fall asleep. The second question asks how many hours each night the subject slept. The remaining 10 questions have a range of 6 responses from 1=&quot;all of the time&quot; to 6=&quot;none of the time&quot;. MOS Sleep scale scores range from 0 (min) to 100 (max). The original survey items are converted to a 0 to 100 range (by Converting 1 to 0, 2 to 25, 3 to 50, 4 to 75, and 5 to 100). Higher scores represent worse outcomes.&#xD;
Posterior mean change from baseline, 95% CrI was derived using Bayesian longitudinal model. The Bayesian analyses include posterior probabilities instead of p-values, and 95% credible intervals instead of 95% confidence intervals.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total Amount of Rescue Medication Use as Measured by Average Dosage Per Week</measure>
    <time_frame>Baseline up to Week 8</time_frame>
    <description>Total Amount of Rescue Medication Use as Measured by Average Dosage per Week. Posterior mean change from baseline, 95% CrI was derived using Bayesian mixed model repeated measures. The Bayesian analyses include posterior probabilities instead of p-values, and 95% credible intervals instead of 95% confidence intervals.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline on the EuroQol-5D 5 Level Questionnaire (EQ-5D-5L) (United States)</measure>
    <time_frame>Baseline, up to Week 8</time_frame>
    <description>The EQ-5D-5L assessed quality of life based on 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. The participant was asked to 'check the ONE box that best describes your health TODAY,' choosing from 5 options (no problems, slight problems, moderate problems, severe problems, extreme problems) provided under each dimension. The scores in the 5 dimensions were summarized into a health state index score. The health state index value is a single value on a scale from less than 0 to 1 (negative values are valued as worse than dead) with higher scores indicating better health: 0 = a health state equivalent to death, and 1 = perfect health.&#xD;
Posterior mean change from baseline, 95% CrI was derived using Bayesian mixed model repeated measures. The Bayesian analyses include posterior probabilities instead of p-values, and 95% credible intervals instead of 95% confidence intervals.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">117</enrollment>
  <condition>Osteoarthritis</condition>
  <arm_group>
    <arm_group_label>750 Mg-500 mg LY3016859</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants received LY3016859 every 2 weeks with 750 milligram (mg) as starting dose followed by 500 mg intravenous (IV) infusion for a total of 4 doses.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants received placebo every 2 weeks by IV infusion for a total of 4 doses.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>LY3016859</intervention_name>
    <description>LY3016859 given IV.</description>
    <arm_group_label>750 Mg-500 mg LY3016859</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo given IV.</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Have a visual analog scale (VAS) pain value ≥40 and &lt;95 during screening.&#xD;
&#xD;
          -  Have a history of daily pain for at least 12 weeks based on participant report or&#xD;
             medical history.&#xD;
&#xD;
          -  Have a value of ≤30 on the pain catastrophizing scale.&#xD;
&#xD;
          -  Have a body mass index &lt;40 kilograms per meter squared (kg/m²) (inclusive).&#xD;
&#xD;
          -  Are willing to maintain a consistent regimen of any ongoing nonpharmacologic&#xD;
             pain-relieving therapies (for example, physical therapy) and will not start any new&#xD;
             nonpharmacologic pain-relieving therapies during study participation.&#xD;
&#xD;
          -  Are willing to discontinue all medications taken for chronic pain conditions for the&#xD;
             duration of the study.&#xD;
&#xD;
          -  Have presence of index knee pain for &gt;12 weeks at screening.&#xD;
&#xD;
          -  Have an x-ray supporting diagnosis of osteoarthritis according to the American College&#xD;
             of Rheumatology with a Kellgren-Lawrence grade 2 to 4 radiographic classification of&#xD;
             index knee.&#xD;
&#xD;
          -  Are men, or women able to abide by reproductive and contraceptive requirements.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Have second- or third-degree atrioventricular (AV) heart block or AV dissociation or&#xD;
             history of ventricular tachycardia.&#xD;
&#xD;
          -  Have had a procedure within the past 6 months intended to produce permanent sensory&#xD;
             loss in the target area of interest (for example, ablation techniques).&#xD;
&#xD;
          -  Have surgery planned during the study for any reason, related or not to the disease&#xD;
             state under evaluation.&#xD;
&#xD;
          -  Have, in the judgment of the investigator, an acute, serious, or unstable medical&#xD;
             condition or a history or presence of any other medical illness that would preclude&#xD;
             study participation.&#xD;
&#xD;
          -  There is an inability to rule out other causative or confounding sources of pain in&#xD;
             the primary condition under study.&#xD;
&#xD;
          -  Have had cancer within 2 years of baseline, except for cutaneous basal cell or&#xD;
             squamous cell carcinoma resolved by excision.&#xD;
&#xD;
          -  Have a substance use disorder as defined by the Diagnostic and Statistical Manual of&#xD;
             Mental Disorders (5th edition; DSM-5; American Psychiatric Association).&#xD;
&#xD;
          -  Have congenital QT prolongation or QT interval corrected for heart rate using&#xD;
             Fridericia's formula (QTcF) interval measurement &gt;450 milliseconds (msec) for male&#xD;
             participants, &gt;470 msec for female participants, or &gt;480 msec for participants with&#xD;
             bundle branch block.&#xD;
&#xD;
          -  Have any clinically important abnormality at screening, as determined by investigator,&#xD;
             in physical or neurological examination, vital signs, electrocardiogram (ECG), or&#xD;
             clinical laboratory test results that could be detrimental to the participant or could&#xD;
             compromise the study.&#xD;
&#xD;
          -  Have a positive human immunodeficiency virus (HIV) test result at screening.&#xD;
&#xD;
          -  Are, in the judgment of the investigator, actively suicidal and therefore deemed to be&#xD;
             at significant risk for suicide.&#xD;
&#xD;
          -  Have an intolerance to acetaminophen or paracetamol or any of its excipients.&#xD;
&#xD;
          -  Have a history of alcohol, illicit drug, analgesic or narcotic use disorder within 2&#xD;
             years prior to screening.&#xD;
&#xD;
          -  Are largely or wholly incapacitated and unable to participate fully in all protocol&#xD;
             procedures, for example, bedridden or confined to a wheelchair, permitting little or&#xD;
             no selfcare.&#xD;
&#xD;
          -  Have presence of surgical hardware or other foreign body in the index knee.&#xD;
&#xD;
          -  Have an unstable index joint (such as a torn anterior cruciate ligament).&#xD;
&#xD;
          -  Have had a surgical procedure or therapeutic injection in the affected knee within 3&#xD;
             months prior to starting the washout period.&#xD;
&#xD;
          -  Have fibromyalgia, chronic pain syndrome, or other concurrent medical or arthritic&#xD;
             conditions that could interfere with the evaluation of the index knee.&#xD;
&#xD;
          -  Have a history of Reiter's syndrome, rheumatoid arthritis, psoriatic arthritis,&#xD;
             ankylosing spondylitis, arthritis associated with inflammatory bowel disease,&#xD;
             sarcoidosis, or amyloidosis.&#xD;
&#xD;
          -  Have clinical signs and symptoms of active knee infection or crystal disease of the&#xD;
             index knee.&#xD;
&#xD;
          -  Have a history of infection in the index joint.&#xD;
&#xD;
          -  Have a history of arthritis due to crystals (e.g., gout, pseudogout).&#xD;
&#xD;
          -  Have pain or functional impairment due to ipsilateral hip osteoarthritis.&#xD;
&#xD;
          -  Have had an intra-articular injection of hyaluronic acid within 24 weeks of screening.&#xD;
&#xD;
          -  Have an estimated glomerular filtration rate (eGFR) of less than 70&#xD;
             milliliters/minute/1.73m² during screening.&#xD;
&#xD;
          -  Have any clinically serious or unstable cardiovascular, musculoskeletal disorder,&#xD;
             gastrointestinal, endocrinologic, hematologic, hepatic, metabolic, urologic,&#xD;
             pulmonary, dermatologic, immunologic, or ophthalmologic disease within 3 months of&#xD;
             baseline.&#xD;
&#xD;
          -  Have received any antibodies against nerve growth factor (NGF), or antibodies against&#xD;
             EGFR, or EGFR tyrosine kinase inhibitors.&#xD;
&#xD;
          -  Have a history of allergic reactions to monoclonal antibodies, or clinically&#xD;
             significant multiple or severe drug allergies, including but not limited to erythema&#xD;
             multiforme major, linear immunoglobulin A dermatosis, toxic epidermal necrolysis, or&#xD;
             exfoliative dermatitis.&#xD;
&#xD;
          -  Have a history or presence of uncontrolled asthma, eczema, significant atopy,&#xD;
             significant hereditary angioedema or common variable immune deficiency.&#xD;
&#xD;
          -  Have hade any joint replacement such as joint knee of the lower extremity such as hip,&#xD;
             knee, or ankle in the past 6 months.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM -5 PM Eastern time (UTC/GMT - 5 hours, EST)</last_name>
    <role>Study Director</role>
    <affiliation>Eli Lilly and Company</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Simon Williamson Clinic</name>
      <address>
        <city>Birmingham</city>
        <state>Alabama</state>
        <zip>35211</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Synexus- Chandler</name>
      <address>
        <city>Chandler</city>
        <state>Arizona</state>
        <zip>85224</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Synexus Clinical Research - Glendale</name>
      <address>
        <city>Glendale</city>
        <state>Arizona</state>
        <zip>85306</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Irvine Clinical Research Center</name>
      <address>
        <city>Irvine</city>
        <state>California</state>
        <zip>92614</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Artemis Institute for Clinical Research</name>
      <address>
        <city>Riverside</city>
        <state>California</state>
        <zip>92503</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Artemis Institute for Clinical Research</name>
      <address>
        <city>San Diego</city>
        <state>California</state>
        <zip>92103</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Suncoast Research Group</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33135</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Renstar Medical Research</name>
      <address>
        <city>Ocala</city>
        <state>Florida</state>
        <zip>34470</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Synexus - US</name>
      <address>
        <city>Orlando</city>
        <state>Florida</state>
        <zip>32806</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Synexus - US</name>
      <address>
        <city>Pinellas Park</city>
        <state>Florida</state>
        <zip>33781</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Gold Coast Research</name>
      <address>
        <city>Plantation</city>
        <state>Florida</state>
        <zip>33317</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Synexus Clinical Research US, Inc - Orlando</name>
      <address>
        <city>The Villages</city>
        <state>Florida</state>
        <zip>32162</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Synexus Clinical Research</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60602</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Northwestern University</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60611</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cotton O'Neil Infusion Center</name>
      <address>
        <city>Topeka</city>
        <state>Kansas</state>
        <zip>66606</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ActivMed Practices and Research</name>
      <address>
        <city>Methuen</city>
        <state>Massachusetts</state>
        <zip>01844</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MedVadis Research Corporation</name>
      <address>
        <city>Waltham</city>
        <state>Massachusetts</state>
        <zip>02451</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Great Lakes Research Group, Inc.</name>
      <address>
        <city>Bay City</city>
        <state>Michigan</state>
        <zip>48706</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>StudyMetrix Research</name>
      <address>
        <city>Saint Peters</city>
        <state>Missouri</state>
        <zip>63303</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Synexus - US</name>
      <address>
        <city>Omaha</city>
        <state>Nebraska</state>
        <zip>68144</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>PharmQuest</name>
      <address>
        <city>Greensboro</city>
        <state>North Carolina</state>
        <zip>27408</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Synexus - Cincinnati</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45236</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rapid Medical Research</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44122</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Aventiv Research Inc</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43213</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Altoona Center For Clinical Research</name>
      <address>
        <city>Duncansville</city>
        <state>Pennsylvania</state>
        <zip>16635</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Research Center of Reading,LLC</name>
      <address>
        <city>Wyomissing</city>
        <state>Pennsylvania</state>
        <zip>19610</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Coastal Carolina Research Center</name>
      <address>
        <city>North Charleston</city>
        <state>South Carolina</state>
        <zip>29405</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Synexus - US</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75234</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Synexus - US</name>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <zip>78229</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Synexus - US</name>
      <address>
        <city>Murray</city>
        <state>Utah</state>
        <zip>84123</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Northwest Clinical Research Center</name>
      <address>
        <city>Bellevue</city>
        <state>Washington</state>
        <zip>98007-4209</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rainier Clinical Research Center</name>
      <address>
        <city>Renton</city>
        <state>Washington</state>
        <zip>98057</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Latin Clinical Trial Center</name>
      <address>
        <city>San Juan</city>
        <zip>00909</zip>
        <country>Puerto Rico</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Puerto Rico</country>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://trials.lillytrialguide.com/en-US/trial/6VXLrQld1Oc5hSVgHZh3OP</url>
    <description>Chronic Pain Master Protocol (CPMP): A Study of LY3016859 in Participants with Osteoarthritis</description>
  </link>
  <verification_date>August 2022</verification_date>
  <study_first_submitted>July 1, 2020</study_first_submitted>
  <study_first_submitted_qc>July 1, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 2, 2020</study_first_posted>
  <results_first_submitted>April 15, 2022</results_first_submitted>
  <results_first_submitted_qc>May 31, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">June 23, 2022</results_first_posted>
  <last_update_submitted>August 19, 2022</last_update_submitted>
  <last_update_submitted_qc>August 19, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">September 14, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Osteoarthritis</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_time_frame>Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.</ipd_time_frame>
