A Study to Assess the Efficacy and Safety of Induction Therapy With Afimkibart (RO7790121) in Participants With Moderately to Severely Active Crohn's Disease (SIBERITE-2)

 

Purpose of this study?

 

This Phase III, multicenter, double-blind, placebo-controlled study will evaluate the efficacy and safety of induction therapy with Afimkibart (also known as RO7790121) in participants with moderately to severely active Crohn's disease (CD).

 

Inclusion Criteria:

 

  • Confirmed diagnosis of CD
  • Moderately to severely active CD
  • Bodyweight >= 40 kilogram (kg)
  • Demonstrated inadequate response, loss of response and/or intolerance to at least one protocol-specified conventional or advanced CD therapy
  • Males and females of childbearing potential must meet protocol criteria for contraception requirements

 

 

Exclusion Criteria:

 

  • Current diagnosis of ulcerative colitis (UC) or indeterminate colitis, ischemic colitis, infectious colitis, radiation colitis, microscopic colitis
  • Participant with a history of >= 3 bowel resections (> 2 missing segments of the 5 following segments: terminal ilelium, right colon, transverse colon, sigmoid and left colon, and rectum)
  • Diagnosis of short gut or short bowel syndrome
  • Presence of an ileostomy, colostomy or ileoanal pouch
  • Participants with symptomatic bowel strictures, fulminant colitis, or toxic megacolon
  • Presence of abdominal or perianal abscess
  • Presence of rectovaginal, enterovaginal, high output enterocutaneous fistula, enterovesical fistulas or perianal fistulas with >3 openings
  • Participants with symptomatic bowel strictures, fulminant colitis, or toxic megacolon
  • Current diagnosis or suspicion of primary sclerosing cholangitis
  • Pregnancy or breastfeeding, or intention of becoming pregnant during the study
  • Any past or current evidence of cancer of gastrointestinal tract, definite low-grade or high-grade colonic dysplasia
  • History of non-gastrointestinal cancer, with the exception of adequately treated non-metastatic basal cell or squamous cell skin cancer or in situ cervical cancer
  • Evidence of infection with Clostridioides difficile (C. difficile; formerly known as Clostridium difficile), cytomegalovirus (CMV), human immunodeficiency virus (HIV), Hepatitis B (HBV), Hepatitis C (HCV) during screening
  • Has evidence of active tuberculosis (TB), latent TB not successfully treated (per local guidance) or inadequately treated TB
  • Has received protocol-specified prohibited medicines, including known exposure to any type of anti-TL1A therapy

 

Primary outcome measures:

 

  • Percentage of Participants with Clinical Remission per Crohn's Disease Activity Index (CDAI) Score [Time Frame: At Week 12]
  • Percentage of participants achieving a CDAI score of <150. The index is a weighted sum of scores on eight components: number of liquid or soft stools (stool frequency), abdominal pain, general well-being, number of complications, use of anti-diarrheal medication, presence of an abdominal mass, hematocrit, and percentage deviation from standard body weight. CDAI generally ranges from 0 to roughly 600, with higher values indicating greater activity.
  • Percentage of Participants with Endoscopic Response [Time Frame: At Week 12]
  • Percentage of participants achieving a decrease in Simple Endoscopic Score for Crohn's Disease (SES-CD) of >=50% from baseline. The SES-CD is a composite of four features of endoscopic activity (presence and size of ulcers, extent of ulcerated surface, extent of affected and presence and type of narrowings or stenosis) in up to five ileocolonic segments (terminal ileum, right colon, transverse colon, sigmoid and left colon, and rectum). Each feature is scored on a scale from 0 to 3, giving segment subscores of 0 to 12 points and a total SES-CD range of 0-60, with a higher value indicating greater severity.

 

Secondary outcome measures:

 

