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

Phase 3
Recruiting
Conditions
Moderately to Severely Active Crohns Disease
Interventions
Drug: Placebo
Registration Number
NCT06819878
Lead Sponsor
Hoffmann-La Roche
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 RO7790121 in participants with moderately to severely active Crohn's disease (CD).

Detailed Description

Not available

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
600
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 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
  • Past or current evidence of definite low-grade or high-grade colonic dysplasia or adenomas or neoplasia not completely removed
  • History of malignancy within 5 years, with the exception of malignancies adequately treated with resection for non-metastatic basal cell or squamous cell 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)
  • 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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Arm 3: PlaceboPlaceboParticipants will receive placebo IV followed by placebo SC.
Arm 1: RO7790121RO7790121Participants will receive RO7790121 intravenously (IV) followed by RO7790121 subcutaneous (SC) injection.
Arm 2: RO7790121RO7790121Participants will receive RO7790121 IV followed by RO7790121 SC injection.
Primary Outcome Measures
NameTimeMethod
Percentage of Participants with Endoscopic ResponseAt 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.

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

Secondary Outcome Measures
NameTimeMethod
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 RemissionAt 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.

Inflammatory Bowel Disease Questionnaire (IBDQ) ScoreBaseline 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 RemissionAt 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 Symptomatic RemissionAt Week 52

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 Ulcer-free EndoscopyAt Week 52

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.

Maintenance of Clinical RemissionAt Weeks 12 and 52

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

Maintenance of Endoscopic ResponseAt Weeks 12 and 52

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

Percentage of Participants with Endoscopic ResponseAt 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 Endoscopic RemissionAt Week 52

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

Bowel UrgencyBaseline 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."

Percentage of Participants with Clinical Remission and Endoscopic Remission at Week 52At 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.

FatigueBaseline 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."

Percentage of Participants with Clinical Remission: Among Biomarker-Defined Subgroups of ParticipantsAt Week 52

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.

Percentage of Participants with Clinical ResponseAt Week 12

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

Percentage of Participants with Endoscopic Response: Among Biomarker-Defined Subgroups of ParticipantsAt Week 52

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.

Overall Change in CD SymptomsBaseline 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".

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 Symptomatic ResponseAt Week 12

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

Percentage of Participants with a Presence of Draining FistulasBaseline 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.

Overall Severity in CD SymptomsBaseline 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-beingBaseline 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.

Trial Locations

Locations (81)

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

🇺🇸

Dothan, Alabama, United States

Arizona Digestive Health, P.C (ADH)

🇺🇸

Sun City, Arizona, United States

Valley View Internal Medicine

🇺🇸

Garden Grove, California, United States

310 Clinical Research

🇺🇸

Inglewood, California, United States

Gastro Care Associates

🇺🇸

Lancaster, California, United States

Om Research LLC

🇺🇸

Lancaster, California, United States

Peak Gastroenterology Surgery Center

🇺🇸

Lone Tree, Colorado, United States

Access Research Institute

🇺🇸

Brooksville, Florida, United States

Hi Tech and Global Research, LLC

🇺🇸

Coral Gables, Florida, United States

Clinical Research of Osceola, LLC

🇺🇸

Kissimmee, Florida, United States

Florida Research Institute - Lakewood

🇺🇸

Lakewood Ranch, Florida, United States

LCC Medical Research Institute, LLC

🇺🇸

Miami, Florida, United States

Ambert Medical Research

🇺🇸

Miami, Florida, United States

Nodal Medical Center Research - NMC

🇺🇸

Tampa, Florida, United States

Guardian Angel Research Center, LLC

🇺🇸

Tampa, Florida, United States

Theia Clinical Research Centers, LLC

🇺🇸

Temple Terrace, Florida, United States

Digestive Healthcare of Georgia

🇺🇸

Atlanta, Georgia, United States

Atlanta Gastroenterology Associates

🇺🇸

Atlanta, Georgia, United States

Gastroenterology Associates of Central Georgia

🇺🇸

Macon, Georgia, United States

Grand Teton Research Group, PLLC

🇺🇸

Idaho Falls, Idaho, United States

Illinois Gastroenterology Group-Glenview powered by GI Alliance

🇺🇸

Glenview, Illinois, United States

GI Alliance - Gurnee

🇺🇸

Gurnee, Illinois, United States

Gastroenterology Health Partners, PLLC

🇺🇸

Louisville, Kentucky, United States

Kansas Gastroenterology, LLC under Clinical Trials Network

🇺🇸

Wichita, Kansas, United States

Tri-State Gastroenterology Associates

🇺🇸

Crestview Hills, Kentucky, United States

Brigham and Women's Hospital

🇺🇸

Boston, Massachusetts, United States

Gastroenterology Associates and Endoscopy Center of North Mississippi

🇺🇸

Oxford, Mississippi, United States

Delta Gastroenterology & Endoscopy Center

🇺🇸

Southaven, Mississippi, United States

DiGiovanna Inst for Med Ed&Res

🇺🇸

North Massapequa, New York, United States

Queens Village Medical Care

🇺🇸

Queens Village, New York, United States

Gastroenterology Group of Rochester under CTNx

🇺🇸

Rochester, New York, United States

Monroe Biomedical Research

🇺🇸

Monroe, North Carolina, United States

Dayton Gastroenterology, Inc.

