A Study to Test Whether BI 706321 Combined With Ustekinumab Helps People With Crohn's Disease

NCT ID: NCT04978493

Last Updated: 2025-09-04

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 49 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-12-02
• Study Completion Date: 2024-08-08

Brief Summary

This study is open to adults, aged 18-75 years, with moderate to severe Crohn's disease.

The purpose of this study is to find out whether BI 706321 combined with ustekinumab helps people with Crohn's disease. BI 706321 is a medicine being developed to treat Crohn's disease. Ustekinumab is a medicine already used to treat Crohn's disease.

Participants are put into 2 groups randomly, which means by chance. One group gets BI 706321 and ustekinumab. The other group gets placebo and ustekinumab.

Participants take BI 706321 or placebo as tablets every day. Placebo tablets look like BI 706321 tablets but do not contain any medicine. Ustekinumab is given as an infusion into a vein once at the beginning of the study. After that, ustekinumab is given as an injection under the skin every 2 months. Participants take BI 706321 or placebo in combination with ustekinumab for 3 months. After that, participants receive only ustekinumab for another 9 months.

Participants are in the study for about 1 year. During this time, they visit the study site about 13 times. At 3 of the visits, doctors do a colonoscopy to examine the bowel. The results from the colonoscopies are compared between the 2 groups. The doctors also regularly check participants' health and take note of any unwanted effects.

Conditions

Crohn Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

BI 706321 and ustekinumab

Participants with moderately to severely active Crohn's Disease (CD) administered one dose of 8 milligram (mg) BI 706321 as tablets orally once per day in the morning for 12 weeks in conjunction with standard induction dosing of ustekinumab, followed by ustekinumab maintenance dosing for an additional 36 weeks.

A single intravenous infusion of 260 mg ustekinumab (body weight ≤55 kilogram [kg]), 390 mg ustekinumab (body weight 55-85 kg), or 520 mg ustekinumab (body weight >85 kg) was administered on Day 0, followed by subcutaneous injection of 90 mg ustekinumab every 8 weeks.

Group Type: EXPERIMENTAL

BI 706321

Intervention Type: DRUG

One dose of 8 mg as tablets orally once per day in the morning

Ustekinumab

Intervention Type: DRUG

A single intravenous infusion of 260 mg (body weight ≤55 kg), 390 mg (body weight 55-85 kg), or 520 mg (body weight \>85 kg) was administered on Day 0, followed by subcutaneous injection of 90 mg every 8 weeks.

Placebo and ustekinumab

Participants with moderately to severely active CD administered one dose of placebo matching BI 706321 as tablets orally once per day in the morning for 12 weeks in conjunction with standard induction dosing of ustekinumab, followed by ustekinumab maintenance dosing for an additional 36 weeks.

A single intravenous infusion of 260 mg ustekinumab (body weight ≤55 kilogram [kg]), 390 mg ustekinumab (body weight 55-85 kg), or 520 mg ustekinumab (body weight >85 kg) was administered on Day 0, followed by subcutaneous injection of 90 mg ustekinumab every 8 weeks.

Group Type: PLACEBO_COMPARATOR

Ustekinumab

Intervention Type: DRUG

A single intravenous infusion of 260 mg (body weight ≤55 kg), 390 mg (body weight 55-85 kg), or 520 mg (body weight \>85 kg) was administered on Day 0, followed by subcutaneous injection of 90 mg every 8 weeks.

Placebo

Intervention Type: DRUG

One dose of placebo matching BI 706321 as tablets orally once per day in the morning

Interventions

BI 706321

One dose of 8 mg as tablets orally once per day in the morning

Intervention Type: DRUG

Ustekinumab

A single intravenous infusion of 260 mg (body weight ≤55 kg), 390 mg (body weight 55-85 kg), or 520 mg (body weight \>85 kg) was administered on Day 0, followed by subcutaneous injection of 90 mg every 8 weeks.

