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

NCT04978493 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: 1425-00032020-004527-16
• Study Type: interventional
• Target: 49
• Locations: 11 countries
• Sites: 49

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

Outcome Measures

Primary Outcomes (1)

• Absolute Change From Baseline in Simple Endoscopic Score for Crohn's Disease (SES-CD) at Week 12

  Absolute change from baseline in Simple Endoscopic Score for Crohn's disease (SES-CD) at Week 12 is reported. The SES-CD is a numerical grading system composed of 4 variables (presence of ulcers, ulcerated surface, affected surface, presence of narrowings) recorded sequentially in 5 segments: rectum, left colon, transverse colon, right colon, ileum. Each variable is assigned a value from 0 to 3, and the total score, ranging from 0 to 56, is obtained by adding each variable. Higher values indicate worse endoscopic inflammation. To achieve a score of 56, the maximum score for the "presence of narrowings" variable has to be be 2 (not 3) for the four segments leading up to the ileum. The analysis was a restricted maximum likelihood (REML) based analysis of covariance (ANCOVA). For the ANCOVA model, absolute change in SES-CD score was the dependent variable, treatment group and baseline corticosteroid use (yes/no) were fixed effects and baseline SES-CD score was a continuous covariate.

  Within 28 days before randomization (baseline) and 12 weeks after first drug administration.

Secondary Outcomes (11)

• Percent Change in SES-CD From Baseline at Week 12

  Within 28 days before randomization (baseline) and 12 weeks after first drug administration.

• Percentage of Patients With Endoscopic Response (Defined as >50% SES-CD Reduction From Baseline, or for an Induction Baseline SES-CD of 4, at Least a 2 Point Reduction From Induction Baseline) at Week 12

  Within 28 days before randomization (baseline) and 12 weeks after first drug administration.

• Percentage of Patients With Endoscopic Response (Defined as >50% SES-CD Reduction From Baseline, or for an Induction Baseline SES-CD of 4, at Least a 2 Point Reduction From Induction Baseline) at Week 48

  Within 28 days before randomization (baseline) and 48 weeks after first drug administration.

• Percentage of Patients With Endoscopic Remission (Defined as SES-CD Score of ≤2) at Week 12

  12 weeks after first drug administration.

• Percentage of Patients With Endoscopic Remission (Defined as SES-CD Score of ≤2) at Week 48

  48 weeks after first drug administration.

Study Arms (2)

BI 706321 and ustekinumab

EXPERIMENTAL

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.

Drug: BI 706321; Drug: Ustekinumab

Placebo and ustekinumab

PLACEBO COMPARATOR

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.

Drug: Ustekinumab; Drug: Placebo

Interventions

BI 706321 DRUG

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

BI 706321 and ustekinumab

Ustekinumab 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.

BI 706321 and ustekinumab; Placebo and ustekinumab

Placebo DRUG

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

Placebo and ustekinumab

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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:
• 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.

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (49)

California Medical Research Associates Inc.

Northridge, California, 91324, United States

Location

Sweet Hope Research Specialty Inc

Hialeah, Florida, 33016, United States

Location

Nature Coast Clinical Research

Inverness, Florida, 34452, United States

Location

I.H.S Health, LLC

Kissimmee, Florida, 34741, United States

Location

Advanced Research Institute, Inc.

