<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/NCT02242435</url>
  </required_header>
  <id_info>
    <org_study_id>AP-008</org_study_id>
    <nct_id>NCT02242435</nct_id>
  </id_info>
  <brief_title>A Multiple Injection Study Evaluating Safety and Efficacy of Ampion in Osteoarthritis</brief_title>
  <official_title>A Randomized, Placebo-controlled, Double-blind Study to Evaluate the Safety and Efficacy of Three Intra-articular Injections of Ampion™ (4 mL) Administered Two Weeks Apart in Adults With Pain Due to Osteoarthritis of the Knee</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Ampio Pharmaceuticals. Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Ampio Pharmaceuticals. Inc.</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 will evaluate the efficacy of three intra-articular injections, given 2 weeks&#xD;
      apart, of Ampion™ in Adults with pain due to osteoarthritis of the knee.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      A randomized, placebo-controlled, double-blinded study to evaluate the efficacy and safety of&#xD;
      repeated intra-articular injections of Ampion™ in adult subjects with advanced osteoarthritis&#xD;
      of the knee.&#xD;
&#xD;
      The primary study objective was to evaluate the efficacy and safety from Baseline to Week 20&#xD;
      of 3 Ampion™ 4 mL intra-articular (IA) injections vs saline administered 2 weeks apart in&#xD;
      improving knee pain in subjects suffering from osteoarthritis (OA) of the knee (OAK).&#xD;
&#xD;
      The secondary study objective was to analyze the effect of Ampion 4 mL vs saline on a change&#xD;
      in Patient's Global Assessment (PGA) and knee function from Baseline to Week 20.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 2014</start_date>
  <completion_date type="Actual">May 2015</completion_date>
  <primary_completion_date type="Actual">April 2015</primary_completion_date>
  <phase>Phase 3</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 in Knee Pain</measure>
    <time_frame>Scored at Baseline and 20 Weeks</time_frame>
    <description>Mean Change in WOMAC A Pain (Western Ontario and McMaster Universities Arthritis Index) score from Baseline to 12 weeks. 5-point Likert scale (0=none to 4=extreme). A negative difference constitutes a decrease in pain with a greater negative value indicating a greater reduction in pain.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in Knee Function</measure>
    <time_frame>Scored at Baseline and 20 Weeks</time_frame>
    <description>Mean change in WOMAC C function score (Western Ontario and McMaster Universities Arthritis Index) from Baseline to 12 weeks. 5-point Likert scale indicating limitation of function (0=none to 4=extreme). A greater negative value indicates a improvement in function.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">342</enrollment>
  <condition>Osteoarthritis of the Knee</condition>
  <arm_group>
    <arm_group_label>Ampion 4ml dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>4 mL intra-articular injection of Ampion</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo Solution</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>4 mL placebo intra-articular injection</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>4 mL injection of Ampion</intervention_name>
    <description>4 mL injection of Ampion</description>
    <arm_group_label>Ampion 4ml dose</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>4 mL Injection of Placebo</intervention_name>
    <arm_group_label>Placebo Solution</arm_group_label>
    <other_name>Saline</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Able to provide written informed consent to participate in the study.&#xD;
&#xD;
          2. Willing and able to comply with all study requirements and instructions of the site&#xD;
             study staff.&#xD;
&#xD;
          3. Male or female, 40 years to 85 years old (inclusive).&#xD;
&#xD;
          4. Must be ambulatory.&#xD;
&#xD;
          5. Index knee must be symptomatic for greater than 6 months with a clinical diagnosis of&#xD;
             OA and supported by radiological evidence (x-ray) acquired at screening and assessed&#xD;
             by a central reader. Subjects must have a Kellgren Lawrence Grade of III or IV for&#xD;
             inclusion in the study.&#xD;
&#xD;
          6. Moderate to moderately-severe OA pain in the index knee (rating of at least 1.5 on the&#xD;
             WOMAC® Index 3.1 5-point Likert Pain Subscale) assessed at screening and confirmed at&#xD;
             randomization.&#xD;
&#xD;
          7. Moderate to moderately-severe OA pain in the index knee (even if chronic doses of&#xD;
             non-steroidal anti-inflammatory drug [NSAID], which have not changed in the 4 weeks&#xD;
             prior to screening, have been/are being used).&#xD;
&#xD;
          8. No analgesia taken 24 hours before efficacy measure.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. As a result of medical review and screening investigation, the Principal Investigator&#xD;
             considers the subject unfit for the study.&#xD;
&#xD;
          2. Previous Ampion™ injection in the index knee.&#xD;
&#xD;
          3. Known clinically significant liver abnormality (e.g., cirrhosis, transplant, etc).&#xD;
&#xD;
          4. A history of allergic reactions to human albumin (reaction to non-human albumin such&#xD;
