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

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

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).

Study Overview

• Status: Terminated
• Conditions: Healthy; Colitis, Ulcerative
• Intervention / Treatment: Drug: JNJ-66525433; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 82
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 10117
    • Charite Research Organisation GmbH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 58 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: JNJ-66525433; Participants will receive JNJ-66525433 oral capsules.
Placebo Comparator: Placebo; Participants will receive matching placebo in Parts 1, 2 and 3.	Drug: Placebo; Participants will receive matching placebo oral capsules.

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2020
• Primary Completion (Actual): October 13, 2021
• Study Completion (Actual): October 13, 2021

Study Registration Dates

• First Submitted: July 1, 2020
• First Submitted That Met QC Criteria: July 1, 2020
• First Posted (Actual): July 7, 2020

Study Record Updates

• Last Update Posted (Actual): January 12, 2022
• Last Update Submitted That Met QC Criteria: December 29, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Gastroenteritis; Colonic Diseases; Intestinal Diseases; Inflammatory Bowel Diseases; Ulcer; Colitis; Colitis, Ulcerative
• Other Study ID Numbers: CR108764; 2018-003743-29 (EudraCT Number); 66525433IBD1001 (Other Identifier: Janssen Research & Development, LLC)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes

IPD Plan 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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes