<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/NCT04457960</url>
  </required_header>
  <id_info>
    <org_study_id>CR108764</org_study_id>
    <secondary_id>2018-003743-29</secondary_id>
    <secondary_id>66525433IBD1001</secondary_id>
    <nct_id>NCT04457960</nct_id>
  </id_info>
  <brief_title>A Study of JNJ-66525433 in Healthy Participants and Participants With Ulcerative Colitis</brief_title>
  <official_title>A Phase 1, Randomized, Double-blind, Placebo-controlled, Single and Multiple Ascending Dose Study in Healthy Participants and Multiple Dose Study in Participants With Ulcerative Colitis to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of JNJ-66525433</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Janssen Research &amp; Development, LLC</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Janssen Research &amp; Development, LLC</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>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to evaluate safety and tolerability of JNJ 66525433 compared&#xD;
      with placebo after administration of: 1) single ascending oral doses of JNJ 66525433&#xD;
      administered to healthy participants (Part 1), 2) multiple, ascending oral doses of JNJ&#xD;
      66525433, administered to healthy participants once daily over 14 consecutive days (Part 2),&#xD;
      and 3) multiple oral doses of JNJ 66525433, administered once daily over 14 consecutive and&#xD;
      once daily over 42 consecutive days in participants with ulcerative colitis (UC) (Part 3).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Sponsor Decision.&#xD;
  </why_stopped>
  <start_date type="Actual">July 1, 2020</start_date>
  <completion_date type="Actual">October 13, 2021</completion_date>
  <primary_completion_date type="Actual">October 13, 2021</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Part 1, 2 and 3: Number of Participants with Treatment-emergent Adverse Events (TEAEs) as a Measure of Safety and Tolerability</measure>
    <time_frame>Up to 224 Days</time_frame>
    <description>An adverse event (AE) is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. Any AE occurring at or after the initial administration of study intervention through the day of last dose plus 30 days will be considered as TEAE.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Part 1, 2 and 3: Number of Participants with Vital Sign Abnormalities</measure>
    <time_frame>Up to 224 Days</time_frame>
    <description>Number of participants with vital sign abnormalities (temperature), pulse/heart rate, respiratory rate and blood pressure) will be reported.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Part 1, 2 and 3: Number of Participants with Physical Examination Abnormalities</measure>
    <time_frame>Up to 224 Days</time_frame>
    <description>Number of participants with physical examination abnormalities will be reported.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Part 1, 2 and 3: Number of Participants with Hematology Laboratory Abnormalities</measure>
    <time_frame>Up to 224 Days</time_frame>
    <description>Number of participants with hematology laboratory abnormalities will be reported.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Part 1, 2 and 3: Number of Participants with Chemistry Laboratory Abnormalities</measure>
    <time_frame>Up to 224 Days</time_frame>
    <description>Number of participants with chemistry laboratory abnormalities will be reported.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Part 1, 2 and 3: Number of Participants with Urinalysis Laboratory Abnormalities</measure>
    <time_frame>Up to 224 Days</time_frame>
    <description>Number of participants with abnormalities in urinalysis will be reported.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Part 2 and 3: Number of Participants with Abnormalities in High Sensitivity C- Reactive Protein (hs-CRP)</measure>
    <time_frame>Up to 224 Days</time_frame>
    <description>Number of participants with abnormalities in hs-CRP will be reported using a validated, high sensitivity CRP assay.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Part 2 and 3: Number of Participants with Abnormalities in Fecal Calprotectin</measure>
    <time_frame>Up to 224 Days</time_frame>
    <description>Assays for fecal calprotectin will be performed using a validated method.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Part 2 and 3: Incidence of Enteric Pathogens in Stool Samples</measure>
    <time_frame>Up to 224 Days</time_frame>
    <description>Stool culture and Clostridium difficile toxin assay will be used for enteric pathogen assessment.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Part 1, 2 and 3: Number of Participants with Electrocardiogram (ECG) Abnormalities</measure>
    <time_frame>Up to 224 Days</time_frame>
    <description>Number of participants with ECG abnormalities will be reported.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Part 1, 2 and 3: Plasma Concentrations of JNJ-66525433</measure>
    <time_frame>Up to 224 Days</time_frame>
    <description>Plasma concentrations of JNJ-66525433 will be reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 1: Plasma Concentrations of JNJ-66525433 After Fasted or Fed Dosing</measure>
    <time_frame>Up to Day 14</time_frame>
    <description>Plasma concentrations of JNJ-66525433 after fasted or fed dosing will be reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 3: Mayo Score</measure>
    <time_frame>Up to Day 84</time_frame>
    <description>Mayo scoring system is used for assessment of ulcerative colitis activity. The Mayo score consists of 4 subscores (stool frequency, rectal bleeding, physician's global assessment, and endoscopy findings) each ranges from 0 to 3. The Mayo score is calculated as the sum of these 4 subscores and can range between 0 and 12, where higher score indicates severe disease.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 3: Partial Mayo Score</measure>
    <time_frame>Up to Day 70</time_frame>
    <description>Partial Mayo score is calculated as the sum of 3 subscores (stool frequency, rectal bleeding, and physician's global assessment) and ranges from 0 to 9 points. Higher score indicates severe disease.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 3: Endoscopic Subscore</measure>
    <time_frame>Up to Day 84</time_frame>
    <description>Endoscopy sub-score ranges from 0 to 3 where; 0 = normal or inactive disease; 1 = mild disease (erythema, decreased vascular pattern, mild friability); 2 = moderate disease (marked erythema, absent vascular pattern, friability, erosions); 3 = severe disease (spontaneous bleeding, ulceration).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 3: Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score</measure>
    <time_frame>Days 1, 7, 14, 28, 43, 70 and 84</time_frame>
    <description>IBDQ18 is a validated, 32-item, self-reported questionnaire for participants with inflammatory bowel disease (IBD) that will be used to evaluate the disease-specific health-related quality of life across 4 dimensional scores: bowel symptoms (loose stools, abdominal pain), systemic functions (fatigue, altered sleep pattern), social function (work attendance, need to cancel social events), and emotional function (anger, depression, irritability). Scores range from 32 to 224, with higher scores indicating better outcomes.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 2 and 3: Target Engagement of Messenger Ribonucleic Acid (mRNA) Levels</measure>
    <time_frame>Up to 182 Days</time_frame>
    <description>Levels of mRNA knockdown will be reported to assess target engagement in biopsy tissue by dose level over time.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 2 and 3: Tissue Biopsy JNJ-66525433 Concentrations</measure>
    <time_frame>Up to 182 Days</time_frame>
    <description>Tissue biopsy concentrations of JNJ-66525433 will be reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Plasma Concentrations of JNJ-66525433 After Two Meal Timing Conditions</measure>
    <time_frame>Up to 22 Days</time_frame>
    <description>Plasma concentrations of JNJ-66525433 after two meal timing condition (fed state to modified fasted state) will be reported (if conducted).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Faecal Concentrations of JNJ-66525433 After Two Meal Timing Conditions</measure>
    <time_frame>Predose, up to 120 hours postdose</time_frame>
    <description>Stool assessment will be done to characterize the presence of JNJ-66525433 after two meal timing conditions (fed state to modified fasted state) will be reported (if conducted).</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">82</enrollment>
  <condition>Healthy</condition>
  <condition>Colitis, Ulcerative</condition>
  <arm_group>
    <arm_group_label>JNJ-66525433</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive JNJ-66525433 in increasing dose level 1 to dose level 4 in Parts 1, 2, and dose level 3 in part 3.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants will receive matching placebo in Parts 1, 2 and 3.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>JNJ-66525433</intervention_name>
    <description>Participants will receive JNJ-66525433 oral capsules.</description>
    <arm_group_label>JNJ-66525433</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Participants will receive matching placebo oral capsules.</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        For Part 1 and Part 2, healthy volunteers&#xD;
&#xD;
          -  Have a body mass index (BMI) between 18 and 30 kilogram per meter square (kg/m^2) (BMI&#xD;
             = weight/height), inclusive, and a body weight of no less than 50 kilogram (kg) and&#xD;
             maximum weight of 100 kg&#xD;
&#xD;
          -  Have normal bowel movements, ranging from 1 to 3 times daily to every other day and&#xD;
             have normal consistencies according to the Bristol Stool Scale, ranging from 3 to 5 at&#xD;
             admission&#xD;
&#xD;
        For Part 3, participants with ulcerative colitis (UC)&#xD;
&#xD;
          -  Have a clinical diagnosis of UC at least 3 months before screening&#xD;
&#xD;
          -  Have moderately to severely active UC, defined as a Week 0 mayo score of 6 to 12,&#xD;
             inclusive, based on central read of the video endoscopy performed during the screening&#xD;
&#xD;
          -  Have a greater than or equal to (&gt;=) 2 endoscopy subscore of the Week 0 mayo score&#xD;
             based on central read of the video endoscopy performed during the screening&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        For Part 1 and Part 2, healthy volunteers&#xD;
&#xD;
          -  History of liver or renal insufficiency, significant cardiac, vascular, pulmonary,&#xD;
             gastrointestinal, endocrine, neurologic, hematologic, rheumatologic, psychiatric, or&#xD;
