A Study of JNJ-78934804 in Participants With Moderately to Severely Active Ulcerative Colitis (DUET ENCORE-UC)

A Phase 3 Randomized, Double-blind, and Active Controlled, Multi-center Study to Evaluate the Efficacy and Safety of JNJ-78934804 in Participants With Moderately to Severely Active Ulcerative Colitis

The purpose of this study is to assess how well JNJ-78934804 works (efficacy) and how safe it is (safety) as compared to guselkumab at Week 48 in participants with moderately to severely active ulcerative colitis (UC, a chronic disease of the large intestine in which the lining of the colon becomes inflamed and develops ulcers).

Study Overview

• Status: Not yet recruiting
• Conditions: Colitis, Ulcerative
• Intervention / Treatment: Drug: Guselkumab; Drug: JNJ-78934804

• Study Type: Interventional
• Enrollment (Estimated): 644
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Study Contact; Phone Number: 844-434-4210; Email: Participate-In-This-Study1@its.jnj.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion criteria:

• Diagnosis of ulcerative colitis (UC) established at least 12 weeks before screening including both endoscopic evidence and a histopathology report consistent with a diagnosis of UC.
• Moderately to severely active UC defined as baseline (Week 0) modified Mayo score of 5 to 9, inclusive, using the Mayo endoscopy subscore obtained during central review of the screening video endoscopy
• An endoscopy subscore >=2 as obtained during central review of the screening video endoscopy
• Have had an inadequate initial response, loss of response, or intolerance to previous approved systemic therapies

Exclusion criteria:

• Isolated proctitis (UC limited to the rectum only or to less than [<] 20 centimeter [cm] from the anal verge) as determined during central review of the screening video endoscopy OR Has a diagnosis of isolated proctitis
• Diagnosis of indeterminate colitis, microscopic colitis, ischemic colitis, Crohn's colitis or any findings suggestive of CD
• Has a history of or ongoing chronic or recurrent infectious disease
• Has previously demonstrated inadequate initial response, loss of response, allergy, hypersensitivity or intolerance to guselkumab or to golimumab
• Is a participant who is pregnant, breastfeeding, or planning to become pregnant, or plans to father a child, while enrolled in this study or within 6 months after the last dose of study intervention

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: JNJ-78934804; Participants will receive JNJ-78934804 induction dose at Weeks 0, 4, and 8 followed by JNJ-78934804 maintenance dose, once every 4 weeks (q4w) starting at Week 12. All participants who meet the rescue criteria will receive JNJ-78934804 induction dose at Weeks 16, 20, and 24 followed by JNJ-78934804 maintenance dose q4w starting at Week 28. Participants who complete double-blind (DB) treatment phase (Week 48) and benefit from continued study intervention in the opinion of the investigator will have the opportunity to enter the long-term extension (LTE) phase.	Drug: JNJ-78934804; JNJ-78934804 will be administered subcutaneously.; Other Names: JNJ-4804
Active Comparator: Guselkumab; Participants with moderately to severely active UC will receive guselkumab induction dose at Weeks 0, 4, and 8 followed by guselkumab maintenance dose q4w starting at Week 12. All participants who meet the rescue criteria will receive JNJ-78934804 induction dose at Weeks 16, 20, and 24 followed by JNJ-78934804 maintenance dose q4w starting at Week 28. Participants who complete DB treatment phase (Week 48) and benefit from continued study intervention in the opinion of the investigator will have the opportunity to enter the LTE phase.	Drug: Guselkumab; Guselkumab will be administered subcutaneously.; Other Names: TREMFYA; Drug: JNJ-78934804; JNJ-78934804 will be administered subcutaneously.; Other Names: JNJ-4804

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants in Clinical Remission at Week 48	Clinical remission is defined as an stool frequency (SF) subscore of 0 or 1, rectal bleeding (RB) subscore of 0, and an endoscopy subscore of 0 or 1.	At Week 48