    <ipd_access_criteria>A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.</ipd_access_criteria>
    <ipd_url>https://vivli.org/</ipd_url>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>March 27, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/86/NCT04456686/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>October 19, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/86/NCT04456686/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>750 Mg-500 Milligram (mg) LY3016859</title>
          <description>Participants received LY3016859 every 2 weeks with 750 mg as starting dose followed by 500 mg IV infusion for a total of 4 doses.</description>
        </group>
        <group group_id="P2">
          <title>Placebo</title>
          <description>Participants received placebo every 2 weeks by IV infusion for a total of 4 doses.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="78"/>
                <participants group_id="P2" count="39"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Received at Least 1 Dose of Study Drug</title>
              <participants_list>
                <participants group_id="P1" count="77"/>
                <participants group_id="P2" count="36"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="63"/>
                <participants group_id="P2" count="32"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="15"/>
                <participants group_id="P2" count="7"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lack of Efficacy</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrew consent</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Protocol Violation</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>All enrolled or randomized participants who received at least one dose of study drug.</population>
      <group_list>
        <group group_id="B1">
          <title>750 Mg-500 mg LY3016859</title>
          <description>Participants received LY3016859 every 2 weeks with 750 mg as starting dose followed by 500 mg IV infusion for a total of 4 doses.</description>
        </group>
        <group group_id="B2">
          <title>Placebo</title>
          <description>Participants received placebo every 2 weeks by IV infusion for a total of 4 doses.</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="78"/>
            <count group_id="B2" value="39"/>
            <count group_id="B3" value="117"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="39"/>
                    <measurement group_id="B2" value="23"/>
                    <measurement group_id="B3" value="62"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="39"/>
                    <measurement group_id="B2" value="16"/>
                    <measurement group_id="B3" value="55"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="63.3" spread="9.2"/>
                    <measurement group_id="B2" value="61.7" spread="8.9"/>
                    <measurement group_id="B3" value="62.8" spread="9.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="48"/>
                    <measurement group_id="B2" value="29"/>
                    <measurement group_id="B3" value="77"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="30"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="40"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="13"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="67"/>
                    <measurement group_id="B2" value="37"/>
                    <measurement group_id="B3" value="104"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="11"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="68"/>
                    <measurement group_id="B2" value="33"/>
                    <measurement group_id="B3" value="101"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="78"/>
                    <measurement group_id="B2" value="39"/>
                    <measurement group_id="B3" value="117"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Average Pain Intensity as Measured by the Numeric Rating Scale (NRS)</title>
          <description>The NRS was used during the preliminary data entry period and daily throughout the study to describe pain severity. Participants were asked to describe their average pain over the past 24 hours, on a scale of 0 to 10: 0 = no pain, and 10 = pain as bad as you can imagine.</description>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5.67" spread="1.51"/>
                    <measurement group_id="B2" value="5.47" spread="1.56"/>
                    <measurement group_id="B3" value="5.61" spread="1.52"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline in Average Pain Intensity as Measured by the Numeric Rating Scale (NRS)</title>
        <description>The NRS was used during the preliminary data entry period and daily throughout the study to describe pain severity. Participants were asked to describe their average pain over the past 24 hours, on a scale of 0 to 10: 0 = no pain, and 10 = pain as bad as you can imagine.&#xD;
Posterior mean change from baseline, 95% credible interval (CrI) was derived using Bayesian mixed model repeated measures. The Bayesian analyses include posterior probabilities instead of p-values, and 95% credible intervals instead of 95% confidence intervals.</description>
        <time_frame>Baseline, up to Week 8</time_frame>
        <population>All enrolled or randomized participants who received at least one dose of study drug. Here, the overall number of participants analyzed includes the number of participants with non-missing value at Week 8.</population>
        <group_list>
          <group group_id="O1">
            <title>750 Mg-500 mg LY3016859</title>
            <description>Participants received LY3016859 every 2 weeks with 750 mg as starting dose followed by 500 mg IV infusion for a total of 4 doses.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants received placebo every 2 weeks by IV infusion for a total of 4 doses.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Average Pain Intensity as Measured by the Numeric Rating Scale (NRS)</title>
          <description>The NRS was used during the preliminary data entry period and daily throughout the study to describe pain severity. Participants were asked to describe their average pain over the past 24 hours, on a scale of 0 to 10: 0 = no pain, and 10 = pain as bad as you can imagine.&#xD;
Posterior mean change from baseline, 95% credible interval (CrI) was derived using Bayesian mixed model repeated measures. The Bayesian analyses include posterior probabilities instead of p-values, and 95% credible intervals instead of 95% confidence intervals.</description>
          <population>All enrolled or randomized participants who received at least one dose of study drug. Here, the overall number of participants analyzed includes the number of participants with non-missing value at Week 8.</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="63"/>
                <count group_id="O2" value="31"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.04" lower_limit="-2.46" upper_limit="-1.61"/>
                    <measurement group_id="O2" value="-2.00" lower_limit="-2.61" upper_limit="-1.39"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <param_type>Posterior Mean Difference</param_type>
            <param_value>-0.03</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.77</ci_lower_limit>
            <ci_upper_limit>0.70</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline on the Western Ontario and McMaster University (WOMAC®) Arthritis Index (WOMAC®) Pain Subscale</title>
        <description>The WOMAC® is a validated instrument that is extensively used to evaluate the response to medications for the treatment of Osteoarthritis pain. There are 5 questions on the pain subscale, and participants used a 0 to 4 Likert scale to answer each question for the current day: 0 = no pain, and 4 = extreme pain. The scores for the pain subscale were calculated by summing the scores of the questions for each participant at each time point. The range of possible scores is 0 to 20 for the pain subscale.&#xD;