Intervention Type: DRUG

Placebo

One dose of placebo matching BI 706321 as tablets orally once per day in the morning

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Diagnosis of Crohn Disease (CD) for at least 3 months prior to visit 1, as confirmed at any time in the past by endoscopy and/OR, radiology, and supported by histology.
• Elevated C-reactive protein (≥ 5 mg/L) OR elevated fecal calprotectin (≥ 250 µg/g)
• Symptomatic CD defined as Crohn's Disease Activity Index (CDAI) ≥150.
• Presence of mucosal ulcers in at least one segment of the ileum or colon and a Simple Endoscopic Score for Crohn's disease (SES-CD) score ≥ 7 (for patients with isolated ileitis ≥4).
• Patients who are experienced at least 1 tumor necrosis factor (TNF) antagonists at a dose approved for CD. Patients may have stopped TNF antagonist treatment due to primary or secondary non-responsiveness, intolerance, or for other reasons.
• May be receiving a therapeutic dose of the following:

• Oral 5-aminosalicylic acid (5-ASA) compounds must have been at a stable dose for at least 4 weeks prior to randomisation and must continue on this dose until week 12 and/or
• Oral corticosteroids if indicated for treatment of CD must be at a prednisone equivalent dose of ≤ 20 mg/day, or ≤ 9 mg/day of budesonide, and have been at a stable dose for at least 2 weeks immediately prior to randomisation and must continue on this dose until week 12. and/or
• Azathioprine (AZA), mercaptopurine (MP), or methotrexate (MTX), provided that dose has been stable for the 8 weeks immediately prior to randomisation and must continue on this dose until week 12.
• Women of childbearing potential must be ready and able to use highly effective methods of birth control.

• Any biologic treatment with a TNF-alpha antagonist (adalimumab, infliximab, golimumab, certolizumab pegol) or vedolizumab (or a biosimilar of these drugs) within 4 weeks prior to randomisation. (If drug level testing for previously used biologic treatment confirms no detectable drug level before randomisation, patient can be enrolled despite not having completed 4 week from last treatment.)
• Any previous treatment with ustekinumab (or a biosimilar of this drug)
• Any previous treatment with an investigational (or subsequently approved) non-biologic/biologic drug for CD (including but not limited to JAK inhibitors [e.g. upadacitinib], S1P modulators, IL-23 inhibitors [e.g. risankizumab], antiintegrins).
• Any investigational drug for an indication other than CD during the course of the actual study and within 30 days or 5 half-lives (whichever is longer) prior to randomisation.
• Any prior exposure to rituximab within 1 year prior to randomisation.
• Positive stool examination for C difficile or other intestinal pathogens <30 days prior to randomization
• Evidence of colonic moderate/severe mucosal dysplasia or colonic adenomas, unless properly removed
• Increased risk of infectious complications (e.g. recent pyogenic infection, any congenital or acquired immunodeficiency (e.g. human immunodeficiency virus (HIV)), past organ or stem cell transplantation (with exception of a corneal transplant > 12 weeks prior to screening) or have ever received stem cell therapy (e.g., Prochymal). Prior treatment with a somatic cell therapy product (e.g., Alofisel) is not excluded, provided it was administered > 8 weeks prior to randomisation.
• Live or attenuated vaccination within 4 weeks prior to randomisation.
• Presence of clinically significant acute or chronic infections not otherwise listed, including viral hepatitis, COVID-19, or others based on investigator's judgement.
• A marked baseline prolongation of QT/QTc interval (such as QTcF intervals that are greater than 450 ms for men, 470 ms for female) or any other relevant electrocardiogram (ECG) finding at screening. Both have to be confirmed by repeated ECG recording.

Exclusion Criteria

• Have any current or prior abscesses, unless they have been drained and treated at least 6 weeks prior to randomisation and are not anticipated to require surgery. Patients with active fistulas may be included if there is no anticipation of a need for surgery and there are currently no abscesses present based on investigator's judgement.
• Have complications of CD such as strictures, stenosis, short bowel syndrome, or any other manifestation that might require surgery, or could preclude the use of SES-CD/CDAI to assess response to therapy, or would possibly confound the evaluation of benefit from treatment with BI 706321 (based on investigator's judgement).
• Patient with an inflammatory bowel disease (IBD) diagnosis other than CD.
• Have had any kind of bowel resection or diversion within 4 months or any other intra-abdominal surgery within 3 months prior to visit 1. Patients with current ileostomy, colostomy, or ileorectal anastomosis are excluded.
• Treatment with:

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Boehringer Ingelheim

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

California Medical Research Associates Inc.

