Moderately to Severely Active Crohns Disease
Conditions
Brief summary
This Phase III, multicenter, double-blind, placebo-controlled treat-through study will evaluate the efficacy and safety of induction and maintenance therapy with Afimkibart (also known as RO7790121) in participants with moderately to severely active Crohn's disease (CD).
Interventions
DRUGAfimkibart
Afimkibart will be administered as IV infusion. Afimkibart will be administered as SC injection.
DRUGPlacebo
Placebo matching IV afimkibart. Placebo matching SC afimkibart.
Sponsors
Hoffmann-La Roche
Chugai Pharmaceutical
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
16 Years to 80 Years
Healthy volunteers
No
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 * 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants with Clinical Remission per Crohn's Disease Activity Index (CDAI) Score | At Week 52 | 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 | At Week 52 | 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
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants with Clinical Remission | 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 | 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 Symptomatic Remission | 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 | 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 | 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) | 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) | 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. |
| Percentage of Participants with Corticosteroid-free Clinical Remission | At Week 52 | Percentage of participants with clinical remission at Week 52 and no use of corticosteroids for CD at least 8 weeks prior to Week 52. |
| Maintenance of Clinical Remission | At Weeks 12 and 52 | Percentage of participants with clinical remission at both Weeks 12 and 52. |
| Maintenance of Endoscopic Response | At Weeks 12 and 52 | Percentage of participants with endoscopic response at both Weeks 12 and 52. |
| Percentage of Participants with Clinical Remission and Endoscopic Remission at Week 52 | At Week 52 | Percentage of participants achieving a CDAI score of \<150 and SES-CD of 0 to 4 with a decrease from baseline \>=2 and no subscore \>1 at Week 52. |
| Bowel Urgency | Baseline through Week 12 and Week 52 | Bowel urgency from baseline through week 12 and week 52. 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 | Baseline to Week 12 and Week 52 | Fatigue, as measured by the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), from baseline to Week 12 and Week 52. 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 | Baseline to Week 12 and Week 52 | Change in IBDQ score from baseline to week 12 and 52. 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 | 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 | 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 | At Week 12 | Percentage of participants with a decrease \>=100 in CDAI from baseline. |
| Percentage of Participants with Symptomatic Response | 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 | Baseline to Weeks 2, 6, 12 and 52 | Overall change in CD symptoms, as measured by the Patient Global Impression of Change (PGIC) from baseline to Weeks 2, 6, 12 and 52. PGIC measures overall change in Crohn's disease symptoms from "Much better" to "Much worse". |
| Overall Severity in CD Symptoms | Baseline to Weeks 2, 6, 12 and 52 | Overall severity in CD symptoms, as measured by the Patient Global Impression of Severity (PGIS) from baseline to Weeks 2, 6, 12 and 52. PGIS measures severity of Crohn's disease symptoms from "None" to "Very severe". |
| Change in General Well-being | Baseline through Week 52 | 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) | Up to 70 Weeks after Baseline | Incidence and severity of AEs, including serious AEs, AEs leading to treatment discontinuation and AEs of special interest. |
| Percentage of Participants with a Presence of Draining Fistulas | Baseline through Week 12 and Week 52 | Fistulas will be assessed for draining or closed status, where closed fistulas will be assessed by the investigator as no longer draining. |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, Chile, China, Colombia, Croatia, Czechia, Denmark, Dominican Republic, France, Germany, Guatemala, Hungary, India, Israel, Italy, Japan, Mexico, Netherlands, Panama, Poland, Portugal, Puerto Rico, Romania, Serbia, Slovakia, South Korea, Spain, Taiwan, Thailand, United Arab Emirates, United Kingdom, United States
Contacts
CONTACTReference Study ID Number: GA45331 https://forpatients.roche.com/ No attachments to email below.
CONTACTFastest response: use the inquiry form. https://www.gene.com/contact-us/submit-medical-inquiry
STUDY_DIRECTORClinical Trials
Hoffmann-La Roche
Outcome results
None listed