             metabolic disturbances&#xD;
&#xD;
          -  Known allergies, hypersensitivity, or intolerance to antisense oligonucleotides,&#xD;
             JNJ-66525433 or its excipients&#xD;
&#xD;
        For Part 3, participants with UC&#xD;
&#xD;
          -  Has UC limited to the rectum only or to &lt;20 centimeter (cm) of the colon evaluated by&#xD;
             endoscopy at screening&#xD;
&#xD;
          -  Presence of a stoma&#xD;
&#xD;
          -  Presence or history of a fistula at any time&#xD;
&#xD;
        COVID-related&#xD;
&#xD;
          -  If a participant is excluded due to recent Coronavirus disease (COVID-19) related&#xD;
             features, the reason for screen failure should be documented in the case report form&#xD;
             under the exclusion criterion of having a condition for which participation would not&#xD;
             be in the participant's interest or could confound study assessments&#xD;
&#xD;
          -  The field of COVID-related testing (for presence of, and immunity to, the severe acute&#xD;
             respiratory syndrome coronavirus 2 [SARS-CoV-2] virus) is rapidly evolving. Additional&#xD;
             testing may be performed as part of screening and/or during the study if deemed&#xD;
             necessary by the investigator and in accordance with current regulations / guidance&#xD;
             from authorities / standards of care&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Janssen Research &amp; Development, LLC Clinical Trial</last_name>
    <role>Study Director</role>
    <affiliation>Janssen Research &amp; Development, LLC</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Charité Research Organisation GmbH</name>
      <address>
        <city>Berlin</city>
        <zip>10117</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <removed_countries>
    <country>Georgia</country>
    <country>Moldova, Republic of</country>
  </removed_countries>
  <verification_date>December 2021</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 7, 2020</study_first_posted>
  <last_update_submitted>December 29, 2021</last_update_submitted>
  <last_update_submitted_qc>December 29, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">January 12, 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>Colitis</mesh_term>
    <mesh_term>Colitis, Ulcerative</mesh_term>
    <mesh_term>Ulcer</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>The data sharing policy of the Janssen Pharmaceutical Companies of Johnson &amp; Johnson is available at www.janssen.com/clinical-trials/transparency.&#xD;
As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu</ipd_description>
    <ipd_url>https://www.janssen.com/clinical-trials/transparency</ipd_url>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</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/NCT04457960
org study id: CR108764
secondary id: 2018-003743-29
secondary id: 66525433IBD1001
nct id: NCT04457960
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
The purpose of this study is to evaluate safety and tolerability of JNJ 66525433 compared
      with placebo after administration of: 1) single ascending oral doses of JNJ 66525433
      administered to healthy participants (Part 1), 2) multiple, ascending oral doses of JNJ
      66525433, administered to healthy participants once daily over 14 consecutive days (Part 2),
      and 3) multiple oral doses of JNJ 66525433, administered once daily over 14 consecutive and
      once daily over 42 consecutive days in participants with ulcerative colitis (UC) (Part 3).
allocation: Randomized
intervention model: Sequential Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Part 1, 2 and 3: Number of Participants with Treatment-emergent Adverse Events (TEAEs) as a Measure of Safety and Tolerability
time frame: Up to 224 Days
description: An adverse event (AE) is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. Any AE occurring at or after the initial administration of study intervention through the day of last dose plus 30 days will be considered as TEAE.
measure: Part 1, 2 and 3: Number of Participants with Vital Sign Abnormalities
time frame: Up to 224 Days
description: Number of participants with vital sign abnormalities (temperature), pulse/heart rate, respiratory rate and blood pressure) will be reported.
measure: Part 1, 2 and 3: Number of Participants with Physical Examination Abnormalities
time frame: Up to 224 Days
description: Number of participants with physical examination abnormalities will be reported.
measure: Part 1, 2 and 3: Number of Participants with Hematology Laboratory Abnormalities
time frame: Up to 224 Days
description: Number of participants with hematology laboratory abnormalities will be reported.
measure: Part 1, 2 and 3: Number of Participants with Chemistry Laboratory Abnormalities
time frame: Up to 224 Days
description: Number of participants with chemistry laboratory abnormalities will be reported.
measure: Part 1, 2 and 3: Number of Participants with Urinalysis Laboratory Abnormalities
time frame: Up to 224 Days
description: Number of participants with abnormalities in urinalysis will be reported.
measure: Part 2 and 3: Number of Participants with Abnormalities in High Sensitivity C- Reactive Protein (hs-CRP)
time frame: Up to 224 Days
description: Number of participants with abnormalities in hs-CRP will be reported using a validated, high sensitivity CRP assay.