  • Percentage of Participants with Symptomatic Remission [Time Frame: At Week 12]
  • Percentage of participants with the daily number of liquid or very soft stools <=2.8 and the average of daily abdominal pain scores in the past week <=1, with neither being greater than baseline.
  • Percentage of Participants with Endoscopic Remission [Time Frame: At Week 12]
  • Percentage of participants with an SES-CD of 0 to 4 with a decrease from baseline >=2 and no subscore >1.
  • Percentage of Participants with Ulcer-free Endoscopy [Time Frame: At Week 12]
  • Percentage of participants with an SES-CD ulcerated surface subscore of 0.
  • Average of Daily Number of Liquid or Very Soft Stools in the Past Week (SF) [Time Frame: Baseline through Week 12]
  • Daily average number of liquid or very soft stools over 7 days.
  • Average of Daily Abdominal Pain Scores in the Past Week (APS) [Time Frame: Baseline through Week 12]
  • The average daily rating of abdominal pain in the past 7 days. The pain is assessed on a scale of 0-3 with 0 indicating no pain and 3 indicating severe pain.
  • Bowel Urgency [Time Frame: Baseline to Week 12]
  • Bowel urgency from baseline through week 12 and. Bowel urgency is a single-item self-reported assessment of sudden or immediate need to have a bowel movement in the past 24 hours. The item response is reported on a 4-point Likert scale, from "None" to "Severe."
  • Fatigue [Time Frame: Baseline to Week 12]
  • Fatigue, as measured by the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), from baseline to Week 12. FACIT-F is a 13-item self-reported assessment of fatigue. Each item response option indicates the degree to which a given statement describing the level or impact of fatigue applies in the past 7 days. Response options are graded on a 5-point Likert-type scale, from "Not at all" to "Very much."
  • Inflammatory Bowel Disease Questionnaire (IBDQ) Score [Time Frame: Baseline to Week 12]
  • Change in IBDQ score from baseline to week 12. The IBDQ is a 32-item questionnaire that measures four domains: bowel symptoms (10 questions); systemic symptoms (5 questions); emotional function (12 questions); and social function (5 questions). The total score ranges from 32-224, with a higher score indicating a better quality of life.
  • Percentage of Participants with Clinical Remission: Among Biomarker-Defined Subgroups of Participants [Time Frame: At Week 12]
  • Percentage of participants achieving a CDAI score of <150 at Week 12 in biomarker-defined subgroups. The index is a weighted sum of scores on eight components: number of liquid or soft stools (stool frequency), abdominal pain, general well-being, number of complications, use of anti-diarrheal medication, presence of an abdominal mass, hematocrit, and percentage deviation from standard body weight. CDAI generally ranges from 0 to roughly 600, with higher values indicating greater activity.
  • Percentage of Participants with Endoscopic Response: Among Biomarker-Defined Subgroups of Participants [Time Frame: At Week 12]
  • Percentage of participants achieving a decrease in SES-CD of >=50% from baseline. The SES-CD is a composite of four features of endoscopic activity (presence and size of ulcers, extent of ulcerated surface, extent of affected and presence and type of narrowings or stenosis) in up to five ileocolonic segments (terminal ileum, right colon, transverse colon, sigmoid and left colon, and rectum). Each feature is scored on a scale from 0 to 3, giving segment subscores of 0 to 12 points and a total SES-CD range of 0-60, with a higher value indicating greater severity.
  • Percentage of Participants with Clinical Response [Time Frame: At Week 12]
  • Percentage of participants with a decrease >=100 in CDAI from baseline.
  • Percentage of Participants with Symptomatic Response [Time Frame: At Week 12]
  • Percentage of participants with a decrease >=30% in both SF and APS, with neither being greater than baseline.
  • Overall Change in CD Symptoms [Time Frame: Baseline to Weeks 2, 6 and 12]
  • Overall change in CD symptoms, as measured by the Patient Global Impression of Change (PGIC) from baseline to Weeks 2, 6 and 12. PGIC measures overall change in Crohn's disease symptoms from "Much better" to "Much worse".
  • Overall Severity in CD Symptoms [Time Frame: Baseline to Weeks 2, 6 and 12]
  • Overall severity in CD symptoms, as measured by the Patient Global Impression of Severity (PGIS) from baseline to Weeks 2, 6 and 12. PGIS measures severity of Crohn's disease symptoms from "None" to "Very severe".
  • Change in General Well-being [Time Frame: Baseline through Week 12]
  • The average daily rating of general well-being in the past 7 days. Well-being is assessed on a scale of 0-4 with 0 indicating generally well and 4 indicating terrible.
  • Incidence and Severity of Adverse Events (AEs) [Time Frame: Up to 30 Weeks after Baseline]
  • Incidence and severity of AEs, including serious AEs, AEs leading to treatment discontinuation and AEs of special interest.
  • Presence of Draining Fistulas [Time Frame: Baseline through Week 12]
  • Fistulas will be assessed for draining or closed status, where closed fistulas will be assessed by the investigator as no longer draining.

 

Study Locations in Europe: Austria, Belgium, Bulgaria, Croatia, Czech republic, Denmark, France, Germany, Hungary, Italy, Netherlands, Poland, Portugal, Serbia, Slovakia, Spain, United Kingdom

 

 

 

Estimated Study Completion Date:  2033-04-30

 

Further information on clinicaltrials.gov – trial number NCT06819891