A Study of Icotrokinra in participants with moderately to severely active Crohn's disease
| ISRCTN | ISRCTN15911581 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN15911581 |
| Clinical Trials Information System (CTIS) | 2025-521382-27 |
| Integrated Research Application System (IRAS) | 1012360 |
| Central Portfolio Management System (CPMS) | 67835 |
| Protocol serial number | 77242113CRD3001 |
| Sponsor | Janssen-Cilag International N.V. |
| Funder | Janssen Research and Development |
- Submission date
- 07/08/2025
- Registration date
- 13/10/2025
- Last edited
- 13/11/2025
- Recruitment status
- Recruiting
- Overall study status
- Ongoing
- Condition category
- Digestive System
Plain English summary of protocol
Background and study aims
Crohn’s Disease (CD) is a disease of the digestive system that causes inflammation and ulcers in the intestine (gut).
Although there are approved treatment options, participants either do not respond or may not tolerate them due to side effects. Hence, there is a need for better treatment options.
Icotrokinra (JNJ-77242113) targets interleukin-23 (IL-23R) to prevent IL-23* from binding to its receptor**. Blocking this protein helps to reduce inflammation.
*Protein involved in inflammation
**Protein that binds to a specific molecule
Researchers want to assess how well icotrokinra works when compared to placebo (treatment with no medical effect).
Who can participate?
Participants aged 18 years or older with moderate to severely active CD.
What does the study involve?
Overall study consists of 3 separate studies as below:
o Phase 2b Induction Dose-ranging Study (Induction Study 1)
o Phase 3 Induction Study (Induction Study 2)
o Phase 3 Maintenance Study
Study consists of:
o Screening period (up to 6 weeks)
o Induction Study periods: Daily dosing from Week I-0 to Week I-12
o Induction Study 1:
o Icotrokinra Dose 1
o Icotrokinra Dose 2
o Placebo
o Induction Study 2:
o Icotrokinra: As per dose from induction study 1
o Placebo
o Maintenance Study: Daily dosing from Week M-0 to Week M-40. Responder participants from induction study 1 and 2 will receive either:
o Icotrokinra Dose 1
o Icotrokinra Dose 2
o Placebo
- Responder participants who show loss of response during the maintenance study will be eligible for dose adjustment to icotrokinra
- Non-responder participants will receive icotrokinra dose 2, and will be reassessed at week M-12 and continue in the study if in response.
o Long term extension study period: Daily dosing up to Week M-248.
o Safety follow-up period (up to 4 weeks after last dose of study treatment)
Safety assessments include adverse events, physical examinations, vital signs, electrocardiogram, clinical laboratory tests, suicide assessments, and tuberculosis screening. The duration of the study will be 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 CD. However, this cannot be guaranteed because icotrokinra is still under investigation as a treatment and it is not known whether icotrokinra will work.
In addition, if participants are put into the placebo treatment group they may not receive icotrokinra and may only receive placebo during this study unless specified.
Participants may experience some benefit from participation in the study that is not due to receiving study drug, but due to regular visits and assessments monitoring overall health. Participation may help other people with CD 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 (exaggerated immune response) reactions, anti-drug antibody (ADA) antibodies developed against drugs reducing their therapeutic efficacy) production and infections after getting the study drug or placebo.
Risks due to study procedure include video ileocolonoscopy (complete colonoscopy; procedure for examining parts of intestine and colon using tube called colonoscope), including bleeding, post procedure discomfort or intestinal perforation (formation of holes in
intestine) after the procedure. 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, includes a detailed section outlining the known risks to 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-Cilag International N.V. (Netherlands)
When is the study starting and how long is it expected to run for?
August 2025 to March 2033
Who is funding the study?
Janssen-Cilag International N.V. (Netherlands)
Who is the main contact?
medinfo@its.jnj.com
Contact information
Public, Scientific
50-100 Holmers Farm Way
High Wycombe
HP124DP
United Kingdom
| JanssenUKRegistryQueries@its.jnj.com |
Principal investigator
Glasgow Royal Infirmary
Glasgow
G4 0SF
United Kingdom
Study information
| Primary study design | Interventional |
|---|---|
| Study design | Interventional double blind randomized cross over group placebo controlled trial |
| Secondary study design | Randomised cross over trial |
| Scientific title | A phase 2b/3 randomized, double-blind, placebo-controlled, parallel group, multicenter protocol to evaluate the efficacy and safety of Icotrokinra in participants with moderately to severely active Crohn's Disease |
| Study acronym | ICONIC-CD |
| Study objectives | Primary objectives: Induction 1 To evaluate the efficacy of icotrokinra versus placebo in inducing clinical response Induction 2 To evaluate the efficacy of icotrokinra versus placebo in induction Maintenance To evaluate the efficacy of icotrokinra versus placebo in maintenance Secondary objectives: Induction 1 To evaluate the efficacy of icotrokinra versus placebo in inducing a range of outcomes in induction To evaluate the dose-response of icotrokinra to inform dose selection for the Phase 3 induction study of this protocol To evaluate the safety of icotrokinra versus placebo Induction 2 To evaluate the efficacy of icotrokinra versus placebo over a range of outcomes in induction To evaluate the safety of icotrokinra versus placebo Maintenance To evaluate the safety of icotrokinra versus placebo To evaluate the efficacy of icotrokinra versus placebo across a range of outcomes |
| Ethics approval(s) |
Approved 11/10/2025, Wales REC 1 (Health and Care Research Wales, Castlebridge 4, Cardiff, CF11 9AB, United Kingdom; +44 (0)2920 230 457; Wales.REC1@wales.nhs.uk), ref: 25/WA/0249 |
| Health condition(s) or problem(s) studied | Moderate to Severe Crohn's disease, Plaque psoriasis |
| Intervention | In Induction Study 1, participants are assigned to one of three arms. In the first experimental arm, participants will receive Icotrokinra Dose 1 up to Week 12. Subsequent treatment will be determined by the participant's response status at Week 12. The drug, Icotrokinra (also known as JNJ-77242113), will be administered orally, daily. In the second experimental arm of Induction Study 1, participants will receive Icotrokinra Dose 2 up to Week 12. As with Dose 1, subsequent treatment will be determined by the participant's response status at Week 12. Icotrokinra will be administered orally, daily, and is also referred to as JNJ-77242113. The third arm of Induction Study 1 is a placebo comparator. Participants will receive a matching placebo up to Week 12. Subsequent treatment will be determined by the participant's response status at Week 12. The placebo will be administered orally, daily. In Induction Study 2, participants will receive Icotrokinra at the dose regimen determined in Induction Study 1, up to Week 12. Subsequent study treatment will be determined by the participant's response status at Week 12. Icotrokinra, also known as JNJ-77242113, will be administered orally, daily. The placebo comparator arm of Induction Study 2 involves participants receiving a matching placebo for up to Week 12. Subsequent study treatment will be determined by the participant's response status at Week 12. The placebo will be administered orally, daily. In the Maintenance Study, participants who were receiving Icotrokinra in either Induction Study 1 or 2 and were in response at Week 12 will be randomized to receive Icotrokinra Maintenance Dose 1. Participants receiving Dose 1 and meeting criteria for loss of response during the Maintenance Study will be eligible for a single blinded dose adjustment to Icotrokinra Dose 2. After completion of the Maintenance Study through Week 40, eligible participants can participate in long-term extension (LTE). Icotrokinra will be administered orally, daily. Another arm of the Maintenance Study involves participants who were receiving Icotrokinra in either induction study and were in response at Week 12 being randomized to receive Icotrokinra Maintenance Dose 2. Participants who were non-responders at Week 12 of the induction studies will also receive Icotrokinra Maintenance Dose 2 but will not be randomized. After completion of the Maintenance Study through Week 40, eligible participants can participate in LTE. Icotrokinra will be administered orally, daily. The placebo comparator arm of the Maintenance Study includes participants who were receiving Icotrokinra in either induction study and were in response at Week 12 being randomized