Colitis, Ulcerative
Conditions
Brief summary
The purpose of this protocol is to evaluate the efficacy (how well it works), safety and tolerability of oral icotrokinra as therapy in adult and adolescent 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 tiny open ulcers).
Interventions
DRUGIcotrokinra
Icotrokinra tablet will be administered orally.
DRUGPlacebo
Placebo tablet will be administered orally.
Sponsors
Janssen Research & Development, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
This study is double-blind for adults and open-label for adolescent participants.
Intervention model description
Parallel assignment applies to adult participants only.
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
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 a 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 * An endoscopy subscore greater than or equal to (\>=) 2 as obtained during central review of the screening video endoscopy * Adolescent Participants: body weight must be \>= 40 kilograms (kg) at baseline (Week I-0) * Adult female participants of childbearing potential and all adolescent female participants must have a negative highly sensitive serum pregnancy test (beta-human chorionic gonadotropin \[β-hCG\]) 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 are naïve to advanced therapies (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 UC (ADT-inadequate responder \[IR\]) as defined in the protocol
Exclusion criteria
* 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 * Presence of a stoma * Presence or history of a fistula * Colonic resection within 24 weeks before baseline or any other intra-abdominal or other major surgery performed within 12 weeks before baseline * History of extensive colonic resection (that is, less than \[\<\] 30 centimeter \[cm\] of colon remaining) or colonic resection that could impair the use of disease severity assessments (for example Mayo Score) to assess response to study intervention
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Double-blind (DB) Induction Study: Percentage of Adult Participants in Clinical Remission at Week I-12 | At Week I-12 | Percentage of adult participants in clinical remission at Week I-12 will be reported. Clinical remission is defined as stool frequency subscore of 0 or 1, a rectal bleeding subscore of 0, and an endoscopy subscore of 0 or 1. |
| DB Maintenance Study: Percentage of Adult Participants in Clinical Remission at Week M-40 | At Week M-40 | Percentage of adult participants in clinical remission at Week M-40 will be reported. Clinical remission is defined as stool frequency subscore of 0 or 1, a rectal bleeding subscore of 0, and an endoscopy subscore of 0 or 1. |
| Open-Label (OL) Maintenance Phase: Percentage of Adolescent Participants in Clinical Remission at Week M-40 | At Week M-40 | Percentage of adolescent participants in clinical remission at Week M-40 will be reported. Clinical remission is defined as stool frequency subscore of 0 or 1, a rectal bleeding subscore of 0, and an endoscopy subscore of 0 or 1. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| DB Induction Study: Percentage of Adult Participants in Clinical Response at Week I-12 | At Week I-12 | Percentage of adult participants in clinical response at Week I-12 will be reported. Clinical response is defined as a decrease from baseline in the modified Mayo score by greater than or equal to (\>=) 30 percent (%) 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. |
| DB Induction Study: Percentage of Adult Participants with Endoscopic Improvement at Week I-12 | At Week I-12 | Percentage of adult participants with endoscopic improvement at Week I-12 will be reported. Endoscopic improvement is defined as an endoscopy subscore of 0 or 1. |
| DB Induction Study: Percentage of Adult Participants in Symptomatic Remission at Week I-12 | At Week I-12 | Percentage of adult participants in symptomatic remission at Week I-12 will be reported. Symptomatic remission is defined as a stool frequency subscore of 0 or 1 and a rectal bleeding subscore of 0. |
| DB Induction Study: Percentage of Adult Participants with Inflammatory Bowel Disease Questionnaire (IBDQ) Remission at Week I-12 | At Week I-12 | Percentage of adult participants with IBDQ remission at Week I-12 will be reported. IBDQ remission is defined as an IBDQ total score of \>= 170. The IBDQ is a validated, 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 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. |
| DB Induction Study: Percentage of Adult Participants with Histologic-Endoscopic Mucosal Improvement (HEMI) at Week I-12 | At Week I-12 | Percentage of adult participants with HEMI at Week I-12 will be reported. HEMI is defined as achieving a combination of histologic improvement and endoscopic improvement. Histologic improvement is defined as neutrophil infiltration in less than (\<) 5% of crypts, no crypt destruction, and no erosions, ulcerations, or granulation tissue according to the Geboes grading system. Endoscopic improvement is defined as an endoscopy sub-score of 0 or 1. |