Posterior mean change from baseline, 95% CrI was derived using Bayesian mixed model repeated measures. The Bayesian analyses include posterior probabilities instead of p-values, and 95% credible intervals instead of 95% confidence intervals.</description>
        <time_frame>Baseline, up to Week 8</time_frame>
        <population>All enrolled or randomized participants who received at least one dose of study drug. Here, the overall number of participants analyzed includes the number of participants with non-missing value at Week 8.</population>
        <group_list>
          <group group_id="O1">
            <title>750 Mg-500 mg LY3016859</title>
            <description>Participants received LY3016859 every 2 weeks with 750 mg as starting dose followed by 500 mg IV infusion for a total of 4 doses.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants received placebo every 2 weeks by IV infusion for a total of 4 doses.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline on the Western Ontario and McMaster University (WOMAC®) Arthritis Index (WOMAC®) Pain Subscale</title>
          <description>The WOMAC® is a validated instrument that is extensively used to evaluate the response to medications for the treatment of Osteoarthritis pain. There are 5 questions on the pain subscale, and participants used a 0 to 4 Likert scale to answer each question for the current day: 0 = no pain, and 4 = extreme pain. The scores for the pain subscale were calculated by summing the scores of the questions for each participant at each time point. The range of possible scores is 0 to 20 for the pain subscale.&#xD;
Posterior mean change from baseline, 95% CrI was derived using Bayesian mixed model repeated measures. The Bayesian analyses include posterior probabilities instead of p-values, and 95% credible intervals instead of 95% confidence intervals.</description>
          <population>All enrolled or randomized participants who received at least one dose of study drug. Here, the overall number of participants analyzed includes the number of participants with non-missing value at Week 8.</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="63"/>
                <count group_id="O2" value="31"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-3.64" lower_limit="-4.46" upper_limit="-2.83"/>
                    <measurement group_id="O2" value="-4.22" lower_limit="-5.35" upper_limit="-3.06"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <param_type>Posterior Mean Difference</param_type>
            <param_value>0.58</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.82</ci_lower_limit>
            <ci_upper_limit>1.96</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline on the WOMAC® Stiffness Subscale</title>
        <description>The WOMAC® is a validated instrument that is extensively used to evaluate the response to medications for the treatment of Osteoarthritis pain. There are 2 questions in the stiffness subscale and participants used a 0 to 4 Likert scale to answer each question for the current day: 0 = no stiffness, and 4 = extreme stiffness. The scores for each subscale were calculated by summing the scores of the questions in each respective subscale for each participant at each time point. The range of possible scores is 0 to 8 for the stiffness subscale.&#xD;
Posterior mean change from baseline, 95% CrI was derived using Bayesian mixed model repeated measures. The Bayesian analyses include posterior probabilities instead of p-values, and 95% credible intervals instead of 95% confidence intervals.</description>
        <time_frame>Baseline, up to Week 8</time_frame>
        <population>All enrolled or randomized participants who received at least one dose of study drug. Here, the overall number of participants analyzed includes the number of participants with non-missing value at Week 8.</population>
        <group_list>
          <group group_id="O1">
            <title>750 Mg-500 mg LY3016859</title>
            <description>Participants received LY3016859 every 2 weeks with 750 mg as starting dose followed by 500 mg IV infusion for a total of 4 doses.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants received placebo every 2 weeks by IV infusion for a total of 4 doses.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline on the WOMAC® Stiffness Subscale</title>
          <description>The WOMAC® is a validated instrument that is extensively used to evaluate the response to medications for the treatment of Osteoarthritis pain. There are 2 questions in the stiffness subscale and participants used a 0 to 4 Likert scale to answer each question for the current day: 0 = no stiffness, and 4 = extreme stiffness. The scores for each subscale were calculated by summing the scores of the questions in each respective subscale for each participant at each time point. The range of possible scores is 0 to 8 for the stiffness subscale.&#xD;
Posterior mean change from baseline, 95% CrI was derived using Bayesian mixed model repeated measures. The Bayesian analyses include posterior probabilities instead of p-values, and 95% credible intervals instead of 95% confidence intervals.</description>
          <population>All enrolled or randomized participants who received at least one dose of study drug. Here, the overall number of participants analyzed includes the number of participants with non-missing value at Week 8.</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="63"/>
                <count group_id="O2" value="31"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.44" lower_limit="-1.81" upper_limit="-1.08"/>
                    <measurement group_id="O2" value="-1.54" lower_limit="-2.02" upper_limit="-1.06"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <param_type>Posterior Mean Difference</param_type>
            <param_value>0.10</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.45</ci_lower_limit>
            <ci_upper_limit>0.63</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline on the WOMAC® Physical Function Subscale</title>
        <description>The WOMAC® is a validated instrument that is extensively used to evaluate the response to medications for the treatment of Osteoarthritis pain. There are 17 questions in the physical function subscale, and participants used a 0 to 4 Likert scale to answer each question for the current day: 0 = no difficulty, and 4 = extreme difficulty. The scores for each subscale were calculated by summing the scores of the questions in each respective subscale for each participant at each time point. The range of possible scores is 0 to 68 for the physical function subscale.&#xD;
Posterior mean change from baseline, 95% CrI was derived using Bayesian mixed model repeated measures. The Bayesian analyses include posterior probabilities instead of p-values, and 95% credible intervals instead of 95% confidence intervals.</description>
        <time_frame>Baseline, up to Week 8</time_frame>
        <population>All enrolled or randomized participants who received at least one dose of study drug. Here, the overall number of participants analyzed includes the number of participants with non-missing value at Week 8.</population>
        <group_list>
          <group group_id="O1">
            <title>750 Mg-500 mg LY3016859</title>
            <description>Participants received LY3016859 every 2 weeks with 750 mg as starting dose followed by 500 mg IV infusion for a total of 4 doses.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants received placebo every 2 weeks by IV infusion for a total of 4 doses.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline on the WOMAC® Physical Function Subscale</title>
          <description>The WOMAC® is a validated instrument that is extensively used to evaluate the response to medications for the treatment of Osteoarthritis pain. There are 17 questions in the physical function subscale, and participants used a 0 to 4 Likert scale to answer each question for the current day: 0 = no difficulty, and 4 = extreme difficulty. The scores for each subscale were calculated by summing the scores of the questions in each respective subscale for each participant at each time point. The range of possible scores is 0 to 68 for the physical function subscale.&#xD;
Posterior mean change from baseline, 95% CrI was derived using Bayesian mixed model repeated measures. The Bayesian analyses include posterior probabilities instead of p-values, and 95% credible intervals instead of 95% confidence intervals.</description>
