Clinical trial NCT04457960: A Study of JNJ-66525433 in Healthy Participants and Participants With Ulcerative Colitis
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Healthy
Colitis, Ulcerative
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2020-07-07
Enrollment: 82
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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).


Eligibility criteria: 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

Primary outcomes:
measure: Part 1, 2 and 3: Number of Participants with Treatment-emergent Adverse Events (TEAEs) as a Measure of Safety and Tolerability
timeFrame: Up to 224 Days
measure: Part 1, 2 and 3: Number of Participants with Vital Sign Abnormalities
timeFrame: Up to 224 Days
measure: Part 1, 2 and 3: Number of Participants with Physical Examination Abnormalities
timeFrame: Up to 224 Days
measure: Part 1, 2 and 3: Number of Participants with Hematology Laboratory Abnormalities
timeFrame: Up to 224 Days
measure: Part 1, 2 and 3: Number of Participants with Chemistry Laboratory Abnormalities
timeFrame: Up to 224 Days
measure: Part 1, 2 and 3: Number of Participants with Urinalysis Laboratory Abnormalities
timeFrame: Up to 224 Days
measure: Part 2 and 3: Number of Participants with Abnormalities in High Sensitivity C- Reactive Protein (hs-CRP)
timeFrame: Up to 224 Days
measure: Part 2 and 3: Number of Participants with Abnormalities in Fecal Calprotectin
timeFrame: Up to 224 Days
measure: Part 2 and 3: Incidence of Enteric Pathogens in Stool Samples
timeFrame: Up to 224 Days
measure: Part 1, 2 and 3: Number of Participants with Electrocardiogram (ECG) Abnormalities
timeFrame: Up to 224 Days
Secondary outcomes:
measure: Part 1, 2 and 3: Plasma Concentrations of JNJ-66525433
timeFrame: Up to 224 Days
measure: Part 1: Plasma Concentrations of JNJ-66525433 After Fasted or Fed Dosing
timeFrame: Up to Day 14
measure: Part 3: Mayo Score
timeFrame: Up to Day 84
measure: Part 3: Partial Mayo Score
timeFrame: Up to Day 70
measure: Part 3: Endoscopic Subscore
timeFrame: Up to Day 84
measure: Part 3: Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score
timeFrame: Days 1, 7, 14, 28, 43, 70 and 84
measure: Part 2 and 3: Target Engagement of Messenger Ribonucleic Acid (mRNA) Levels
timeFrame: Up to 182 Days
measure: Part 2 and 3: Tissue Biopsy JNJ-66525433 Concentrations
timeFrame: Up to 182 Days
measure: Plasma Concentrations of JNJ-66525433 After Two Meal Timing Conditions
timeFrame: Up to 22 Days
measure: Faecal Concentrations of JNJ-66525433 After Two Meal Timing Conditions
timeFrame: Predose, up to 120 hours postdose
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Charite Research Organisation GmbH
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: