Crohn Disease
Conditions
Brief summary
The purpose of this study is to evaluate how-well icotrokinra works (clinical efficacy) and how safe it is (safety) in participants with moderately to severely active Crohn's disease (CD; a long-term condition causing severe inflammation of the intestinal tract).
Interventions
DRUGIcotrokinra
Icotrokinra will be administered orally, daily.
DRUGPlacebo
Matching placebo will be administered orally, daily.
Sponsors
Janssen Research & Development, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of CD established at least 12 weeks before screening including both endoscopic evidence and a histopathology report consistent with a diagnosis of CD * 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 * 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 * 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 * Demonstrated an inadequate response to, or failure to tolerate conventional therapy but naïve to advanced therapies (advanced drug therapy \[ADT\]-naïve) or inadequate response to (that is, primary or secondary nonresponse) or failure to tolerate advanced therapy defined as biologics and/or advanced oral agents for the treatment of CD- (ADT-inadequate responder \[IR\]) as defined in the protocol
Exclusion criteria
* 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 * Presence of a stoma or ostomy * Participants with presence of active fistulas may be included if there is no surgery needed * Colonic resection within 24 weeks before baseline or any other major surgery performed within 12 weeks before baseline * Presence on screening colonoscopy of adenomatous colon polyps outside of an area of known colitis not removed before randomization
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Induction Study 2: Number of Participants with Clinical Remission at Week 12 (Co-Primary Endpoint) | At Week 12 | Clinical remission is defined as CDAI score less than (\<) 150. CDAI scores range from 0 to approximately 600. Higher score indicates higher disease activity. |
| Induction Study 2: Number of Participants with Endoscopic Response at Week 12 (Co-Primary Endpoint) | At Week 12 | Endoscopic response is defined as greater than (\>) 50% improvement from baseline in Simple Endoscopic Score for Crohn's Disease (SES-CD) score or a decrease of at least 2 points in participants with a baseline score of 4 and isolated ileal disease. SES-CD score can range from 0 to 56. Higher scores indicating more severe disease. |
| Induction Study 1: Number of Participants with Clinical Response at Week 12 | At Week 12 | Clinical response is defined as a greater than or equal to (\>=) 100-point reduction from baseline in Crohn's Disease Activity Index (CDAI) score. CDAI scores range from 0 to approximately 600. Higher score indicates higher disease activity. |
| Maintenance Study: Number of Participants with Clinical Remission at Week 40 (Co-Primary Endpoint) | At Week 40 | Clinical remission is defined as CDAI score \< 150. CDAI scores range from 0 to approximately 600. Higher score indicates higher disease activity. |
| Maintenance Study: Number of Participants with Endoscopic Response at Week 40 (Co-Primary Endpoint) | At Week 40 | Endoscopic response is defined as \> 50% improvement from baseline in SES-CD score or a decrease of at least 2 points in participants with a baseline score of 4 and isolated ileal disease. SES-CD score can range from 0 to 56. Higher scores indicating more severe disease. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Induction Study 1: Number of Participants with Clinical Remission at Week 12 | At Week 12 | Clinical remission is defined as CDAI score \< 150. CDAI scores ranging from 0 to approximately 600. Higher score indicates higher disease activity. |
| Induction Study 1: Number of Participants with Endoscopic Response at Week 12 | At Week 12 | Endoscopic response is defined as \> 50% improvement from baseline in SES-CD score or a decrease of at least 2 points in participants with a baseline score of 4 and isolated ileal disease. SES-CD score can range from 0 to 56. Higher scores indicating more severe disease. |
| Induction Study 1: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) | Up to 4 weeks after last dose of study drug (i.e., up to Week 16) | An AE is any untoward medical occurrence in a clinical study participant administered a pharmaceutical (investigational or non-investigational) product that 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. |
| Induction Study 2: Number of Participants with Patient Reported Outcomes (PRO)-2 Remission at Week 12 | At Week 12 | PRO-2 remission is defined as an abdominal pain (AP) mean daily score less than or equal to (\<=) 1 and stool frequency (SF) mean daily score \<= 2.8, and no worsening of AP or SF from baseline. |
| Induction Study 2: Number of Participants with Clinical Response at Week 12 | At Week 12 | Clinical response is defined as a \>= 100-point reduction from baseline in CDAI score. |
| Induction Study 2: Number of Participants Reporting Both Clinical Remission and Endoscopic Response at Week 12 | At Week 12 | Clinical remission is defined as CDAI score \< 150. Endoscopic response is defined as \> 50% improvement from baseline in SES-CD score or a decrease of at least 2 points in participants with a baseline score of 4 and isolated ileal disease. This is a composite endpoint defined to measure achievement of both clinical remission and endoscopic response at the participant level. |
| Induction Study 2: Number of Participants with Clinical Response at Week 4 | At Week 4 | Clinical response is defined as a \>= 100-point reduction from baseline in CDAI score. |
| Induction Study 2: Number of Participants with Endoscopic Remission at Week 12 | At Week 12 | Endoscopic remission is defined as SES-CD \<= 4 with at least a 2-point reduction from baseline and no sub score \>1 in any individual component. |
| Induction Study 2: Number of Participants with Deep Remission at Week 12 | At Week 12 | Deep remission is a composite endpoint defined as achieving both clinical remission and endoscopic remission at the participant level. Clinical remission is defined as CDAI score \< 150-point. Endoscopic remission is defined as SES-CD \<= 4 with at least a 2-point reduction from baseline and no sub score \>1 in any individual component. |
