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

Phase 3RecruitingNCT06819878

Hoffmann-La Roche600 enrolled

Overview

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).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

600

Conditions

Moderately to Severely Active Crohns Disease

Interventions

AfimkibartDRUG

Afimkibart will be administered as IV infusion. Afimkibart will be administered as SC injection.

PlaceboDRUG

Placebo matching IV afimkibart. Placebo matching SC afimkibart.

Eligibility

Sex: ALLMin age: 16 YearsMax age: 80 Years

Medical Language ↔ Plain English

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

Locations (374)

Outcomes

Primary Outcomes

Percentage of Participants with Clinical Remission per Crohn's Disease Activity Index (CDAI) Score

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.

Time frame: At Week 52

Percentage of Participants with Endoscopic Response

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.

Time frame: At Week 52

Secondary Outcomes

Percentage of Participants with Clinical Remission

Time frame: At Week 12

Percentage of Participants with Endoscopic Response

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.

Central Contacts

Reference Study ID Number: GA45331 https://forpatients.roche.com/ No attachments to email below.

CONTACT

888-662-6728 (U.S. and Canada)global-roche-genentech-trials@gene.com

Fastest response: use the inquiry form. https://www.gene.com/contact-us/submit-medical-inquiry

CONTACT

Data from ClinicalTrials.gov

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Digestive Health Specialists of the Southeast (Gastroenterology Associates of Dothan) - Dothan

Dothan, Alabama, United States

RECRUITING

Mayo Clinic Hospital

Phoenix, Arizona, United States

RECRUITING

Arizona Digestive Health, P.C (ADH)

Sun City, Arizona, United States

RECRUITING

University of Arizona-CATS Research Center

Tucson, Arizona, United States

RECRUITING

Valley View Internal Medicine

Garden Grove, California, United States

RECRUITING

310 Clinical Research

Inglewood, California, United States

RECRUITING

UCSD Medical Center

La Jolla, California, United States

RECRUITING

University of California San Diego

La Jolla, California, United States

RECRUITING

Gastro Care Associates

Lancaster, California, United States

RECRUITING

Om Research LLC

Lancaster, California, United States

RECRUITING

...and 364 more locations

Time frame: At Week 12

Percentage of Participants with Symptomatic Remission

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.

Time frame: At Week 12

Percentage of Participants with Endoscopic Remission

Percentage of participants with an SES-CD of 0 to 4 with a decrease from baseline \>=2 and no subscore \>1.

Time frame: At Week 12

Percentage of Participants with Ulcer-free Endoscopy

Percentage of participants with an SES-CD ulcerated surface subscore of 0.

Time frame: At Week 12

Average of Daily Number of Liquid or Very Soft Stools in the Past Week (SF)

Daily average number of liquid or very soft stools over 7 days.

Time frame: Baseline through Week 12

Average of Daily Abdominal Pain Scores in the Past Week (APS)

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.

Time frame: Baseline through Week 12

Percentage of Participants with Endoscopic Remission

Percentage of participants with SES-CD=0 to 4 with decrease from baseline \>=2 and no subscore \>1 .

Time frame: At Week 52

Percentage of Participants with Symptomatic Remission

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.

Time frame: At Week 52

Percentage of Participants with Corticosteroid-free Clinical Remission

Percentage of participants with clinical remission at Week 52 and no use of corticosteroids for CD at least 8 weeks prior to Week 52.

Time frame: At Week 52

Maintenance of Clinical Remission

Percentage of participants with clinical remission at both Weeks 12 and 52.

Time frame: At Weeks 12 and 52

Maintenance of Endoscopic Response

Percentage of participants with endoscopic response at both Weeks 12 and 52.

Time frame: At Weeks 12 and 52

Percentage of Participants with Clinical Remission and Endoscopic Remission 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.

Time frame: At Week 52

Percentage of Participants with Ulcer-free Endoscopy

Percentage of participants with an SES-CD ulcerated surface subscore of 0.

Time frame: At Week 52

Bowel Urgency

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."

Time frame: Baseline through Week 12 and Week 52

Fatigue

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."

Time frame: Baseline to Week 12 and Week 52

Inflammatory Bowel Disease Questionnaire (IBDQ) Score

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.

Time frame: Baseline to Week 12 and Week 52

Percentage of Participants with Clinical Remission: Among Biomarker-Defined Subgroups of Participants

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.

Time frame: At Week 12

Percentage of Participants with Clinical Remission: Among Biomarker-Defined Subgroups of Participants

Percentage of participants achieving a CDAI score of \<150 at Week 52 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.

Time frame: At Week 52

Percentage of Participants with Endoscopic Response: Among Biomarker-Defined Subgroups of Participants

Time frame: At Week 12

Percentage of Participants with Endoscopic Response: Among Biomarker-Defined Subgroups of Participants

Time frame: At Week 52

Percentage of Participants with Clinical Response

Percentage of participants with a decrease \>=100 in CDAI from baseline.

Time frame: At Week 12

Percentage of Participants with Symptomatic Response

Percentage of participants with a decrease \>=30% in both SF and APS, with neither being greater than baseline.

Time frame: At Week 12

Overall Change in CD Symptoms

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".

Time frame: Baseline to Weeks 2, 6, 12 and 52

Overall Severity in CD Symptoms

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".

Time frame: Baseline to Weeks 2, 6, 12 and 52

Change in General Well-being

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.

Time frame: Baseline through Week 52

Incidence and Severity of Adverse Events (AEs)

Incidence and severity of AEs, including serious AEs, AEs leading to treatment discontinuation and AEs of special interest.

Time frame: Up to 70 Weeks after Baseline

Percentage of Participants with a Presence of Draining Fistulas

Fistulas will be assessed for draining or closed status, where closed fistulas will be assessed by the investigator as no longer draining.

Time frame: Baseline through Week 12 and Week 52