             as egg albumin is not an exclusion criterion).&#xD;
&#xD;
          5. A history of allergic reactions to excipients in 5% human albumin (N-acetyltryptophan,&#xD;
             sodium caprylate).&#xD;
&#xD;
          6. Presence of tense effusions in the index knee.&#xD;
&#xD;
          7. Inflammatory or crystal arthropathies, acute fractures, history of aseptic necrosis or&#xD;
             joint replacement in the index knee, as assessed locally by the Principal&#xD;
             Investigator.&#xD;
&#xD;
          8. Isolated patella femoral syndrome, also known as chondromalacia, in the index knee.&#xD;
&#xD;
          9. Any other disease or condition interfering with the free use and evaluation of the&#xD;
             index knee for the duration of the trial (e.g., cancer, congenital defects, spine OA).&#xD;
&#xD;
         10. Major injury to the index knee within the 12 months prior to screening.&#xD;
&#xD;
         11. Severe hip OA ipsilateral to the index knee.&#xD;
&#xD;
         12. Any pain that could interfere with the assessment of index knee pain (e.g., pain in&#xD;
             any other part of the lower extremities, pain radiating to the knee).&#xD;
&#xD;
         13. Any pharmacological or non-pharmacological treatment targeting OA started or changed&#xD;
             during the 4 weeks prior to treatment or likely to be changed during the duration of&#xD;
             the study.&#xD;
&#xD;
         14. Use of the following medications are exclusionary:&#xD;
&#xD;
               1. IA injected pain medications in the study knee during the study;&#xD;
&#xD;
               2. Analgesics containing opioids. NSAIDs may be continued at levels preceding the&#xD;
                  study and acetaminophen is available as a rescue medication during the study from&#xD;
                  the provided supply;&#xD;
&#xD;
               3. Topical treatment on osteoarthritis index knee during the study;&#xD;
&#xD;
               4. Significant anticoagulant therapy (e.g., Heparin or Lovenox) during the study&#xD;
                  (treatment such as Aspirin and Plavix are allowed);&#xD;
&#xD;
               5. Systemic treatments that may interfere with safety or efficacy assessments during&#xD;
                  the study;&#xD;
&#xD;
               6. Immunosuppressants;&#xD;
&#xD;
               7. Use of corticosteroids &gt; 10 mg prednisolone equivalent per day (if ≤ 10 mg&#xD;
                  prednisolone, the dose must be stable).&#xD;
&#xD;
         15. Any human albumin treatment in the 3 months before randomization.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Howard Levy, M.D.</last_name>
    <role>Study Director</role>
    <affiliation>Ampio Pharmaceuticals. Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Ampio Pharmaceuticals, Inc.</name>
      <address>
        <city>Englewood</city>
        <state>Colorado</state>
        <zip>80112</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2022</verification_date>
  <study_first_submitted>September 15, 2014</study_first_submitted>
  <study_first_submitted_qc>September 16, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 17, 2014</study_first_posted>
  <results_first_submitted>August 4, 2022</results_first_submitted>
  <results_first_submitted_qc>August 4, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">August 29, 2022</results_first_posted>
  <disposition_first_submitted>June 18, 2019</disposition_first_submitted>
  <disposition_first_submitted_qc>June 18, 2019</disposition_first_submitted_qc>
  <disposition_first_posted type="Actual">June 20, 2019</disposition_first_posted>
  <last_update_submitted>August 29, 2022</last_update_submitted>
  <last_update_submitted_qc>August 29, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">September 15, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Osteoarthritis</keyword>
  <keyword>osteoarthritis of the knee</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Osteoarthritis</mesh_term>
    <mesh_term>Osteoarthritis, Knee</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Recruitment of subjects occurred in medical clinics during the months of September, October, and November 2014.</recruitment_details>
      <pre_assignment_details>No pharmacological or non-pharmacological treatment targeting osteoarthritis (OA) started or changed during the 4 weeks prior to randomization or likely to be changed during the duration of the study.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Ampion 4 mL</title>
          <description>4 mL intra-articular injection of Ampion&#xD;
Ampion &lt;5 kilodalton (kDa) ultrafiltrate of 5% human serum albumin: 4 mL intra-articular injection of Ampion</description>
        </group>
        <group group_id="P2">
          <title>Placebo 4 mL</title>
          <description>4 mL placebo intra-articular injection&#xD;
Placebo: Saline</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="172"/>
                <participants group_id="P2" count="170"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="152"/>
                <participants group_id="P2" count="154"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="20"/>
                <participants group_id="P2" count="16"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="4"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <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="13"/>