| Induction Study 2: Number of Participants with Inflammatory Bowel Disease Questionnaire (IBDQ) Remission at Week 12 | At Week 12 | IBDQ remission is defined as IBDQ score \>= 170. IBDQ 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 (HRQoL) across 4 dimensional scores: bowel symptoms (loose stools, abdominal pain), systemic symptoms (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. |
| Induction Study 2: Number of Participants with Fatigue Response at Week 12 | At Week 12 | Fatigue response is defined as a \>= 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). Item responses are rated on a five-point scale ranging from "never" to "always". Higher scores indicate more fatigue. |
| Induction Study 2: Number of Participants with Clinical Remission at Week 4 | At Week 4 | Clinical remission is defined as CDAI score\< 150. |
| Induction Study 2: Number of Participants Reporting Both Histologic Remission and Endoscopic Remission at Week 12 | At Week 12 | Histologic remission is defined as a Robarts Histopathology Index score \<=3, where each of the items of lamina propria neutrophils, neutrophils in epithelium, and erosions or ulcerations must be equal to 0. Endoscopic remission is defined as SES-CD \<= 4 with at least a 2-point reduction from baseline and no sub score \>1 in any individual component. This is a composite endpoint defined as achieving both histologic remission and endoscopic remission at the participant level. |
| Induction Study 2: Number of Participants with AEs and SAEs | Up to 4 weeks after last dose of study drug (i.e., up to Week 16) | An AE is any untoward medical occurrence in a clinical study participant administered a pharmaceutical (investigational or non-investigational) product that 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. |
| Maintenance Study: Number of Participants with PRO-2 remission at Week 40 | At Week 40 | PRO-2 remission is defined as an abdominal pain (AP) mean daily score \<= 1 and stool frequency (SF) mean daily score \<= 2.8, and no worsening of AP or SF from baseline. |
| Maintenance Study: Number of Participants with Endoscopic Remission at Week 40 | At Week 40 | Endoscopic remission is defined as SES-CD \<= 4 with at least a 2-point reduction from baseline and no sub score \>1 in any individual component. |
| Maintenance Study: Number of Participants with 90-Day Corticosteroid-Free Clinical Remission at Week 40 | At Week 40 | 90-day corticosteroid-free clinical remission is defined as the clinical remission at the visit and not receiving corticosteroids for at least 90 days prior to the visit. Clinical remission is defined as CDAI score \< 150. |
| Maintenance Study: Number of Participants with Maintenance of Clinical Remission at Week 40 | At Week 40 | Participants with clinical remission at Week 40 among those with clinical remission at Week 0 of the maintenance study will be analyzed. Clinical remission is defined as CDAI score \< 150. |
| Maintenance Study: Number of Participants Reporting Both Clinical Remission and Endoscopic Response at Week 40 | At Week 40 | Clinical remission is defined as CDAI score \< 150. Endoscopic response is defined as \> 50% improvement from baseline in SES-CD score or a decrease of at least 2 points in participants with a baseline score of 4 and isolated ileal disease. This is a composite endpoint defined to measure achievement of both clinical remission and endoscopic response at the participant level. |
| Maintenance Study: Number of Participants with Deep Remission at Week 40 | At Week 40 | Deep remission is a composite endpoint defined as achieving both clinical remission and endoscopic remission at the participant level. Clinical remission is defined as CDAI score \< 150. Endoscopic remission is defined as SES-CD \<= 4 with at least a 2-point reduction from baseline and no sub score \>1 in any individual component. |
| Maintenance Study: Number of Participants Reporting Both Histologic Remission and Endoscopic Remission at Week 40 | At Week 40 | Histologic remission is defined as a Robarts Histopathology Index score \<=3, where each of the items of lamina propria neutrophils, neutrophils in epithelium, and erosions or ulcerations must be equal to 0. Endoscopic remission is defined as SES-CD \<= 4 with at least a 2-point reduction from baseline and no sub score \>1 in any individual component. This is a composite endpoint defined as achieving both histologic remission and endoscopic remission at the participant level. |
| Maintenance Study: Number of Participants with IBDQ Remission at Week 40 | At Week 40 | IBDQ remission is defined as IBDQ score \>= 170. IBDQ is a validated, 32-item, self-reported questionnaire for participants with IBD that will be used to evaluate the disease-specific HRQoL across 4 dimensional scores: bowel symptoms (loose stools, abdominal pain), systemic symptoms (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. |
| Maintenance Study: Number of Participants with Fatigue Response at Week 40 | At Week 40 | Fatigue response is defined as a \>= 7 point reduction in the 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). Item responses are rated on a five-point scale ranging from "never" to "always". Higher scores indicate more fatigue. |
| Maintenance Study : Number of Participants with AEs and SAEs | Up to 4 weeks after last dose of study drug (i.e., up to Week 44) | An AE is any untoward medical occurrence in a clinical study participant administered a pharmaceutical (investigational or non-investigational) product that 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. |
Countries
Argentina, Australia, Belgium, Brazil, Canada, China, Czechia, France, Germany, Greece, Hungary, India, Israel, Italy, Japan, Malaysia, Netherlands, Poland, Portugal, Romania, South Korea, Spain, Sweden, Switzerland, Taiwan, Turkey (Türkiye), United Kingdom, United States
Contacts
CONTACTStudy Contact
STUDY_DIRECTORJanssen Research & Development, LLC Clinical Trial
Janssen Research & Development, LLC
Outcome results
None listed