Study evaluating the efficacy of icotrokinra in ulcerative colitis
| ISRCTN | ISRCTN13017615 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN13017615 |
| EudraCT/CTIS number | 2025-521381-10 |
| IRAS number | 1012594 |
| ClinicalTrials.gov number | NCT0719674 |
| Secondary identifying numbers | 77242113UCO3001 |
- Submission date
- 12/08/2025
- Registration date
- 06/11/2025
- Last edited
- 06/11/2025
- Recruitment status
- Recruiting
- Overall study status
- Ongoing
- Condition category
- Digestive System
Plain English summary of protocol
Background and study aims
Ulcerative colitis (UC) is a chronic disease of the large intestine in which the lining of the colon becomes inflamed and develops tiny open ulcers. Although there are approved treatment options, many people do not respond or may not be able to tolerate them due to their side effects. Hence, there is still a need for better therapies. The study treatment, icotrokinra (JNJ-77242113), targets interleukin-23 (IL-23R) to prevent IL-23 (a specific type of protein involved in inflammation) from binding to its receptor, which is a protein that binds to a specific molecule. Blocking this protein helps to reduce the inflammation which causes many of the symptoms of UC. In this study, researchers want to evaluate how well icotrokinra works in inducing and maintaining clinical remission (time when the disease is not active and there is a decrease of signs and symptoms) when compared to placebo in adult participants with moderate to severely active UC and how well icotrokinra works in inducing and maintaining clinical remission in adolescent participants (12 years old or older) with moderate to severely active UC.
Who can participate?
Adult and adolescent patients (12 years old or older) with a diagnosis of UC
What does the study involve?
The protocol will be conducted as 3 separate studies below:
1. A 12-week double-blind induction study in adults
2. A 40-week double-blind maintenance study in adults
3. A 52-week open-label induction and maintenance study in adolescents
The overall program is comprised of the following:
1. Screening: Up to 6 weeks
2. Induction: 12 weeks (daily dosing from induction Week 0 (Week I-0) to Week I-12)
3. Maintenance: 40 weeks (daily dosing from maintenance Week 0 (Week M-0) to Week M-40)
4. Long-term extension: Up to 4 years (daily dosing up to Week M-248)
5. Safety follow-up: 4 weeks after the last dose of study treatment
Safety assessments will include adverse events, physical examinations, vital signs, ECG, clinical laboratory testing, suicide assessments, and TB screening. The overall duration of the study is approximately 5 years.
What are the possible benefits and risks of participating?
There is no established benefit to participants of this study. Based on scientific theory, taking icotrokinra may improve UC. However, this cannot be guaranteed because icotrokinra is still under investigation as a treatment, and it is not known whether icotrokinra will work.
Participants may experience some benefit from participation in the study due to regular visits and assessments, and monitoring overall health. Participation may help other people with UC in the future.
Participants may have side effects from the drugs or procedures used in this study that may be mild to severe and even life-threatening, and they can vary from person to person. Potential risks include hypersensitivity reaction, anti-drug antibody (ADA) production, and infection after getting the study drug or placebo. Risk due to study procedure is risks associated with video endoscopy (flexible sigmoidoscopy/full colonoscopy), including bleeding, post-procedure discomfort or intestinal perforation. There are other, less frequent risks. The participant information sheet and informed consent form, which will be signed by every participant agreeing to participate in the study, include a detailed section outlining the known risks of participating in the study.
Not all possible side effects and risks related to icotrokinra are known at this moment. During the study, the sponsor may learn new information about icotrokinra. The study doctor will tell participants as soon as possible about any new information that might make them change their mind about being in the study, such as new risks.
To minimise the risk associated with taking part in the study, participants are frequently reviewed for any side effects and other medical events. Participants are educated to report any such events to their study doctor, who will provide appropriate medical care. Any serious side effects that are reported to the sponsor are thoroughly reviewed by a specialist drug safety team.
There are no costs to participants to be in the study. The sponsor will pay for the study drug and tests that are part of the study. The participant will receive reasonable reimbursement for study-related costs (e.g., travel/parking costs).
Where is the study run from?
Janssen Biologics BV
When is the study starting and how long is it expected to run for?
August 2025 to January 2032
Who is funding the study?
Janssen Research and Development
Who is the main contact?