                <participants group_id="P2" count="8"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <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="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Physician Decision</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>Intent to Treat (ITT)</population>
      <group_list>
        <group group_id="B1">
          <title>Ampion 4 mL</title>
          <description>4 mL intra-articular injection of Ampion&#xD;
Ampion &lt;5 kDa ultrafiltrate of 5% human serum albumin</description>
        </group>
        <group group_id="B2">
          <title>Placebo 4 mL</title>
          <description>4 mL placebo intra-articular injection&#xD;
Placebo: Saline</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="172"/>
            <count group_id="B2" value="170"/>
            <count group_id="B3" value="342"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <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="9.1"/>
                    <measurement group_id="B2" value="63.2" spread="9.5"/>
                    <measurement group_id="B3" value="63.2" spread="9.3"/>
                  </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="93"/>
                    <measurement group_id="B2" value="105"/>
                    <measurement group_id="B3" value="198"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="79"/>
                    <measurement group_id="B2" value="65"/>
                    <measurement group_id="B3" value="144"/>
                  </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="12"/>
                    <measurement group_id="B3" value="23"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="161"/>
                    <measurement group_id="B2" value="158"/>
                    <measurement group_id="B3" value="319"/>
                  </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="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                  </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="2"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="22"/>
                    <measurement group_id="B2" value="36"/>
                    <measurement group_id="B3" value="58"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="146"/>
                    <measurement group_id="B2" value="130"/>
                    <measurement group_id="B3" value="276"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                  </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>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="172"/>
                    <measurement group_id="B2" value="170"/>
                    <measurement group_id="B3" value="342"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Weight (kg)</title>
          <units>kg</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="96.2" spread="23.8"/>
                    <measurement group_id="B2" value="96.4" spread="22.5"/>
                    <measurement group_id="B3" value="96.3" spread="23.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>BMI (kg/m^2)</title>
          <units>kg/m^2</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="34.3" spread="7.5"/>
                    <measurement group_id="B2" value="34.9" spread="8.0"/>
                    <measurement group_id="B3" value="34.6" spread="7.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Kellgren-Lawrence (KL) Grade</title>
          <description>Kellgren-Lawrence grading is based on the radiologic features of osteoarthritis.&#xD;
Ann Rheum Dis. 1957;16:494-502.&#xD;
Grade III (Moderate): Moderate osteophytes, definite joint space narrowing, some sclerosis, possible bone-end deformity.&#xD;
Grade IV (Severe): Large osteophytes, marked joint space narrowing, severe sclerosis, definite bone ends deformity.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Kellgren-Lawrence Grade III</title>
                  <measurement_list>
                    <measurement group_id="B1" value="50"/>
                    <measurement group_id="B2" value="64"/>
                    <measurement group_id="B3" value="114"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Kellgren-Lawrence Grade IV</title>
                  <measurement_list>
                    <measurement group_id="B1" value="122"/>
                    <measurement group_id="B2" value="106"/>
                    <measurement group_id="B3" value="228"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>WOMAC Pain</title>
          <description>The Western Ontario and McMaster Universities Arthritis Index (WOMAC) 3.1 evaluates Pain (5 items): during walking, using stairs, in bed, sitting or lying, and standing upright.&#xD;
Subjects respond to each subscale by using a 5-point Likert score. (0=none; 1=mild; 2=moderate; 3=severe; 4=extreme). Mean of the 5 scores constitutes the Baseline Pain Score.&#xD;
The minimum score on this scale is 0, and the maximum score is 4. Higher scores are indicative of higher levels of self-reported pain.</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="2.51" spread="0.57"/>
                    <measurement group_id="B2" value="2.57" spread="0.61"/>
                    <measurement group_id="B3" value="2.54" spread="0.59"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>WOMAC Function</title>
          <description>WOMAC 3.1 evaluates Physical Function (17 items): using stairs, rising from sitting, standing, bending, walking, getting in/out of a car, shopping, putting on/taking off socks, rising from bed, lying in bed, getting in/out of bath, sitting, getting on/off toilet, heavy/light domestic duties.&#xD;