          <population>All enrolled or randomized participants who received at least one dose of study drug. Here, the overall number of participants analyzed includes the number of participants with non-missing value at Week 8.</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="63"/>
                <count group_id="O2" value="31"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-11.59" lower_limit="-14.18" upper_limit="-9.01"/>
                    <measurement group_id="O2" value="-12.49" lower_limit="-16.07" upper_limit="-8.94"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <param_type>Posterior Mean Difference</param_type>
            <param_value>0.90</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-3.31</ci_lower_limit>
            <ci_upper_limit>5.06</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline for Overall Improvement as Measured by Patient's Global Impression of Change (PGI)</title>
        <description>Patients Global Impression of Change captured the participant's perspective of treatment apart from sub-aspects of the general improvement. This is a numeric scale from 1 to 7: 1 = very much better, and 7 = very much worse.&#xD;
Posterior mean change from baseline, 95% CrI was derived using Bayesian mixed model repeated measures. The Bayesian analyses include posterior probabilities instead of p-values, and 95% credible intervals instead of 95% confidence intervals.</description>
        <time_frame>Baseline, up to Week 8</time_frame>
        <population>All enrolled or randomized participants who received at least one dose of study drug. Here, the overall number of participants analyzed includes the number of participants with non-missing value at Week 8.</population>
        <group_list>
          <group group_id="O1">
            <title>750 Mg-500 mg LY3016859</title>
            <description>Participants received LY3016859 every 2 weeks with 750 mg as starting dose followed by 500 mg IV infusion for a total of 4 doses.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants received placebo every 2 weeks by IV infusion for a total of 4 doses.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline for Overall Improvement as Measured by Patient's Global Impression of Change (PGI)</title>
          <description>Patients Global Impression of Change captured the participant's perspective of treatment apart from sub-aspects of the general improvement. This is a numeric scale from 1 to 7: 1 = very much better, and 7 = very much worse.&#xD;
Posterior mean change from baseline, 95% CrI was derived using Bayesian mixed model repeated measures. The Bayesian analyses include posterior probabilities instead of p-values, and 95% credible intervals instead of 95% confidence intervals.</description>
          <population>All enrolled or randomized participants who received at least one dose of study drug. Here, the overall number of participants analyzed includes the number of participants with non-missing value at Week 8.</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="63"/>
                <count group_id="O2" value="31"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.74" lower_limit="2.47" upper_limit="3.02"/>
                    <measurement group_id="O2" value="2.71" lower_limit="2.33" upper_limit="3.11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <param_type>Posterior Mean Difference</param_type>
            <param_value>0.03</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.46</ci_lower_limit>
            <ci_upper_limit>0.50</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline for Worst Pain Intensity as Measured by NRS</title>
        <description>The NRS was used during the preliminary data entry period and daily throughout the study to describe pain severity. Participants were asked to describe their worst pain over the past 24 hours, on a scale of 0 to 10: 0 = no pain, and 10 = pain as bad as you can imagine.&#xD;
Posterior mean change from baseline, 95% CrI was derived using Bayesian mixed model repeated measures. The Bayesian analyses include posterior probabilities instead of p-values, and 95% credible intervals instead of 95% confidence intervals.</description>
        <time_frame>Baseline, up to Week 8</time_frame>
        <population>All enrolled or randomized participants who received at least one dose of study drug. Here, the overall number of participants analyzed includes the number of participants with non-missing value at Week 8.</population>
        <group_list>
          <group group_id="O1">
            <title>750 Mg-500 mg LY3016859</title>
            <description>Participants received LY3016859 every 2 weeks with 750 mg as starting dose followed by 500 mg IV infusion for a total of 4 doses.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants received placebo every 2 weeks by IV infusion for a total of 4 doses.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline for Worst Pain Intensity as Measured by NRS</title>
          <description>The NRS was used during the preliminary data entry period and daily throughout the study to describe pain severity. Participants were asked to describe their worst pain over the past 24 hours, on a scale of 0 to 10: 0 = no pain, and 10 = pain as bad as you can imagine.&#xD;
Posterior mean change from baseline, 95% CrI was derived using Bayesian mixed model repeated measures. The Bayesian analyses include posterior probabilities instead of p-values, and 95% credible intervals instead of 95% confidence intervals.</description>
          <population>All enrolled or randomized participants who received at least one dose of study drug. Here, the overall number of participants analyzed includes the number of participants with non-missing value at Week 8.</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="63"/>
                <count group_id="O2" value="31"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.15" lower_limit="-2.62" upper_limit="-1.68"/>
                    <measurement group_id="O2" value="-2.26" lower_limit="-2.92" upper_limit="-1.58"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <param_type>Posterior Mean Difference</param_type>
            <param_value>0.11</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.72</ci_lower_limit>
            <ci_upper_limit>0.91</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline on the Visual Analog Scale (VAS) for Pain</title>
        <description>VAS was a graphic, single-item scale where participants were asked to describe their pain intensity over the past week, on a scale of 0 to 100: 0 = no pain, and 100 = worst imaginable pain. Participants completed the VAS by placing a line perpendicular to the VAS line at a point that described their pain intensity.&#xD;
Posterior mean change from baseline, 95% CrI was derived using Bayesian mixed model repeated measures. The Bayesian analyses include posterior probabilities instead of p-values, and 95% credible intervals instead of 95% confidence intervals.</description>
        <time_frame>Baseline, up to Week 8</time_frame>
        <population>All enrolled or randomized participants who received at least one dose of study drug. Here, the overall number of participants analyzed includes the number of participants with non-missing value at Week 8.</population>
        <group_list>
          <group group_id="O1">
            <title>750 Mg-500 mg LY3016859</title>
            <description>Participants received LY3016859 every 2 weeks with 750 mg as starting dose followed by 500 mg IV infusion for a total of 4 doses.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants received placebo every 2 weeks by IV infusion for a total of 4 doses.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline on the Visual Analog Scale (VAS) for Pain</title>
          <description>VAS was a graphic, single-item scale where participants were asked to describe their pain intensity over the past week, on a scale of 0 to 100: 0 = no pain, and 100 = worst imaginable pain. Participants completed the VAS by placing a line perpendicular to the VAS line at a point that described their pain intensity.&#xD;
