A Study of JNJ-66525433 in Healthy Participants and Participants With Ulcerative Colitis

Phase 1

Terminated

• Conditions: Colitis, Ulcerative; Healthy
• Interventions: Drug: Placebo; Drug: JNJ-66525433

• Registration Number: NCT04457960
• Lead Sponsor: Janssen Research & Development, LLC

Brief Summary

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).

Detailed Description

Not available

Study Timeline

• Study Start: 2020-07-01
• Study First Submitted: 2020-07-01
• Study First Submitted QC: 2020-07-01
• Study First Posted: 2020-07-07
• Primary Completion: 2021-10-13
• Study Completion: 2021-10-13
• Status Verified: 2021-12
• Last Update Submitted: 2021-12-29
• Last Update Posted: 2022-01-12

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 82

Inclusion Criteria

For Part 1 and Part 2, healthy volunteers

• Have a body mass index (BMI) between 18 and 30 kilogram per meter square (kg/m^2) (BMI = weight/height), inclusive, and a body weight of no less than 50 kilogram (kg) and maximum weight of 100 kg
• Have normal bowel movements, ranging from 1 to 3 times daily to every other day and have normal consistencies according to the Bristol Stool Scale, ranging from 3 to 5 at admission

For Part 3, participants with ulcerative colitis (UC)

• Have a clinical diagnosis of UC at least 3 months before screening
• Have moderately to severely active UC, defined as a Week 0 mayo score of 6 to 12, inclusive, based on central read of the video endoscopy performed during the screening
• Have a greater than or equal to (>=) 2 endoscopy subscore of the Week 0 mayo score based on central read of the video endoscopy performed during the screening

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Exclusion Criteria

For Part 1 and Part 2, healthy volunteers

• History of liver or renal insufficiency, significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, rheumatologic, psychiatric, or metabolic disturbances
• Known allergies, hypersensitivity, or intolerance to antisense oligonucleotides, JNJ-66525433 or its excipients

For Part 3, participants with UC

• Has UC limited to the rectum only or to <20 centimeter (cm) of the colon evaluated by endoscopy at screening
• Presence of a stoma
• Presence or history of a fistula at any time

COVID-related

• If a participant is excluded due to recent Coronavirus disease (COVID-19) related features, the reason for screen failure should be documented in the case report form under the exclusion criterion of having a condition for which participation would not be in the participant's interest or could confound study assessments
• The field of COVID-related testing (for presence of, and immunity to, the severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] virus) is rapidly evolving. Additional testing may be performed as part of screening and/or during the study if deemed necessary by the investigator and in accordance with current regulations / guidance from authorities / standards of care

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Participants will receive matching placebo in Parts 1, 2 and 3.
JNJ-66525433	JNJ-66525433	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.

Primary Outcome Measures

Name	Time	Method
Part 1, 2 and 3: Number of Participants with Treatment-emergent Adverse Events (TEAEs) as a Measure of Safety and Tolerability	Up to 224 Days	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.
Part 1, 2 and 3: Number of Participants with Vital Sign Abnormalities	Up to 224 Days	Number of participants with vital sign abnormalities (temperature), pulse/heart rate, respiratory rate and blood pressure) will be reported.
Part 1, 2 and 3: Number of Participants with Physical Examination Abnormalities	Up to 224 Days	Number of participants with physical examination abnormalities will be reported.
Part 1, 2 and 3: Number of Participants with Hematology Laboratory Abnormalities	Up to 224 Days	Number of participants with hematology laboratory abnormalities will be reported.
Part 2 and 3: Number of Participants with Abnormalities in High Sensitivity C- Reactive Protein (hs-CRP)	Up to 224 Days	Number of participants with abnormalities in hs-CRP will be reported using a validated, high sensitivity CRP assay.
Part 1, 2 and 3: Number of Participants with Chemistry Laboratory Abnormalities	Up to 224 Days	Number of participants with chemistry laboratory abnormalities will be reported.
Part 1, 2 and 3: Number of Participants with Urinalysis Laboratory Abnormalities	Up to 224 Days	Number of participants with abnormalities in urinalysis will be reported.
Part 2 and 3: Number of Participants with Abnormalities in Fecal Calprotectin	Up to 224 Days	Assays for fecal calprotectin will be performed using a validated method.
Part 2 and 3: Incidence of Enteric Pathogens in Stool Samples	Up to 224 Days	Stool culture and Clostridium difficile toxin assay will be used for enteric pathogen assessment.
Part 1, 2 and 3: Number of Participants with Electrocardiogram (ECG) Abnormalities	Up to 224 Days	Number of participants with ECG abnormalities will be reported.

Secondary Outcome Measures

Name	Time	Method
Part 1: Plasma Concentrations of JNJ-66525433 After Fasted or Fed Dosing	Up to Day 14	Plasma concentrations of JNJ-66525433 after fasted or fed dosing will be reported.
Part 1, 2 and 3: Plasma Concentrations of JNJ-66525433	Up to 224 Days	Plasma concentrations of JNJ-66525433 will be reported.
Part 3: Endoscopic Subscore	Up to Day 84	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).
Part 3: Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score	Days 1, 7, 14, 28, 43, 70 and 84	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.
Part 3: Mayo Score	Up to Day 84	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.
Part 3: Partial Mayo Score	Up to Day 70	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.
Part 2 and 3: Target Engagement of Messenger Ribonucleic Acid (mRNA) Levels	Up to 182 Days	Levels of mRNA knockdown will be reported to assess target engagement in biopsy tissue by dose level over time.
Part 2 and 3: Tissue Biopsy JNJ-66525433 Concentrations	Up to 182 Days	Tissue biopsy concentrations of JNJ-66525433 will be reported.
Faecal Concentrations of JNJ-66525433 After Two Meal Timing Conditions	Predose, up to 120 hours postdose	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).
Plasma Concentrations of JNJ-66525433 After Two Meal Timing Conditions	Up to 22 Days	Plasma concentrations of JNJ-66525433 after two meal timing condition (fed state to modified fasted state) will be reported (if conducted).

Trial Locations

Locations (1)

Charité Research Organisation GmbH; 🇩🇪 Berlin, Germany