| DB Induction Study: Percentage of Adult Participants with Fatigue Response at Week I-12 | At Week I-12 | Percentage of adult participants with fatigue response at Week I-12 will be reported. Fatigue response is defined as a \>= 7-point reduction in the patient-reported outcomes measurement information system (PROMIS)-fatigue Short Form (SF)-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). |
| DB Induction Study: Percentage of Adult Participants in Symptomatic Remission at Week I-4 | At Week I-4 | Percentage of adult participants in symptomatic remission at Week I-4 will be reported. Symptomatic remission is defined as a stool frequency subscore of 0 or 1 and a rectal bleeding subscore of 0. |
| DB Induction Study: Percentage of Adult Participants in Endoscopic Remission at Week I-12 | At Week I-12 | Percentage of adult participants in endoscopic remission at Week I-12 will be reported. Endoscopic remission is defined as an endoscopy subscore of 0. |
| DB Induction Study: Percentage of Adult Participants with No Bowel Urgency at Week I-12 | At Week I-12 | Percentage of adult participants with no bowel urgency at Week I-12 will be reported using the ulcerative colitis patient-reported outcomes signs and symptoms (UC-PRO/SS). The UC-PRO/SS is a 9-item measure that was developed to standardize the quantification of gastrointestinal (GI) signs and symptoms of UC through direct report from participant ratings. The module includes both bowel signs and symptoms and abdominal symptoms, with a recall period of 24 hours. |
| DB Induction Study: Percentage of Adult Participants with No Abdominal Pain at Week I-12 | At Week I-12 | Percentage of adult participants with no abdominal pain at Week I-12 will be reported using the UC-PRO/SS. The UC-PRO/SS is a 9-item measure that was developed to standardize the quantification of GI signs and symptoms of UC through direct report from participant ratings. The module includes both bowel signs and symptoms and abdominal symptoms, with a recall period of 24 hours. |
| DB Induction Study: Percentage of Adult Participants with No Bowel Incontinence at Week I-12 | At Week I-12 | Percentage of adult participants with no bowel incontinence at Week I-12 will be reported using the UC-PRO/SS. The UC-PRO/SS is a 9-item measure that was developed to standardize the quantification of GI signs and symptoms of UC through direct report from participant ratings. The module includes both bowel signs and symptoms and abdominal symptoms, with a recall period of 24 hours. |
| DB Induction Study: Percentage of Adult Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) | Up to Week I-12 | Percentage of adult participants with AEs and SAEs will be reported. 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. A 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, is medically important. |
| DB Maintenance Study: Percentage of Adult Participants with Endoscopic Improvement at Week M-40 | At Week M-40 | Percentage of adult participants with endoscopic improvement at Week M-40 will be reported. Endoscopic improvement is defined as an endoscopy subscore of 0 or 1. |
| DB Maintenance Study: Percentage of Adult Participants in Symptomatic Remission at Week M-40 | At Week M-40 | Percentage of adult participants in symptomatic remission at Week M-40 will be reported. Symptomatic remission is defined as a stool frequency subscore of 0 or 1 and a rectal bleeding subscore of 0. |
| DB Maintenance Study: Percentage of Adult Participants with 90-day Corticosteroid-free Clinical Remission at Week M-40 | At Week M-40 | Percentage of adult participants with 90-day corticosteroid-free clinical remission at Week M-40 will be reported. 90-day corticosteroid-free clinical remission is defined as the clinical remission at the visit and not receiving corticosteroids for 90 days prior to the visit. |
| DB Maintenance Study: Percentage of Adult Participants with HEMI at Week M-40 | At Week M-40 | Percentage of adult participants with HEMI at Week M-40 will be reported. HEMI is defined as achieving a combination of histologic improvement and endoscopic improvement. Histologic improvement is defined as neutrophil infiltration in \< 5% of crypts, no crypt destruction, and no erosions, ulcerations, or granulation tissue according to the Geboes grading system. Endoscopic improvement is defined as an endoscopy sub-score of 0 or 1. |
| DB Maintenance Study: Percentage of Adult Participants with IBDQ Remission at Week M-40 | At Week M-40 | Percentage of adult participants with IBDQ remission at Week M-40 will be reported. IBDQ remission is defined as an IBDQ total score of \>= 170. The 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. |
| DB Maintenance Study: Percentage of Adult Participants in Endoscopic Remission at Week M-40 | At Week M-40 | Percentage of adult participants in endoscopic remission at Week M-40 will be reported. Endoscopic remission is defined as an endoscopy subscore of 0. |
| DB Maintenance Study: Percentage of Adult Participants in Clinical Remission at Week M-40 Among the Participants who had Achieved Clinical Remission at Maintenance Baseline | At Week M-40 | Percentage of adult participants in clinical remission at Week M-40 among the participants who had achieved clinical remission at maintenance baseline will be reported. Clinical remission is defined as stool frequency subscore of 0 or 1, a rectal bleeding subscore of 0, and an endoscopy subscore of 0 or 1. |