🇺🇸

Beavercreek, Ohio, United States

Ohio Gastroenterology Group

🇺🇸

Columbus, Ohio, United States

The Ohio State University Wexner Medical Center

🇺🇸

Columbus, Ohio, United States

Gastro Intestinal Research Institute of Northern Ohio

🇺🇸

Westlake, Ohio, United States

Central Sooner Research

🇺🇸

Norman, Oklahoma, United States

Frontier Clinical Re search, LLC

🇺🇸

Uniontown, Pennsylvania, United States

University Gastroenterology

🇺🇸

Providence, Rhode Island, United States

Gastro One

🇺🇸

Germantown, Tennessee, United States

Quality Medical Research

🇺🇸

Nashville, Tennessee, United States

Texas Clinical Research Institute, LLC

🇺🇸

Arlington, Texas, United States

Amel Med LLC

🇺🇸

Georgetown, Texas, United States

Cano Medical Center

🇺🇸

Harlingen, Texas, United States

TDDC dba GI Alliance Research

🇺🇸

Mansfield, Texas, United States

Gastroenterology Research of America, LLC

🇺🇸

San Antonio, Texas, United States

GI Alliance - Southlake

🇺🇸

Southlake, Texas, United States

Tyler Research Institute, LLC

🇺🇸

Tyler, Texas, United States

Tidewater Gastroenterology Pllc T/A Gastro. Assoc. of Tidewater

🇺🇸

Chesapeake, Virginia, United States

Emeritas Research Group

🇺🇸

Lansdowne Town Center, Virginia, United States

Gastroenterology Consultants and Endoscopy Center of Southwest Virginia

🇺🇸

Roanoke, Virginia, United States

AZ Sint Lucas (Sint Lucas)

🇧🇪

Gent, Belgium

South Edmonton Gastroenterology

🇨🇦

Edmonton, Alberta, Canada

Medwal

🇨🇱

Santiago, Chile

the First Hospital of Jilin University

🇨🇳

Changchun, China

Chongqing General Hospital

🇨🇳

Chongqing City, China

The second Affiliated Hospital of Guangzhou Medical University

🇨🇳

Guangzhou City, China

The sixth affiliated hospital of Sun Yat-Sen University

🇨🇳

Guangzhou City, China

Zhejiang Province Traditional Chinese Medical Hospital

🇨🇳

Hangzhou City, China

Sir Run Run Shaw Hospital Zhejiang University

🇨🇳

Hangzhou City, China

Anhui Provincial Hospital

🇨🇳

Hefei, China

Huizhou Central People's Hospital

🇨🇳

Huizhou, China

The 1st Affiliated Hospital of Nanchang Unversity

🇨🇳

Nanchang City, China

The First Affiliate Hospital of Guangxi Medical University

🇨🇳

Nanning, China

The First Affiliated Hospital of Ningbo University

🇨🇳

Ningbo City, China

Shanghai East Hospital

🇨🇳

Shanghai City, China

Peking University Shenzhen Hospital

🇨🇳

Shenzhen, China

Taizhou Hospital Of Zhejiang Province

🇨🇳

Taizhou City, China

The Central Hospital of Wuhan

🇨🇳

Wuhan City, China

Ren Min Hospital Affiliated Wu Han University

🇨🇳

Wuhan, China

Wuxi People's Hospital

🇨🇳

Wuxi, China

Zhongshan Hospital Xiamen University

🇨🇳

Xiamen, China

Zhuzhou Central Hospital

🇨🇳

Zhuzhou, China

CHU Nice - Hopital de l'Archet 2

🇫🇷

Nice, France

Boca Clinical Trials Mexico S.C. (Guadalajara)

🇲🇽

Guadalajara, Jalisco, Mexico

Medical Care & Research SA de CV

🇲🇽

Mérida, Yucatan, Mexico

Centrum Medyczne "Medis"

🇵🇱

Bydgoszcz, Poland

WIP Warsaw IBD Point Profesor Kierkus

🇵🇱

Warszawa, Poland

Vistamed & Vertigo Spó?Ka Z Ograniczon? Odpowiedzialno?Ci?

🇵🇱

Wroc?aw, Poland

Klinical Investigations Group LLC

🇵🇷

San Juan, Puerto Rico

Queen Anne Street Medical Centre

🇬🇧

London, United Kingdom

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