Subjects respond to each by using a 5-point Likert score. (0=none; 1=mild; 2=moderate; 3=severe; 4=extreme). Mean of the 17 scores constitutes the Baseline Function Score. Minimum score is 0; maximum is 4.&#xD;
Higher scores indicate of higher levels of limitations of self-reported physical function.</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="2.51" spread="0.63"/>
                    <measurement group_id="B2" value="2.59" spread="0.61"/>
                    <measurement group_id="B3" value="2.55" spread="0.62"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change in Knee Pain</title>
        <description>Mean Change in WOMAC A Pain (Western Ontario and McMaster Universities Arthritis Index) score from Baseline to 12 weeks. 5-point Likert scale (0=none to 4=extreme). A negative difference constitutes a decrease in pain with a greater negative value indicating a greater reduction in pain.</description>
        <time_frame>Scored at Baseline and 20 Weeks</time_frame>
        <population>Intent to Treat (ITT)</population>
        <group_list>
          <group group_id="O1">
            <title>Ampion 4 mL Injection</title>
            <description>4 mL intra-articular injection of Ampion&#xD;
Ampion: &lt;5 kDa ultrafiltrate of 5% human serum albumin</description>
          </group>
          <group group_id="O2">
            <title>Placebo 4 mL Injection</title>
            <description>4 mL placebo intra-articular injection&#xD;
Placebo: Saline</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Knee Pain</title>
          <description>Mean Change in WOMAC A Pain (Western Ontario and McMaster Universities Arthritis Index) score from Baseline to 12 weeks. 5-point Likert scale (0=none to 4=extreme). A negative difference constitutes a decrease in pain with a greater negative value indicating a greater reduction in pain.</description>
          <population>Intent to Treat (ITT)</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="172"/>
                <count group_id="O2" value="170"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.96" lower_limit="-1.09" upper_limit="-0.82"/>
                    <measurement group_id="O2" value="-1.10" lower_limit="-1.24" upper_limit="-0.95"/>
                  </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>
            <p_value>0.26</p_value>
            <p_value_desc>Adjusted for baseline WOMAC score.</p_value_desc>
            <method>ANCOVA</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Knee Function</title>
        <description>Mean change in WOMAC C function score (Western Ontario and McMaster Universities Arthritis Index) from Baseline to 12 weeks. 5-point Likert scale indicating limitation of function (0=none to 4=extreme). A greater negative value indicates a improvement in function.</description>
        <time_frame>Scored at Baseline and 20 Weeks</time_frame>
        <population>Intent to Treat (ITT)</population>
        <group_list>
          <group group_id="O1">
            <title>Ampion 4 mL Injection</title>
            <description>4 mL intra-articular injection of Ampion&#xD;
Ampion: &lt;5 kDa ultrafiltrate of 5% human serum albumin</description>
          </group>
          <group group_id="O2">
            <title>Placebo 4 mL Injection</title>
            <description>4 mL placebo intra-articular injection&#xD;
Placebo: Saline</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Knee Function</title>
          <description>Mean change in WOMAC C function score (Western Ontario and McMaster Universities Arthritis Index) from Baseline to 12 weeks. 5-point Likert scale indicating limitation of function (0=none to 4=extreme). A greater negative value indicates a improvement in function.</description>
          <population>Intent to Treat (ITT)</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="172"/>
                <count group_id="O2" value="170"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.94" lower_limit="-1.08" upper_limit="-0.81"/>
                    <measurement group_id="O2" value="-1.08" lower_limit="-1.22" upper_limit="-0.94"/>
                  </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>
            <p_value>0.30</p_value>
            <p_value_desc>Adjustment for baseline WOMAC score.</p_value_desc>
            <method>ANCOVA</method>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>24 Weeks</time_frame>
      <desc>Patients will be followed for the occurrence of Adverse Events (AEs) from Baseline through Week 24.</desc>
      <group_list>
        <group group_id="E1">
          <title>Ampion 4 mL</title>
          <description>4 mL intra-articular injection of Ampion&#xD;
Ampion &lt;5 kDa ultrafiltrate of 5% human serum albumin: 4 mL intra-articular injection of Ampion</description>
        </group>
        <group group_id="E2">
          <title>Placebo 4 mL</title>
          <description>4 mL placebo intra-articular injection&#xD;
Placebo: Saline</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA (16.0)</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="172"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="170"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="172"/>