| DB Maintenance Study: Percentage of Adult Participants in Histologic-Endoscopic Mucosal Remission at Week M-40 | At Week M-40 | Percentage of adult participants in histologic-endoscopic mucosal remission at Week M-40 will be reported. Histologic-endoscopic mucosal remission is defined as achieving a combination of histologic remission and endoscopic remission. Histologic remission is defined as the 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. Endoscopic remission is defined as an endoscopy subscore of 0. |
| DB Maintenance Study: Percentage of Adult Participants with Fatigue Response at Week M-40 | At Week M-40 | Percentage of adult participants with fatigue response at Week M-40 will be reported. Fatigue response is defined as a \>= 7-point reduction in the PROMIS-fatigue SF-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). |
| DB Maintenance Study: Percentage of Adult Participants with Disease Clearance at Week M-40 | At Week M-40 | Percentage of adult participants with disease clearance at Week M-40 will be reported. Disease clearance is defined as a composite of symptomatic remission and histologic-endoscopic mucosal remission. Symptomatic remission is defined as a stool frequency subscore of 0 or 1 and a rectal bleeding subscore of 0. Histologic-endoscopic mucosal remission is defined as achieving a combination of histologic remission and endoscopic remission. |
| DB Maintenance Study: Percentage of Adult Participants with No Bowel Urgency at Week M-40 | At Week M-40 | Percentage of adult participants with no bowel urgency at Week M-40 will be reported using the UC-PRO/SS. The UC-PRO/SS is a 9-item measure that was developed to standardize the quantification of GI signs and symptoms of UC through direct report from participant ratings. The module includes both bowel signs and symptoms and abdominal symptoms, with a recall period of 24 hours. |
| DB Maintenance Study: Percentage of Adult Participants with No Abdominal Pain at Week M-40 | At Week M-40 | Percentage of adult participants with no abdominal pain at Week M-40 will be reported using the UC-PRO/SS. The UC-PRO/SS is a 9-item measure that was developed to standardize the quantification of GI signs and symptoms of UC through direct report from participant ratings. The module includes both bowel signs and symptoms and abdominal symptoms, with a recall period of 24 hours. |
| DB Maintenance Study: Percentage of Adult Participants with No Bowel Incontinence at Week M-40 | At Week M-40 | Percentage of adult participants with no bowel incontinence at Week M-40 will be reported using the UC-PRO/SS. The UC-PRO/SS is a 9-item measure that was developed to standardize the quantification of GI signs and symptoms of UC through direct report from participant ratings. The module includes both bowel signs and symptoms and abdominal symptoms, with a recall period of 24 hours. |
| DB Maintenance Study: Percentage of Adult Participants with AEs and SAEs | Up to Week M-40 | Percentage of adult participants with AEs and SAEs will be reported. 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. A 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. |
| OL Induction Phase: Percentage of Adolescent Participants in Clinical Response at Week I-12 | At Week I-12 | Percentage of adolescent participants in clinical response at Week I-12 will be reported. Clinical response is defined as a decrease from baseline in the modified Mayo score by greater than or equal to (\>=) 30 percent (%) 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. |
| OL Induction Phase: Percentage of Adolescent Participants in Clinical Remission at Week I-12 | At Week I-12 | Percentage of adolescent participants in clinical remission at Week I-12 will be reported. Clinical remission is defined as stool frequency subscore of 0 or 1, a rectal bleeding subscore of 0, and an endoscopy subscore of 0 or 1. |
| OL Induction Phase: Percentage of Adolescent Participants with HEMI at Week I-12 | At Week I-12 | Percentage of adolescent participants with HEMI at Week I-12 will be reported. HEMI is defined as achieving a combination of histologic improvement and endoscopic improvement. Histologic improvement is defined as neutrophil infiltration in less than (\<) 5% of crypts, no crypt destruction, and no erosions, ulcerations, or granulation tissue according to the Geboes grading system. Endoscopic improvement is defined as an endoscopy sub-score of 0 or 1. |
| OL Induction Phase: Percentage of Adolescent Participants with Endoscopic Improvement at Week I-12 | At Week I-12 | Percentage of adolescent participants with endoscopic improvement at Week I-12 will be reported. Endoscopic improvement is defined as an endoscopy subscore of 0 or 1. |
| OL Induction Phase: Percentage of Adolescent Participants in Symptomatic Remission at Week I-12 | At Week I-12 | Percentage of adolescent participants in symptomatic remission at Week I-12 will be reported. Symptomatic remission is defined as a stool frequency subscore of 0 or 1 and a rectal bleeding subscore of 0. |