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants with Endoscopic Improvement at Week 48	Endoscopic improvement is defined as an endoscopy subscore of 0 or 1.	At Week 48
Percentage of Participants with Corticosteroid-free (90 day) Clinical Remission at Week 48	Corticosteroid-free (90 day) clinical remission is defined as clinical remission at the visit and not receiving corticosteroids for 90 days prior to the visit.	At Week 48
Percentage of Participants Achieving a Combination of Histologic Remission and Endoscopic Improvement at Week 48	Endoscopic improvement is defined as an endoscopy subscore of 0 or 1. Histologic remission is defined as an absence of neutrophils from the mucosa (both lamina propria and epithelium), no crypt destruction, and no erosions, ulcerations or granulation tissue according to the Geboes grading system.	At Week 48
Percentage of Participants with Fatigue Response (PROMIS Fatigue Short Form 7a) at Week 48	Fatigue response is defined as a greater than or equal to (>=) 7- point reduction in the patient-reported outcomes measurement information system (PROMIS) fatigue short form 7a total score from baseline. The PROMIS fatigue SF-7a contains 7 items evaluating fatigue-related symptoms (that is, tiredness, exhaustion, mental tiredness, and lack of energy) and associated impacts on daily activities (that is, activity limitations related to work, self-care, and exercise).	At Week 48
Percentage of Participants with Sustained Mayo SF Less Than or Equal to (<=) 1 and RB=0	Percentage of participants with a SF subscore of 0 or 1 and RB subscore of 0 at three assessment time points of Week 12, Week 24, and Week 48 will be reported.	At Weeks 12, 24, and 48
Percentage of Participants in Abdominal Pain Remission at Week 48	Percentage of participants in abdominal pain remission at week 48 will be reported.	At Week 48
Percentage of Participants with Inflammatory Bowel Disease Questionnaire (IBDQ) Response at Week 48	IBDQ response is defined as improvement from baseline in the total IBDQ score of >= 16 points. The IBDQ is a 32-item, self-reported questionnaire for participants with IBD that will be used to evaluate the disease-specific health-related quality of life (HRQoL) 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).	At Week 48
Percentage of Participants with PROMIS-29 Mental Component Summary (MCS) Response at Week 48	PROMIS 29 MCS response is defined as a >= 7-point improvement from baseline in PROMIS 29 MCS response at Week 48. The PROMIS-29 is a collection of short forms containing 4 items for each of 7 domains (depression, anxiety, physical function, pain interference, fatigue, sleep disturbance, and ability to participate in social roles and activities). The PROMIS-29 MCS will be assessed, which is primarily informed by domains of emotional distress (depression/anxiety) and fatigue as well as sleep disturbance where higher MCS scores reflect better mental health.	At Week 48
Percentage of Participants in Clinical Remission at Week 12	Clinical remission is defined as an SF subscore of 0 or 1, RB subscore of 0, and an endoscopy subscore of 0 or 1.	At Week 12
Percentage of Participants with Endoscopic Improvement at Week 12	Endoscopic improvement is defined as an endoscopy subscore of 0 or 1.	At Week 12
Percentage of Participants with Mayo SF/RB Response at Week 2	Mayo SF/RB response is defined as a decrease from baseline in the sum of the SF and the RB subscores by >=30 percent (%) and >= 1 point, with either a >= 1 point decrease from baseline in the RB subscore or an RB subscore of 0 or 1.	At Week 2
Percentage of Participants with Adverse Events (AE) and Serious AEs (SAEs)	An AE is any untoward medical occurrence in a clinical study participant administered a pharmaceutical (investigational or non investigational) product. An AE does not necessarily have a causal relationship with the intervention. An SAE is any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/ incapacity, is a congenital anomaly/birth defect, is a suspected transmission of any infectious agent via a medicinal product, and is medically important.	Up to approximately 3 years

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC
• Investigators: Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC

Study record dates

Study Major Dates

• Study Start (Estimated): May 29, 2026
• Primary Completion (Estimated): August 11, 2028
• Study Completion (Estimated): October 30, 2030

Study Registration Dates

• First Submitted: May 5, 2026
• First Submitted That Met QC Criteria: May 5, 2026
• First Posted (Actual): May 11, 2026

Study Record Updates

• Last Update Posted (Actual): May 11, 2026
• Last Update Submitted That Met QC Criteria: May 5, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Intestinal Diseases; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Gastroenteritis; Inflammatory Bowel Diseases; Colitis; Colitis, Ulcerative; guselkumab
• Other Study ID Numbers: 78934804UCO3001; 2026-525923-26-00 (Registry Identifier: EUCT number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The data sharing policy of Johnson & Johnson Innovative Medicine is available at www.innovativemedicine.jnj.com/our-innovation/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