                <counts group_id="E2" subjects_affected="11" subjects_at_risk="170"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Angina Unstable</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="172"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="170"/>
              </event>
              <event>
                <sub_title>Atrial Fibrillation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="172"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="170"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Abcess Limb</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="172"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="170"/>
              </event>
              <event>
                <sub_title>Gastroenteritis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="172"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="170"/>
              </event>
              <event>
                <sub_title>Influenza</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="172"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="170"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Incisional Hernia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="172"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="170"/>
              </event>
              <event>
                <sub_title>Injury</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="172"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="170"/>
              </event>
              <event>
                <sub_title>Joint Injury</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="172"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="170"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="172"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="170"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Plasma Cell Myeloma</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="172"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="170"/>
              </event>
              <event>
                <sub_title>Salivary Gland Cancer</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="172"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="170"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Transient Ischaemic Attack</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="172"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="170"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="172"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="170"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Angioedema</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="172"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="170"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>2</frequency_threshold>
        <default_vocab>MedDRA (16.0)</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="107" subjects_at_risk="172"/>
                <counts group_id="E2" subjects_affected="125" subjects_at_risk="170"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="172"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="170"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Injection Site Bruising</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="172"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="170"/>
              </event>
              <event>
                <sub_title>Injection Site Pain</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="172"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="170"/>
              </event>
              <event>
                <sub_title>Injection Site Swelling</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="172"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="170"/>
              </event>
              <event>
                <sub_title>Oedema Peripheral</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="172"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="170"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="172"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="170"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Bronchitis</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="172"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="170"/>
              </event>
              <event>
                <sub_title>Gastroenteritis</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="172"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="170"/>
              </event>
              <event>
                <sub_title>Influenza</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="172"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="170"/>
              </event>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="172"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="170"/>
              </event>
              <event>
                <sub_title>Respiratory Tract Infection Viral</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="172"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="170"/>
              </event>
              <event>
                <sub_title>Sinusitis</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="172"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="170"/>
              </event>
              <event>
                <sub_title>Upper Respiratory Tract Infection</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="172"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="170"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Contusion</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="172"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="170"/>