| OL Induction Phase: Percentage of Adolescent Participants in Endoscopic Remission at Week I-12 | At Week I-12 | Percentage of adolescent participants in endoscopic remission at Week I-12 will be reported. Endoscopic remission is defined as an endoscopy subscore of 0. |
| OL Induction Phase: Percentage of Adolescent Participants in Pediatric Ulcerative Colitis Activity Index (PUCAI) Remission at Week I-12 | At Week I-12 | Percentage of adolescent participants in PUCAI remission at Week I-12 will be reported. PUCAI remission is defined as a PUCAI score \<10. The PUCAI is a non-invasive instrument for measuring disease activity in adolescents with UC. Disease activity is determined as a score based on evaluation of abdominal pain, rectal bleeding, stool consistency, number of stools, nocturnal bowel movement, and activity level. The PUCAI score ranges from 0 to 85. |
| OL Induction Phase: Percentage of Adolescent Participants with AEs and SAEs | Up to Week I-12 | Percentage of adolescent participants with AEs and SAEs will be reported. 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. A 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. |
| OL Maintenance Study: Percentage of Adolescent Participants with Endoscopic Improvement at Week M-40 | At Week M-40 | Percentage of adolescent participants with endoscopic improvement at Week M-40 will be reported. Endoscopic improvement is defined as an endoscopy subscore of 0 or 1. |
| OL Maintenance Phase: Percentage of Adolescent Participants in Symptomatic Remission at Week M-40 | At Week M-40 | Percentage of adolescent participants in symptomatic remission at Week M-40 will be reported. Symptomatic remission is defined as a stool frequency subscore of 0 or 1 and a rectal bleeding subscore of 0. |
| OL Maintenance Phase: Percentage of Adolescent Participants in 90-day Corticosteroid-free Clinical Remission at Week M-40 | At Week M-40 | Percentage of adolescent participants in 90-day corticosteroid-free clinical remission at Week M-40 will be reported. 90-day corticosteroid-free clinical remission is defined as the clinical remission at the visit and not receiving corticosteroids for 90 days prior to the visit. |
| OL Maintenance Phase: Percentage of Adolescent Participants with HEMI at Week M-40 | At Week M-40 | Percentage of adolescent participants with HEMI at Week M-40 will be reported. HEMI is defined as achieving a combination of histologic improvement and endoscopic improvement. Histologic improvement is defined as neutrophil infiltration in \< 5% of crypts, no crypt destruction, and no erosions, ulcerations, or granulation tissue according to the Geboes grading system. Endoscopic improvement is defined as an endoscopy sub-score of 0 or 1. |
| OL Maintenance Phase: Percentage of Adolescent Participants with Histologic-Endoscopic Mucosal Remission at Week M-40 | At Week M-40 | Percentage of adolescent participants with histologic-endoscopic mucosal remission at Week M-40 will be reported. Histologic-endoscopic mucosal remission is defined as achieving a combination of histologic remission and endoscopic remission. Histologic remission is defined as the 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. Endoscopic remission is defined as an endoscopy subscore of 0. |
| OL Maintenance Phase: Percentage of Adolescent Participants with Endoscopic Remission at Week M-40 | At Week M-40 | Percentage of adolescent participants with endoscopic remission at Week M-40 will be reported. Endoscopic remission is defined as an endoscopy subscore of 0. |
| OL Maintenance Phase: Percentage of Adolescent Participants in Clinical Remission at Week M-40 Among the Participants who had Achieved Clinical Remission at Maintenance Baseline | At Week M-40 | Percentage of adolescent participants in clinical remission at Week M-40 among the participants who had achieved clinical remission at maintenance baseline will be reported. Clinical remission is defined as stool frequency subscore of 0 or 1, a rectal bleeding subscore of 0, and an endoscopy subscore of 0 or 1. |
| OL Maintenance Phase: Percentage of Adolescent Participants in Clinical Response at Week M-40 Among the Participants who had Achieved Clinical Response at Maintenance Baseline | At Week M-40 | Percentage of adolescent participants in clinical response at Week M-40 among the participants who had achieved clinical response at maintenance baseline will be reported. Clinical response is 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. |
| OL Maintenance Phase: Percentage of Adolescent Participants in PUCAI Remission at Week-40 | At Week M-40 | Percentage of adolescent participants in PUCAI remission at Week M-40 will be reported. PUCAI remission is defined as a PUCAI score \<10. The PUCAI is a non-invasive instrument for measuring disease activity in adolescents with UC. Disease activity is determined as a score based on evaluation of abdominal pain, rectal bleeding, stool consistency, number of stools, nocturnal bowel movement, and activity level. The PUCAI score ranges from 0 to 85. |
| OL Maintenance Phase: Percentage of Adolescent Participants with AEs and SAEs | Up to Week M-40 | Percentage of adolescent participants with AEs and SAEs will be reported. 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. A 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