to receive placebo. Participants receiving placebo in induction studies and in response at Week 12 will continue to receive placebo during maintenance on a non-randomized basis. Placebo non-responders from the induction study will receive Icotrokinra Maintenance Dose 2 on a non-randomized basis and will be assessed for response at Week 12. Participants receiving placebo and meeting criteria for loss of response during the Maintenance Study will be eligible for a single blinded dose adjustment to Icotrokinra Dose 2. After completion of the Maintenance Study through Week 40, eligible participants can participate in LTE. Icotrokinra (JNJ-77242113) and matching placebo will be administered orally, daily. |
| Intervention type | Drug |
| Phase | Phase III |
| Drug / device / biological / vaccine name(s) | JNJ-77242113 |
| Primary outcome measure(s) |
1. Clinical response is measured using the Mayo Clinic Score at baseline and Week 12 |
| Key secondary outcome measure(s) |
1. Clinical remission is measured using the Mayo Clinic Score at baseline, Week I-4, and Week I-12 |
| Completion date | 31/03/2033 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Mixed |
| Lower age limit | 18 Years |
| Upper age limit | 99 Years |
| Sex | All |
| Target sample size at registration | 1092 |
| Key inclusion criteria | 1. Diagnosis of CD established at least 12 weeks before screening including both endoscopic evidence and a histopathology report consistent with a diagnosis of CD 2. Moderately to severely active CD based on CDAI criteria, defined as baseline (Week I-0) CDAI score >=220 but <=450 and either mean daily SF count >=4, or mean daily AP score >=2 3. Moderately to severely active CD based on SES-CD criteria assessed by baseline (Week I-0) endoscopic evidence of active ileal and/or colonic CD as assessed during central review of the screening video ileocolonoscopy defined as a SES-CD >= 6 for participants with colonic or ileocolonic disease, and SES-CD >= 4 for participants with isolated ileal disease, based on the presence of ulceration in any 1 of the 5 ileocolonic segments 4. A female participant of childbearing potential must have a negative highly sensitive serum pregnancy test (beta-hCG) at screening and a negative urine pregnancy test at Week I-0 prior to administration of study intervention and agree to further pregnancy tests 5. Demonstrated an inadequate response, loss of response, or failure to tolerate previous conventional therapy (advanced drug therapy [ADT]-naïve) or advanced therapy defined as biologics and/or advanced oral agents for the treatment of CD (ADT-inadequate responder [IR]) as defined in the protocol |
| Key exclusion criteria | 1. Has complications of CD, such as symptomatic strictures or stenoses, short gut syndrome, or any other manifestation, that may require surgery while enrolled in the study and/or could impair the use of instruments (such as CDAI) to assess response to study intervention 2. Presence of a stoma or ostomy 3. Participants with presence of active fistulas may be included if there is no surgery needed 4. Colonic resection within 24 weeks before baseline or any other major surgery performed within 12 weeks before baseline 5. Presence on screening colonoscopy of adenomatous colon polyps outside of an area of known colitis not removed before randomization |
| Date of first enrolment | 01/11/2025 |
| Date of final enrolment | 01/08/2027 |
Locations
Countries of recruitment
- United Kingdom
- England
- Scotland
- Argentina
- Australia
- Belgium
- Brazil
- Canada
- China
- France
- Germany
- Greece
- Hungary
- India
- Israel
- Italy
- Japan
- Malaysia
- Netherlands
- Poland
- Portugal
- Romania
- Spain
- Switzerland
- Taiwan
Study participating centres
London
SW17 0RE
England
Rochdale Old Road
Bury
BL9 7TD
England
Great Maze Pond
London
SE1 9RT
England
Hills Road
Cambridge
CB2 0QQ
England
Glasgow
G4 0SF
Scotland
Warrington Road
Prescot
L35 5DR
England
Leytonstone
London
E11 1NR
England
Edgbaston
Birmingham
B15 2TH
England
Stepping Hill Hospital
Poplar Grove
Stockport
SK2 7JE
England
Results and Publications
| Individual participant data (IPD) Intention to share | Yes |
|---|---|
| IPD sharing plan summary | Available on request |
| IPD sharing plan | The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinicaltrials/ 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 |
Editorial Notes
13/11/2025: Internal review.
20/10/2025: Contact details updated.
16/10/2025: Ethics approval was added, and the date of first enrolment was changed from 16/10/2025 to 01/11/2025.
11/10/2025: ISRCTN received notification of combined HRA/MHRA approval for this trial on 11/10/2025.
07/08/2025: Trial's existence confirmed by NHS HRA.