Posterior mean change from baseline, 95% CrI was derived using Bayesian mixed model repeated measures. The Bayesian analyses include posterior probabilities instead of p-values, and 95% credible intervals instead of 95% confidence intervals.</description>
          <population>All enrolled or randomized participants who received at least one dose of study drug. Here, the overall number of participants analyzed includes the number of participants with non-missing value at Week 8.</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="63"/>
                <count group_id="O2" value="31"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-22.24" lower_limit="-28.03" upper_limit="-16.48"/>
                    <measurement group_id="O2" value="-24.69" lower_limit="-32.86" upper_limit="-16.53"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <param_type>Posterior Mean Difference</param_type>
            <param_value>2.45</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-7.27</ci_lower_limit>
            <ci_upper_limit>12.20</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline Assessment to Endpoint on the Sleep Scale From the Medical Outcomes Study (MOS Sleep Scale)</title>
        <description>The MOS Sleep Scale consists of 12 questions addressing the past week. Participants reported how often each sleep symptom or problem was present on a 5-point categorical scale ranging from 'all of the time' to 'none of the time.' It includes 12 questions with the first question assessing how long it takes the subject to fall asleep. The second question asks how many hours each night the subject slept. The remaining 10 questions have a range of 6 responses from 1=&quot;all of the time&quot; to 6=&quot;none of the time&quot;. MOS Sleep scale scores range from 0 (min) to 100 (max). The original survey items are converted to a 0 to 100 range (by Converting 1 to 0, 2 to 25, 3 to 50, 4 to 75, and 5 to 100). Higher scores represent worse outcomes.&#xD;
Posterior mean change from baseline, 95% CrI was derived using Bayesian longitudinal model. The Bayesian analyses include posterior probabilities instead of p-values, and 95% credible intervals instead of 95% confidence intervals.</description>
        <time_frame>Baseline, up to Week 8</time_frame>
        <population>All enrolled or randomized participants who received at least one dose of study drug. Here, the overall number of participants analyzed includes the number of participants with non-missing value at Week 8.</population>
        <group_list>
          <group group_id="O1">
            <title>750 Mg-500 mg LY3016859</title>
            <description>Participants received LY3016859 every 2 weeks with 750 mg as starting dose followed by 500 mg IV infusion for a total of 4 doses.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants received placebo every 2 weeks by IV infusion for a total of 4 doses.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline Assessment to Endpoint on the Sleep Scale From the Medical Outcomes Study (MOS Sleep Scale)</title>
          <description>The MOS Sleep Scale consists of 12 questions addressing the past week. Participants reported how often each sleep symptom or problem was present on a 5-point categorical scale ranging from 'all of the time' to 'none of the time.' It includes 12 questions with the first question assessing how long it takes the subject to fall asleep. The second question asks how many hours each night the subject slept. The remaining 10 questions have a range of 6 responses from 1=&quot;all of the time&quot; to 6=&quot;none of the time&quot;. MOS Sleep scale scores range from 0 (min) to 100 (max). The original survey items are converted to a 0 to 100 range (by Converting 1 to 0, 2 to 25, 3 to 50, 4 to 75, and 5 to 100). Higher scores represent worse outcomes.&#xD;
Posterior mean change from baseline, 95% CrI was derived using Bayesian longitudinal model. The Bayesian analyses include posterior probabilities instead of p-values, and 95% credible intervals instead of 95% confidence intervals.</description>
          <population>All enrolled or randomized participants who received at least one dose of study drug. Here, the overall number of participants analyzed includes the number of participants with non-missing value at Week 8.</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="62"/>
                <count group_id="O2" value="31"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.30" lower_limit="0.01" upper_limit="0.58"/>
                    <measurement group_id="O2" value="-0.10" lower_limit="-0.49" upper_limit="0.28"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <param_type>Posterior Mean Difference</param_type>
            <param_value>0.40</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.04</ci_lower_limit>
            <ci_upper_limit>0.85</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Total Amount of Rescue Medication Use as Measured by Average Dosage Per Week</title>
        <description>Total Amount of Rescue Medication Use as Measured by Average Dosage per Week. Posterior mean change from baseline, 95% CrI was derived using Bayesian mixed model repeated measures. The Bayesian analyses include posterior probabilities instead of p-values, and 95% credible intervals instead of 95% confidence intervals.</description>
        <time_frame>Baseline up to Week 8</time_frame>
        <population>All enrolled or randomized participants who received at least one dose of study drug. Here, the overall number of participants analyzed includes the number of participants with non-missing value at Week 8.</population>
        <group_list>
          <group group_id="O1">
            <title>750 Mg-500 mg LY3016859</title>
            <description>Participants received LY3016859 every 2 weeks with 750 mg as starting dose followed by 500 mg IV infusion for a total of 4 doses.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants received placebo every 2 weeks by IV infusion for a total of 4 doses.</description>
          </group>
        </group_list>
        <measure>
          <title>Total Amount of Rescue Medication Use as Measured by Average Dosage Per Week</title>
          <description>Total Amount of Rescue Medication Use as Measured by Average Dosage per Week. Posterior mean change from baseline, 95% CrI was derived using Bayesian mixed model repeated measures. The Bayesian analyses include posterior probabilities instead of p-values, and 95% credible intervals instead of 95% confidence intervals.</description>
          <population>All enrolled or randomized participants who received at least one dose of study drug. Here, the overall number of participants analyzed includes the number of participants with non-missing value at Week 8.</population>
          <units>mg per week</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="63"/>
                <count group_id="O2" value="31"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="346.30" lower_limit="228.28" upper_limit="466.45"/>
                    <measurement group_id="O2" value="177.68" lower_limit="7.33" upper_limit="347.75"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <param_type>Posterior Mean Difference</param_type>
            <param_value>168.61</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-38.22</ci_lower_limit>
            <ci_upper_limit>379.20</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline on the EuroQol-5D 5 Level Questionnaire (EQ-5D-5L) (United States)</title>
        <description>The EQ-5D-5L assessed quality of life based on 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. The participant was asked to 'check the ONE box that best describes your health TODAY,' choosing from 5 options (no problems, slight problems, moderate problems, severe problems, extreme problems) provided under each dimension. The scores in the 5 dimensions were summarized into a health state index score. The health state index value is a single value on a scale from less than 0 to 1 (negative values are valued as worse than dead) with higher scores indicating better health: 0 = a health state equivalent to death, and 1 = perfect health.&#xD;
Posterior mean change from baseline, 95% CrI was derived using Bayesian mixed model repeated measures. The Bayesian analyses include posterior probabilities instead of p-values, and 95% credible intervals instead of 95% confidence intervals.</description>
        <time_frame>Baseline, up to Week 8</time_frame>