JanssenUKRegistryQueries@its.jnj.com
Contact information
Principal investigator
Rochdale Old Road
Bury
BL9 7TD
United Kingdom
Principal investigator
50-100 Holmers Farm Way
High Wycombe
HP12 4DP
United Kingdom
| Phone | +44 (0)800 731 8450 / 10494 567 444 |
|---|---|
| JanssenUKRegistryQueries@its.jnj.com |
Study information
| Study design | Placebo-controlled randomized double-blind parallel-group crossover study |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Efficacy, Safety |
| Scientific title | A Phase III randomized, double-blind, placebo-controlled, parallel group, multicenter protocol in adults with an open-label study in adolescents to evaluate the efficacy and safety of induction and maintenance therapy with icotrokinra in participants with moderately to severely active ulcerative colitis |
| Study acronym | ICONIC-UC |
| Study objectives | Primary objectives: 1. To evaluate the efficacy of icotrokinra versus placebo in inducing clinical remission Secondary objectives: 1. To evaluate the efficacy of icotrokinra versus placebo in inducing a range of outcomes 2. To evaluate the safety of icotrokinra versus placebo |
| Ethics approval(s) | Approved 23/10/2025, North West - Greater Manchester Central Research Ethics Committee (3 Piccadilly Place, London Road, Manchester, M1 3BN, UK; +44 (0)2071048057, +44 (0)2071048244, +44 (0)2071048023; gmcentral.rec@hra.nhs.uk), ref: 25/NW/0265 |
| Health condition(s) or problem(s) studied | Ulcerative colitis |
| Intervention | The protocol will be conducted as three separate studies below: 1. A 12-week double-blind induction study in adults 2. A 40-week double-blind maintenance study in adults 3. A 52-week open-label induction and maintenance study in adolescents The overall program is comprised of the following: 1. Screening: Up to 6 weeks 2. Induction: 12 weeks (daily dosing from induction Week 0 (Week I-0) to Week I-12) 3. Maintenance: 40 weeks (daily dosing from maintenance Week 0 (Week M-0) to Week M-40) 4. Long-term Extension: Up to 4 years (daily dosing up to Week M-248) 5. Safety follow-up: 4 weeks after the last dose of study treatment Safety assessments will include adverse events, physical examinations, vital signs, ECG, clinical laboratory testing, suicide assessments, and TB screening. The overall duration of the study is approximately 5 years. Randomization method is via an Interactive Response Technology (IRT) web-based database management program. Double-blind (DB) Induction Study: Experimental: Adult participants will be randomized to receive icotrokinra daily, orally starting at induction Week 0 (Week I-0). At Week I-12, all participants will be evaluated for clinical response and will enter the Maintenance study. Placebo Comparator: Adult participants will be randomized to receive placebo daily, orally starting at Week I-0. At Week I-12, all participants will be evaluated for clinical response and will enter the Maintenance study. DB Maintenance Study: Experimental: Adult participants who are in clinical response to icotrokinra at the end of the Induction study will enter the Maintenance study and be randomized to receive icotrokinra daily, orally starting at maintenance Week 0 (Week M-0) through Week M-40. Participants who are clinical nonresponders to icotrokinra or placebo will also enter the Maintenance study directly and receive icotrokinra daily. After completion of the Maintenance study through Week M-40, eligible participants can participate in a long-term extension (LTE). Placebo Comparator: Adult participants who are in clinical response to icotrokinra at the end of the Induction study will enter the Maintenance study and be randomized to receive placebo daily, orally starting at Week M-0 through Week M-40. Participants who are clinical responders to placebo will also enter the Maintenance study directly and continue to receive placebo daily. After completion of the Maintenance study through Week M-40, eligible participants can participate in a LTE. Open-label (OL) Induction Phase: Experimental: Adolescent participants will enter the Induction phase and receive icotrokinra daily, orally. At Week I-12 all participants will be evaluated for clinical response and will enter the Maintenance phase. OL Maintenance Phase: Experimental: Adolescent participants who are in clinical response to icotrokinra will enter the Maintenance phase at Week M-0 and continue to receive icotrokinra daily, orally up to Week M-40. Participants who are nonresponders to icotrokinra will also enter the Maintenance phase to receive icotrokinra daily. After completion of the Maintenance phase through Week M-40, eligible participants can participate in a LTE. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | Pharmacokinetic, Pharmacodynamic, Dose response, Pharmacogenomic, Therapy, Biomarkers |