Northridge, California, United States

Sweet Hope Research Specialty Inc

Hialeah, Florida, United States

Nature Coast Clinical Research

Inverness, Florida, United States

I.H.S Health, LLC

Kissimmee, Florida, United States

Advanced Research Institute, Inc.

Orlando, Florida, United States

Rush University Medical Center

Chicago, Illinois, United States

Indiana University

Indianapolis, Indiana, United States

Gastroenterology Associates of Western Michigan

Wyoming, Michigan, United States

BVL Clinical Research

Liberty, Missouri, United States

Carolina Digestive Diseases

Greenville, North Carolina, United States

Houston Methodist Hospital

Houston, Texas, United States

Southern Star Research Institute, LLC

San Antonio, Texas, United States

GI Alliance

Southlake, Texas, United States

University of Utah Health Sciences Center

Salt Lake City, Utah, United States

University of Washington

Seattle, Washington, United States

Brussels - UNIV St-Pierre

Brussels, , Belgium

AZ Maria Middelares

Ghent, , Belgium

AZ Sint-Lucas - Campus Sint Lucas

Ghent, , Belgium

UZ Leuven

Leuven, , Belgium

Centre Hospitalier Universitaire de Liège

Liège, , Belgium

UNIV Ambroise Paré

Mons, , Belgium

Hepato-Gastroenterologie HK, s.r.o.

Hradec Králové, , Czechia

University Hospital Ostrava

Ostrava, , Czechia

Aalborg Sygehus Syd

Aalborg, , Denmark

Universitätsklinikum Ulm

Ulm, , Germany

Clinexpert Kft.

Budapest, , Hungary

University of Debrecen Clinical Centre

Debrecen, , Hungary

Bugat Pal Hospital, Gyongyos

Gyöngyös, , Hungary

Policlinico Universitario Mater Domini, Universita di Catanzaro

Catanzaro, , Italy

IRCCS Fondazione Ospedale Maggiore

Milan, , Italy

IRCCS San Raffaele

Milan, , Italy

Osp.Sacro Cuore-Don Calabria

Negrar (VR), , Italy

Fondazione IRCCS Policlinico S. Matteo

Pavia, , Italy

Az. Ospedaliera Universitaria Polic.Tor Vergata

Roma, , Italy

IRCCS Policlinico San Donato

San Donato Milanese (MI), , Italy

Radboud Universitair Medisch Centrum

Nijmegen, , Netherlands

St Elisabeth Ziekenhuis

Tilburg, , Netherlands

NZOZ Medical Center KERmed

Bydgoszcz, , Poland

Indywidualna Specjalistyczna Praktyka Lekarska Maciej Zymla

Knurów, , Poland

Centrum Opieki Zdrowotnej Orkan-Med Stec-Michalska sp. j.

Ksawerów, , Poland

Healthcare Center Gastromed - SCANMED GROUP

Lublin, , Poland

Twoja Przychodnia-Szczecinskie Centrum Medyczne

Szczecin, , Poland

National Medical Institute MSWiA

Warsaw, , Poland

payee-Hospital Universitario Reina Sofia. Cordoba

Córdoba, , Spain

Hospital La Princesa

Madrid, , Spain

CEIC Corporacio Sanitaria Parc Taulí

Sabadell, , Spain

Hospital Virgen Macarena

Seville, , Spain

Hospital Politècnic La Fe

Valencia, , Spain

Royal Liverpool University Hospital

Liverpool, , United Kingdom

Countries

United States; Belgium; Czechia; Denmark; Germany; Hungary; Italy; Netherlands; Poland; Spain; United Kingdom

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

http://www.mystudywindow.com

Related Info

Other Identifiers

2020-004527-16

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

1425-0003

Identifier Type: -

Identifier Source: org_study_id