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

Primary Purpose

Healthy, Colitis, Ulcerative

Status

Terminated

Phase

Phase 1

Locations

Germany

Study Type

Interventional

Intervention

JNJ-66525433

Placebo

About this trial

This is an interventional treatment trial for Healthy

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

Charité Research Organisation GmbH

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

JNJ-66525433

Placebo

Arm 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.

Participants will receive matching placebo in Parts 1, 2 and 3.

Outcomes

Primary Outcome Measures

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.

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.

Part 1, 2 and 3: Number of Participants with Physical Examination Abnormalities

Number of participants with physical examination abnormalities will be reported.

Part 1, 2 and 3: Number of Participants with Hematology Laboratory Abnormalities

Number of participants with hematology laboratory abnormalities will be reported.

Part 1, 2 and 3: Number of Participants with Chemistry Laboratory Abnormalities

Number of participants with chemistry laboratory abnormalities will be reported.

Part 1, 2 and 3: Number of Participants with Urinalysis Laboratory Abnormalities

Number of participants with abnormalities in urinalysis will be reported.

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.

Part 2 and 3: Number of Participants with Abnormalities in Fecal Calprotectin

Assays for fecal calprotectin will be performed using a validated method.

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.

Part 1, 2 and 3: Number of Participants with Electrocardiogram (ECG) Abnormalities

Number of participants with ECG abnormalities will be reported.

Secondary Outcome Measures

Part 1, 2 and 3: Plasma Concentrations of JNJ-66525433

Plasma concentrations of JNJ-66525433 will be reported.

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.

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.

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.

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).

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.

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.

Part 2 and 3: Tissue Biopsy JNJ-66525433 Concentrations

Tissue biopsy concentrations of JNJ-66525433 will be reported.

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).

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).

Full Information

NCT ID

NCT04457960

First Posted

July 1, 2020

Last Updated

December 29, 2021

Sponsor

Janssen Research & Development, LLC

1. Study Identification

Unique Protocol Identification Number

NCT04457960

Brief Title

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

2. Study Status

Record Verification Date

December 2021

Overall Recruitment Status

Terminated

Why Stopped

Sponsor Decision.

Study Start Date

July 1, 2020 (Actual)

Primary Completion Date

October 13, 2021 (Actual)

Study Completion Date

October 13, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Janssen Research & Development, LLC

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Yes

Data Monitoring Committee

Yes

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Healthy, Colitis, Ulcerative

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Sequential Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

82 (Actual)

8. Arms, Groups, and Interventions

Arm Title

JNJ-66525433

Arm Type

Experimental

Arm 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 Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Participants will receive matching placebo in Parts 1, 2 and 3.

Intervention Type

Drug

Intervention Name(s)

JNJ-66525433

Intervention Description

Participants will receive JNJ-66525433 oral capsules.

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Participants will receive matching placebo oral capsules.

Primary Outcome Measure Information:

Title

Part 1, 2 and 3: Number of Participants with Treatment-emergent Adverse Events (TEAEs) as a Measure of Safety and Tolerability

Description

Time Frame

Up to 224 Days

Title

Part 1, 2 and 3: Number of Participants with Vital Sign Abnormalities

Description

Number of participants with vital sign abnormalities (temperature), pulse/heart rate, respiratory rate and blood pressure) will be reported.

Time Frame

Up to 224 Days

Title

Part 1, 2 and 3: Number of Participants with Physical Examination Abnormalities

Description

Number of participants with physical examination abnormalities will be reported.

Time Frame

Up to 224 Days

Title

Part 1, 2 and 3: Number of Participants with Hematology Laboratory Abnormalities

Description

Number of participants with hematology laboratory abnormalities will be reported.

Time Frame

Up to 224 Days

Title

Part 1, 2 and 3: Number of Participants with Chemistry Laboratory Abnormalities

Description

Number of participants with chemistry laboratory abnormalities will be reported.

Time Frame

Up to 224 Days

Title

Part 1, 2 and 3: Number of Participants with Urinalysis Laboratory Abnormalities

Description

Number of participants with abnormalities in urinalysis will be reported.

Time Frame

Up to 224 Days

Title

Part 2 and 3: Number of Participants with Abnormalities in High Sensitivity C- Reactive Protein (hs-CRP)

Description

Number of participants with abnormalities in hs-CRP will be reported using a validated, high sensitivity CRP assay.

Time Frame

Up to 224 Days

Title

Part 2 and 3: Number of Participants with Abnormalities in Fecal Calprotectin

Description

Assays for fecal calprotectin will be performed using a validated method.

Time Frame

Up to 224 Days

Title

Part 2 and 3: Incidence of Enteric Pathogens in Stool Samples

Description

Stool culture and Clostridium difficile toxin assay will be used for enteric pathogen assessment.

Time Frame

Up to 224 Days

Title

Part 1, 2 and 3: Number of Participants with Electrocardiogram (ECG) Abnormalities

Description

Number of participants with ECG abnormalities will be reported.

Time Frame

Up to 224 Days

Secondary Outcome Measure Information:

Title

Part 1, 2 and 3: Plasma Concentrations of JNJ-66525433

Description

Plasma concentrations of JNJ-66525433 will be reported.

Time Frame

Up to 224 Days

Title

Part 1: Plasma Concentrations of JNJ-66525433 After Fasted or Fed Dosing

Description

Plasma concentrations of JNJ-66525433 after fasted or fed dosing will be reported.

Time Frame

Up to Day 14

Title

Part 3: Mayo Score

Description

Time Frame

Up to Day 84

Title

Part 3: Partial Mayo Score

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.

Time Frame

Up to Day 70

Title

Part 3: Endoscopic Subscore

Description

Time Frame

Up to Day 84

Title

Part 3: Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score

Description

Time Frame

Days 1, 7, 14, 28, 43, 70 and 84

Title

Part 2 and 3: Target Engagement of Messenger Ribonucleic Acid (mRNA) Levels

Description

Levels of mRNA knockdown will be reported to assess target engagement in biopsy tissue by dose level over time.

Time Frame

Up to 182 Days

Title

Part 2 and 3: Tissue Biopsy JNJ-66525433 Concentrations

Description

Tissue biopsy concentrations of JNJ-66525433 will be reported.

Time Frame

Up to 182 Days

Title

Plasma Concentrations of JNJ-66525433 After Two Meal Timing Conditions

Description

Plasma concentrations of JNJ-66525433 after two meal timing condition (fed state to modified fasted state) will be reported (if conducted).

Time Frame

Up to 22 Days

Title

Faecal Concentrations of JNJ-66525433 After Two Meal Timing Conditions

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).

Time Frame

Predose, up to 120 hours postdose

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

60 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Janssen Research & Development, LLC Clinical Trial

Organizational Affiliation

Janssen Research & Development, LLC

Official's Role

Study Director

Facility Information:

Facility Name

Charité Research Organisation GmbH

City

Berlin

ZIP/Postal Code

10117

Country

Germany

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing 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

IPD Sharing URL

https://www.janssen.com/clinical-trials/transparency

Learn more about this trial

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

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