        <population>All enrolled or randomized participants who received at least one dose of study drug. Here, the overall number of participants analyzed includes the number of participants with non-missing value at Week 8.</population>
        <group_list>
          <group group_id="O1">
            <title>750 Mg-500 mg LY3016859</title>
            <description>Participants received LY3016859 every 2 weeks with 750 mg as starting dose followed by 500 mg IV infusion for a total of 4 doses.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants received placebo every 2 weeks by IV infusion for a total of 4 doses.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline on the EuroQol-5D 5 Level Questionnaire (EQ-5D-5L) (United States)</title>
          <description>The EQ-5D-5L assessed quality of life based on 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. The participant was asked to 'check the ONE box that best describes your health TODAY,' choosing from 5 options (no problems, slight problems, moderate problems, severe problems, extreme problems) provided under each dimension. The scores in the 5 dimensions were summarized into a health state index score. The health state index value is a single value on a scale from less than 0 to 1 (negative values are valued as worse than dead) with higher scores indicating better health: 0 = a health state equivalent to death, and 1 = perfect health.&#xD;
Posterior mean change from baseline, 95% CrI was derived using Bayesian mixed model repeated measures. The Bayesian analyses include posterior probabilities instead of p-values, and 95% credible intervals instead of 95% confidence intervals.</description>
          <population>All enrolled or randomized participants who received at least one dose of study drug. Here, the overall number of participants analyzed includes the number of participants with non-missing value at Week 8.</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="63"/>
                <count group_id="O2" value="31"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.04" lower_limit="0.00" upper_limit="0.08"/>
                    <measurement group_id="O2" value="0.05" lower_limit="0.00" upper_limit="0.11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <param_type>Posterior Mean Difference</param_type>
            <param_value>-0.01</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.07</ci_lower_limit>
            <ci_upper_limit>0.06</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Baseline through Week 26</time_frame>
      <desc>All enrolled or randomized participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.</desc>
      <group_list>
        <group group_id="E1">
          <title>750 Mg-500 mg LY3016859</title>
          <description>Participants received LY3016859 every 2 weeks with 750 mg as starting dose followed by 500 mg IV infusion for a total of 4 doses.</description>
        </group>
        <group group_id="E2">
          <title>Placebo</title>
          <description>Participants received placebo every 2 weeks by IV infusion for a total of 4 doses.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 24.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="77"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="77"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="36"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Supraventricular tachycardia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="77"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="36"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Nephrolithiasis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="77"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="36"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>3</frequency_threshold>
        <default_vocab>MedDRA 24.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="18" subjects_at_risk="77"/>
                <counts group_id="E2" subjects_affected="11" subjects_at_risk="36"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="77"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="36"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="77"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Peripheral swelling</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="77"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="36"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="77"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Vulvovaginal mycotic infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="47"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="26"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="77"/>
                <counts group_id="E2" events="8" subjects_affected="5" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="77"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="36"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="77"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="77"/>
                <counts group_id="E2" events="5" subjects_affected="3" subjects_at_risk="36"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Benign prostatic hyperplasia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Erectile dysfunction</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" events="5" subjects_affected="4" subjects_at_risk="77"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="36"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Chief Medical Officer</name_or_title>
      <organization>Eli Lilly and Company</organization>
      <phone>800-545-5979</phone>
      <email>ClinicalTrials.gov@lilly.com</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04456686
org study id: 17513
secondary id: H0P-MC-OA01
nct id: NCT04456686
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This study is being done to test the safety and efficacy of LY3016859 for the treatment of
      osteoarthritis pain. This trial is part of the chronic pain master protocol (H0P-MC-CPMP)
      which is a protocol to accelerate the development of new treatments for chronic pain.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Change From Baseline in Average Pain Intensity as Measured by the Numeric Rating Scale (NRS)
time frame: Baseline, up to Week 8
description: The NRS was used during the preliminary data entry period and daily throughout the study to describe pain severity. Participants were asked to describe their average pain over the past 24 hours, on a scale of 0 to 10: 0 = no pain, and 10 = pain as bad as you can imagine.
Posterior mean change from baseline, 95% credible interval (CrI) was derived using Bayesian mixed model repeated measures. The Bayesian analyses include posterior probabilities instead of p-values, and 95% credible intervals instead of 95% confidence intervals.
measure: Change From Baseline on the Western Ontario and McMaster University (WOMAC®) Arthritis Index (WOMAC®) Pain Subscale
time frame: Baseline, up to Week 8
description: The WOMAC® is a validated instrument that is extensively used to evaluate the response to medications for the treatment of Osteoarthritis pain. There are 5 questions on the pain subscale, and participants used a 0 to 4 Likert scale to answer each question for the current day: 0 = no pain, and 4 = extreme pain. The scores for the pain subscale were calculated by summing the scores of the questions for each participant at each time point. The range of possible scores is 0 to 20 for the pain subscale.
Posterior mean change from baseline, 95% CrI was derived using Bayesian mixed model repeated measures. The Bayesian analyses include posterior probabilities instead of p-values, and 95% credible intervals instead of 95% confidence intervals.
measure: Change From Baseline on the WOMAC® Stiffness Subscale
time frame: Baseline, up to Week 8
description: The WOMAC® is a validated instrument that is extensively used to evaluate the response to medications for the treatment of Osteoarthritis pain. There are 2 questions in the stiffness subscale and participants used a 0 to 4 Likert scale to answer each question for the current day: 0 = no stiffness, and 4 = extreme stiffness. The scores for each subscale were calculated by summing the scores of the questions in each respective subscale for each participant at each time point. The range of possible scores is 0 to 8 for the stiffness subscale.
Posterior mean change from baseline, 95% CrI was derived using Bayesian mixed model repeated measures. The Bayesian analyses include posterior probabilities instead of p-values, and 95% credible intervals instead of 95% confidence intervals.
measure: Change From Baseline on the WOMAC® Physical Function Subscale
time frame: Baseline, up to Week 8
description: The WOMAC® is a validated instrument that is extensively used to evaluate the response to medications for the treatment of Osteoarthritis pain. There are 17 questions in the physical function subscale, and participants used a 0 to 4 Likert scale to answer each question for the current day: 0 = no difficulty, and 4 = extreme difficulty. The scores for each subscale were calculated by summing the scores of the questions in each respective subscale for each participant at each time point. The range of possible scores is 0 to 68 for the physical function subscale.
Posterior mean change from baseline, 95% CrI was derived using Bayesian mixed model repeated measures. The Bayesian analyses include posterior probabilities instead of p-values, and 95% credible intervals instead of 95% confidence intervals.
measure: Change From Baseline for Overall Improvement as Measured by Patient's Global Impression of Change (PGI)
time frame: Baseline, up to Week 8
description: Patients Global Impression of Change captured the participant's perspective of treatment apart from sub-aspects of the general improvement. This is a numeric scale from 1 to 7: 1 = very much better, and 7 = very much worse.
Posterior mean change from baseline, 95% CrI was derived using Bayesian mixed model repeated measures. The Bayesian analyses include posterior probabilities instead of p-values, and 95% credible intervals instead of 95% confidence intervals.
measure: Change From Baseline for Worst Pain Intensity as Measured by NRS
time frame: Baseline, up to Week 8
description: The NRS was used during the preliminary data entry period and daily throughout the study to describe pain severity. Participants were asked to describe their worst pain over the past 24 hours, on a scale of 0 to 10: 0 = no pain, and 10 = pain as bad as you can imagine.
Posterior mean change from baseline, 95% CrI was derived using Bayesian mixed model repeated measures. The Bayesian analyses include posterior probabilities instead of p-values, and 95% credible intervals instead of 95% confidence intervals.
measure: Change From Baseline on the Visual Analog Scale (VAS) for Pain
time frame: Baseline, up to Week 8
description: VAS was a graphic, single-item scale where participants were asked to describe their pain intensity over the past week, on a scale of 0 to 100: 0 = no pain, and 100 = worst imaginable pain. Participants completed the VAS by placing a line perpendicular to the VAS line at a point that described their pain intensity.
Posterior mean change from baseline, 95% CrI was derived using Bayesian mixed model repeated measures. The Bayesian analyses include posterior probabilities instead of p-values, and 95% credible intervals instead of 95% confidence intervals.
measure: Change From Baseline Assessment to Endpoint on the Sleep Scale From the Medical Outcomes Study (MOS Sleep Scale)
time frame: Baseline, up to Week 8
description: The MOS Sleep Scale consists of 12 questions addressing the past week. Participants reported how often each sleep symptom or problem was present on a 5-point categorical scale ranging from 'all of the time' to 'none of the time.' It includes 12 questions with the first question assessing how long it takes the subject to fall asleep. The second question asks how many hours each night the subject slept. The remaining 10 questions have a range of 6 responses from 1="all of the time" to 6="none of the time". MOS Sleep scale scores range from 0 (min) to 100 (max). The original survey items are converted to a 0 to 100 range (by Converting 1 to 0, 2 to 25, 3 to 50, 4 to 75, and 5 to 100). Higher scores represent worse outcomes.
Posterior mean change from baseline, 95% CrI was derived using Bayesian longitudinal model. The Bayesian analyses include posterior probabilities instead of p-values, and 95% credible intervals instead of 95% confidence intervals.
measure: Total Amount of Rescue Medication Use as Measured by Average Dosage Per Week
time frame: Baseline up to Week 8
description: Total Amount of Rescue Medication Use as Measured by Average Dosage per Week. Posterior mean change from baseline, 95% CrI was derived using Bayesian mixed model repeated measures. The Bayesian analyses include posterior probabilities instead of p-values, and 95% credible intervals instead of 95% confidence intervals.
measure: Change From Baseline on the EuroQol-5D 5 Level Questionnaire (EQ-5D-5L) (United States)
time frame: Baseline, up to Week 8
description: The EQ-5D-5L assessed quality of life based on 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. The participant was asked to 'check the ONE box that best describes your health TODAY,' choosing from 5 options (no problems, slight problems, moderate problems, severe problems, extreme problems) provided under each dimension. The scores in the 5 dimensions were summarized into a health state index score. The health state index value is a single value on a scale from less than 0 to 1 (negative values are valued as worse than dead) with higher scores indicating better health: 0 = a health state equivalent to death, and 1 = perfect health.
Posterior mean change from baseline, 95% CrI was derived using Bayesian mixed model repeated measures. The Bayesian analyses include posterior probabilities instead of p-values, and 95% credible intervals instead of 95% confidence intervals.
arm group label: 750 Mg-500 mg LY3016859
arm group type: Experimental
description: Participants received LY3016859 every 2 weeks with 750 milligram (mg) as starting dose followed by 500 mg intravenous (IV) infusion for a total of 4 doses.
arm group label: Placebo
arm group type: Placebo Comparator
description: Participants received placebo every 2 weeks by IV infusion for a total of 4 doses.
intervention type: Drug
intervention name: LY3016859
description: LY3016859 given IV.
arm group label: 750 Mg-500 mg LY3016859
intervention type: Drug
intervention name: Placebo
description: Placebo given IV.
arm group label: Placebo
criteria: 
gender: All
minimum age: 40 Years
maximum age: N/A
healthy volunteers: No
last name: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM -5 PM Eastern time (UTC/GMT - 5 hours, EST)
role: Study Director
affiliation: Eli Lilly and Company
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country: Puerto Rico
country: United States
url: https://trials.lillytrialguide.com/en-US/trial/6VXLrQld1Oc5hSVgHZh3OP
description: Chronic Pain Master Protocol (CPMP): A Study of LY3016859 in Participants with Osteoarthritis
responsible party type: Sponsor
mesh term: Osteoarthritis
sharing ipd: Yes
ipd description: Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Clinical Study Report (CSR)
ipd time frame: Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.
ipd access criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
ipd url: https://vivli.org/
provided document: 
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participant flow: 
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outcome list: 
reported events: 
certain agreements: 
point of contact: 