measure: Part 2 and 3: Number of Participants with Abnormalities in Fecal Calprotectin
time frame: Up to 224 Days
description: Assays for fecal calprotectin will be performed using a validated method.
measure: Part 2 and 3: Incidence of Enteric Pathogens in Stool Samples
time frame: Up to 224 Days
description: Stool culture and Clostridium difficile toxin assay will be used for enteric pathogen assessment.
measure: Part 1, 2 and 3: Number of Participants with Electrocardiogram (ECG) Abnormalities
time frame: Up to 224 Days
description: Number of participants with ECG abnormalities will be reported.
measure: Part 1, 2 and 3: Plasma Concentrations of JNJ-66525433
time frame: Up to 224 Days
description: Plasma concentrations of JNJ-66525433 will be reported.
measure: Part 1: Plasma Concentrations of JNJ-66525433 After Fasted or Fed Dosing
time frame: Up to Day 14
description: Plasma concentrations of JNJ-66525433 after fasted or fed dosing will be reported.
measure: Part 3: Mayo Score
time frame: Up to Day 84
description: Mayo scoring system is used for assessment of ulcerative colitis activity. The Mayo score consists of 4 subscores (stool frequency, rectal bleeding, physician's global assessment, and endoscopy findings) each ranges from 0 to 3. The Mayo score is calculated as the sum of these 4 subscores and can range between 0 and 12, where higher score indicates severe disease.
measure: Part 3: Partial Mayo Score
time frame: Up to Day 70
description: Partial Mayo score is calculated as the sum of 3 subscores (stool frequency, rectal bleeding, and physician's global assessment) and ranges from 0 to 9 points. Higher score indicates severe disease.
measure: Part 3: Endoscopic Subscore
time frame: Up to Day 84
description: Endoscopy sub-score ranges from 0 to 3 where; 0 = normal or inactive disease; 1 = mild disease (erythema, decreased vascular pattern, mild friability); 2 = moderate disease (marked erythema, absent vascular pattern, friability, erosions); 3 = severe disease (spontaneous bleeding, ulceration).
measure: Part 3: Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score
time frame: Days 1, 7, 14, 28, 43, 70 and 84
description: IBDQ18 is a validated, 32-item, self-reported questionnaire for participants with inflammatory bowel disease (IBD) that will be used to evaluate the disease-specific health-related quality of life across 4 dimensional scores: bowel symptoms (loose stools, abdominal pain), systemic functions (fatigue, altered sleep pattern), social function (work attendance, need to cancel social events), and emotional function (anger, depression, irritability). Scores range from 32 to 224, with higher scores indicating better outcomes.
measure: Part 2 and 3: Target Engagement of Messenger Ribonucleic Acid (mRNA) Levels
time frame: Up to 182 Days
description: Levels of mRNA knockdown will be reported to assess target engagement in biopsy tissue by dose level over time.
measure: Part 2 and 3: Tissue Biopsy JNJ-66525433 Concentrations
time frame: Up to 182 Days
description: Tissue biopsy concentrations of JNJ-66525433 will be reported.
measure: Plasma Concentrations of JNJ-66525433 After Two Meal Timing Conditions
time frame: Up to 22 Days
description: Plasma concentrations of JNJ-66525433 after two meal timing condition (fed state to modified fasted state) will be reported (if conducted).
measure: Faecal Concentrations of JNJ-66525433 After Two Meal Timing Conditions
time frame: Predose, up to 120 hours postdose
description: Stool assessment will be done to characterize the presence of JNJ-66525433 after two meal timing conditions (fed state to modified fasted state) will be reported (if conducted).
arm group label: JNJ-66525433
arm group type: Experimental
description: Participants will receive JNJ-66525433 in increasing dose level 1 to dose level 4 in Parts 1, 2, and dose level 3 in part 3.
arm group label: Placebo
arm group type: Placebo Comparator
description: Participants will receive matching placebo in Parts 1, 2 and 3.
intervention type: Drug
intervention name: JNJ-66525433
description: Participants will receive JNJ-66525433 oral capsules.
arm group label: JNJ-66525433
intervention type: Drug
intervention name: Placebo
description: Participants will receive matching placebo oral capsules.
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Janssen Research & Development, LLC Clinical Trial
role: Study Director
affiliation: Janssen Research & Development, LLC
facility: 
country: Germany
country: Georgia
country: Moldova, Republic of
responsible party type: Sponsor
mesh term: Colitis
mesh term: Colitis, Ulcerative
mesh term: Ulcer
sharing ipd: Yes
ipd description: The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials/transparency.
As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu
ipd url: https://www.janssen.com/clinical-trials/transparency