              </event>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="172"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="170"/>
              </event>
              <event>
                <sub_title>Joint Injury</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="172"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="170"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" subjects_affected="19" subjects_at_risk="172"/>
                <counts group_id="E2" subjects_affected="21" subjects_at_risk="170"/>
              </event>
              <event>
                <sub_title>Back Pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="172"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="170"/>
              </event>
              <event>
                <sub_title>Joint Stiffness</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="172"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="170"/>
              </event>
              <event>
                <sub_title>Joint Swelling</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="172"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="170"/>
              </event>
              <event>
                <sub_title>Pain in Extremity</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="172"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="170"/>
              </event>
              <event>
                <sub_title>Plantar Fasciitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="172"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="170"/>
              </event>
              <event>
                <sub_title>Bursitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="172"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="170"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="172"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="170"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="172"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="170"/>
              </event>
              <event>
                <sub_title>Asthma</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="172"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="170"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="172"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="170"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="172"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="170"/>
              </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>The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Dr. Howard Levy / Chief Medical Officer</name_or_title>
      <organization>Ampio Pharmaceuticals</organization>
      <phone>7204376500</phone>
      <email>clinicaltrials@ampiopharma.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/NCT02242435
org study id: AP-008
nct id: NCT02242435
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This study will evaluate the efficacy of three intra-articular injections, given 2 weeks
      apart, of Ampion™ in Adults with pain due to osteoarthritis of the knee.
A randomized, placebo-controlled, double-blinded study to evaluate the efficacy and safety of
      repeated intra-articular injections of Ampion™ in adult subjects with advanced osteoarthritis
      of the knee.

      The primary study objective was to evaluate the efficacy and safety from Baseline to Week 20
      of 3 Ampion™ 4 mL intra-articular (IA) injections vs saline administered 2 weeks apart in
      improving knee pain in subjects suffering from osteoarthritis (OA) of the knee (OAK).

      The secondary study objective was to analyze the effect of Ampion 4 mL vs saline on a change
      in Patient's Global Assessment (PGA) and knee function from Baseline to Week 20.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Change in Knee Pain
time frame: Scored at Baseline and 20 Weeks
description: Mean Change in WOMAC A Pain (Western Ontario and McMaster Universities Arthritis Index) score from Baseline to 12 weeks. 5-point Likert scale (0=none to 4=extreme). A negative difference constitutes a decrease in pain with a greater negative value indicating a greater reduction in pain.
measure: Change in Knee Function
time frame: Scored at Baseline and 20 Weeks
description: Mean change in WOMAC C function score (Western Ontario and McMaster Universities Arthritis Index) from Baseline to 12 weeks. 5-point Likert scale indicating limitation of function (0=none to 4=extreme). A greater negative value indicates a improvement in function.
arm group label: Ampion 4ml dose
arm group type: Experimental
description: 4 mL intra-articular injection of Ampion
arm group label: Placebo Solution
arm group type: Placebo Comparator
description: 4 mL placebo intra-articular injection
intervention type: Biological
intervention name: 4 mL injection of Ampion
description: 4 mL injection of Ampion
arm group label: Ampion 4ml dose
intervention type: Drug
intervention name: 4 mL Injection of Placebo
arm group label: Placebo Solution
other name: Saline
criteria: 
gender: All
minimum age: 40 Years
maximum age: 85 Years
healthy volunteers: No
last name: Howard Levy, M.D.
role: Study Director
affiliation: Ampio Pharmaceuticals. Inc.
facility: 
country: United States
responsible party type: Sponsor
mesh term: Osteoarthritis
mesh term: Osteoarthritis, Knee
sharing ipd: No
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 