| Phase | Phase III |
| Drug / device / biological / vaccine name(s) | Icotrokinra [JNJ-77242113-AAC] |
| Primary outcome measure | 1. Induction study (adult): Clinical remission, measured using the modified MAYO score with a stool frequency subscore of 0 or 1, a rectal bleeding subscore of 0, and an endoscopy subscore of 0 or 1, at Week 12 (I-12) 2. Maintenance study (adult): Clinical remission, measured using the modified MAYO score with a stool frequency subscore of 0 or 1, a rectal bleeding subscore of 0, and an endoscopy subscore of 0 or 1, at Week 52 (M-40) 3. Adolescent study: Clinical remission, measured using the modified MAYO score with a stool frequency subscore of 0 or 1, a rectal bleeding subscore of 0, and an endoscopy subscore of 0 or 1, at Week 52 (M-40) |
| Secondary outcome measures | Induction: 1. Clinical response at Week 12 (I-12), measured using the modified MAYO score defined as a decrease from baseline in the modified Mayo score by ≥30% and ≥2 points, with either a ≥1-point decrease from baseline in the rectal bleeding subscore or a rectal bleeding subscore of 0 or 1. 2. Endoscopic improvement at Week 12 (I-12) measured by a Mayo endoscopy subscore of 0 or 1. 3. Symptomatic remission at Week 12 (I-12) measured by a Mayo stool frequency subscore of 0 or 1 and a rectal bleeding subscore of 0. 4. Inflammatory Bowel Disease Questionnaire (IBDQ) remission at Week 12 (I-12) measured as an IBDQ total score ≥170. 5. Histologic-endoscopic mucosal improvement at Week 12 (I-12) measured as a combination of histologic improvement (neutrophil infiltration in <5% of crypts, no crypt destruction, and no erosions, ulcerations, or granulation tissue according to the Geboes grading system) and endoscopic improvement: Mayo endoscopy subscore of 0 or 1. 6. Fatigue response at Week 12 (I-12) measured as A ≥7-point reduction in the PROMIS-Fatigue SF-7a total score from baseline. 7. Symptomatic remission at Week 4 (I-4) measured by a Mayo stool frequency subscore of 0 or 1 and a rectal bleeding subscore of 0. 8. Endoscopic remission at Week 12 (I-12) measured as a Mayo endoscopy subscore of 0. 9. No bowel urgency at Week 12 (I-12) measured as a rounded weekly average of daily scores of ‘0’ for question 7 of the UC-PRO/SS. 10. No abdominal pain at Week 12 (I-12) measured as a rounded weekly average of daily scores of ‘0’ for question 8 of the UC-PRO/SS. 11. No bowel incontinence at Week 12 (I-12) measured as a rounded weekly average of daily scores of ‘0’ for question 5 of the UC-PRO/SS. Maintenance secondary outcome measures are assessed at Week 52 (M-40): 1. Endoscopic improvement measured by a Mayo endoscopy subscore of 0 or 1. 2. Symptomatic remission measured by a Mayo stool frequency subscore of 0 or 1 and a rectal bleeding subscore of 0. 3. 90-day corticosteroid-free clinical remission measured as clinical remission at the visit and not receiving corticosteroids for 90 days prior to the visit. 4. Histologic-endoscopic mucosal improvement measured as a combination of histologic improvement (neutrophil infiltration in < 5% of crypts, no crypt destruction, and no erosions, ulcerations, or granulation tissue according to the Geboes grading system) and endoscopic improvement: Mayo endoscopy subscore of 0 or 1. 5. IBDQ remission measured as an IBDQ total score ≥170 6. Endoscopic remission measured as a Mayo endoscopy subscore of 0 7. Clinical remission among the participants who had achieved clinical remission at maintenance baseline (i.e., maintenance of clinical remission) measured as a Mayo stool frequency subscore of 0 or 1, a rectal bleeding subscore of 0, and an endoscopy subscore of 0 or 1 8. Histologic-endoscopic mucosal remission measured as achieving a combination of histologic remission (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), and endoscopic remission (Mayo endoscopy subscore of 0) 9. Fatigue response measured as a ≥7-point reduction in the PROMIS-Fatigue SF-7a total score from baseline 10. Disease clearance measured as a composite of symptomatic remission and histologic-endoscopic mucosal remission 11. No bowel urgency measured as a rounded weekly average of daily scores of ‘0’ for question 7 of the UC-PRO/SS 12. No abdominal pain measured as a rounded weekly average of daily scores of ‘0’ for question 8 of the UC-PRO/SS 13. No bowel incontinence measured as a rounded weekly average of daily scores of ‘0’ for question 5 of the UC-PRO/SS |
| Overall study start date | 08/08/2025 |
| Completion date | 13/01/2032 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Mixed |
| Lower age limit | 12 Years |
| Sex | All |
| Target number of participants | 882 |
| Key inclusion criteria | 1. Adult participants: ≥18 years of age (and at least the legal age of consent in the jurisdiction in which the study is taking place). Adolescent participants: ≥12 to <18 years of age, at the time of signing the informed assent/consent. 2. Diagnosis of UC established at least 12 weeks before screening, including both endoscopic evidence and a histopathology report consistent with a diagnosis of UC. 3. Moderately to severely active UC, defined as baseline (Week I-0) modified Mayo score of 5 to 9, inclusive, using the endoscopy subscore obtained during the central review of the screening video endoscopy. 4. An endoscopy subscore ≥2 as obtained during central review of the screening video endoscopy. 5. A participant who has had extensive UC for ≥8 years, or disease limited to the left side of the colon for ≥ 10 years before the first dose of study intervention, must undergo a complete colonoscopy to assess for the presence of dysplasia within 1 year before the first dose of study intervention. Completion of the colonoscopy with dysplasia assessment is allowed during the screening period prior to the first dose of study intervention. |
| Key exclusion criteria | 1. Participants with current known complications of UC such as fulminant colitis, toxic megacolon, or any other manifestation that might require colonic surgery while enrolled in the study. 2. Presence of a stoma. 3. Presence or history of fistula. 4. Colonic resection within 24 weeks before baseline or any other intra abdominal or other major surgery performed within 12 weeks before baseline. 5. History or screening colonoscopy finding of high- or low-grade colonic mucosal dysplasia in an area of known colitis (active or historic). |
| Date of first enrolment | 01/10/2025 |
| Date of final enrolment | 08/12/2026 |
Locations
Countries of recruitment
- Argentina
- Australia
- Belgium
- Brazil
- Canada
- China
- England
- France
- Germany
- Greece
- Hungary
- India
- Israel
- Italy
- Japan
- Malaysia
- Netherlands
- Poland
- Portugal
- Romania
- Scotland
- Spain
- Sweden
- Switzerland
- Taiwan
- United Kingdom
Study participating centres
Bury
BL9 7TD
United Kingdom
London
SW17 0QT
United Kingdom
Cambridge
CB2 0QQ
United Kingdom
London
SE5 9RS
United Kingdom
Prescot
L35 5DR
United Kingdom
Leytonstone
London
E11 1NR
United Kingdom
Stepping Hill Hospital
Poplar Grove
Stockport
SK2 7JE
United Kingdom
Sheffield
S10 2TH
United Kingdom
Edinburgh
Lothian
EH16 4TJ
United Kingdom
Sponsor information
Industry
Janssen Biologics BV - Clinical Registry Group - Archimedesweg 29
Leiden
2333 CM
Netherlands
| ClinicalTrialsEU@its.jnj.com |
Funders
Funder type
Industry
Private sector organisation / For-profit companies (industry)
- Alternative name(s)
- Janssen R&D, Janssen Research & Development, Janssen Research & Development, LLC, Janssen Research & Development LLC, Janssen Pharmaceutical Companies of Johnson & Johnson, Research & Development at Janssen, JRD, J&J PRD
- Location
- United States of America
Results and Publications
| Intention to publish date | 13/01/2033 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| Publication and dissemination plan | 1. Peer reviewed scientific journals 2. Internal report 3. Conference presentation 4. Submission to regulatory authorities 5. Results of the study will be available to the wider scientific community via publication in scientific journals and presentation at scientific meetings 6. Study results will be available to participants via provision of a Plain Language Summary at the end of the study, and in addition, results will be published in the EudraCT database and in accordance with HRA requirements (lay summary of results in the final HRA Report) |
| IPD sharing plan | The data sharing plans for the current study are unknown and will be made available at a later date |
Editorial Notes
24/10/2025: ISRCTN received notification of combined HRA/MHRA approval for this trial on 24/10/2025.
12/08/2025: Study's existence confirmed by Health Research Authority (HRA) (UK)