Orlando, Florida, 32825, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

Indiana University

Indianapolis, Indiana, 46202, United States

Location

Gastroenterology Associates of Western Michigan

Wyoming, Michigan, 49519, United States

Location

BVL Clinical Research

Liberty, Missouri, 64068, United States

Location

Carolina Digestive Diseases

Greenville, North Carolina, 27834, United States

Location

Houston Methodist Hospital

Houston, Texas, 77030, United States

Location

Southern Star Research Institute, LLC

San Antonio, Texas, 78229, United States

Location

GI Alliance

Southlake, Texas, 76092, United States

Location

University of Utah Health Sciences Center

Salt Lake City, Utah, 84132, United States

Location

University of Washington

Seattle, Washington, 98195, United States

Location

Brussels - UNIV St-Pierre

Brussels, 1000, Belgium

Location

AZ Maria Middelares

Ghent, 9000, Belgium

Location

AZ Sint-Lucas - Campus Sint Lucas

Ghent, 9000, Belgium

Location

UZ Leuven

Leuven, 3000, Belgium

Location

Centre Hospitalier Universitaire de Liège

Liège, 4000, Belgium

Location

UNIV Ambroise Paré

Mons, 7000, Belgium

Location

Hepato-Gastroenterologie HK, s.r.o.

Hradec Králové, 50002, Czechia

Location

University Hospital Ostrava

Ostrava, 708 52, Czechia

Location

Aalborg Sygehus Syd

Aalborg, 9100, Denmark

Location

Universitätsklinikum Ulm

Ulm, 89081, Germany

Location

Clinexpert Kft.

Budapest, 1033, Hungary

Location

University of Debrecen Clinical Centre

Debrecen, 4032, Hungary

Location

Bugat Pal Hospital, Gyongyos

Gyöngyös, 3200, Hungary

Location

Policlinico Universitario Mater Domini, Universita di Catanzaro

Catanzaro, 88100, Italy

Location

IRCCS Fondazione Ospedale Maggiore

Milan, 20122, Italy

Location

IRCCS San Raffaele

Milan, 20132, Italy

Location

Osp.Sacro Cuore-Don Calabria

Negrar (VR), 37024, Italy

Location

Fondazione IRCCS Policlinico S. Matteo

Pavia, 27100, Italy

Location

Az. Ospedaliera Universitaria Polic.Tor Vergata

Roma, 00133, Italy

Location

IRCCS Policlinico San Donato

San Donato Milanese (MI), 20097, Italy

Location

Radboud Universitair Medisch Centrum

Nijmegen, 6525 GA, Netherlands

Location

St Elisabeth Ziekenhuis

Tilburg, 5022 GC, Netherlands

Location

NZOZ Medical Center KERmed

Bydgoszcz, 85231, Poland

Location

Indywidualna Specjalistyczna Praktyka Lekarska Maciej Zymla

Knurów, 44-190, Poland

Location

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

Ksawerów, 95-054, Poland

Location

Healthcare Center Gastromed - SCANMED GROUP

Lublin, 20-582, Poland

Location

Twoja Przychodnia-Szczecinskie Centrum Medyczne

Szczecin, 71-434, Poland

Location

National Medical Institute MSWiA

Warsaw, 02-507, Poland

Location

payee-Hospital Universitario Reina Sofia. Cordoba

Córdoba, 14004, Spain

Location

Hospital La Princesa

Madrid, 28006, Spain

Location

CEIC Corporacio Sanitaria Parc Taulí

Sabadell, 08208, Spain

Location

Hospital Virgen Macarena

Seville, 41071, Spain

Location

Hospital Politècnic La Fe

Valencia, 46026, Spain

Location

Royal Liverpool University Hospital

Liverpool, L7 8XP, United Kingdom

Location

Related Links

• Related Info

MeSH Terms

Conditions

Crohn Disease

Interventions

Ustekinumab

Condition Hierarchy (Ancestors)

Inflammatory Bowel Diseases; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

Due to trial discontinuation, patients that were ongoing in the follow-up period could not receive ustekinumab for the full 36 weeks, so End of Study assessments were either performed earlier or were missing, as was the case for endoscopies. Consequently, more patients had missing 48-week data that necessitated imputation via Non-response imputation or Last observation carried forward than there would have been had the trial continued as planned, so 48-week data must be interpreted with caution.

Results Point of Contact

• Title: Boehringer Ingelheim, Call Center
• Organization: Boehringer Ingelheim

clintriage.rdg@boehringer-ingelheim.com

1-800-243-0127

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Ustekinumab treatment is open-label for the Sponsor, patients and investigator/site staff.

Study Record Dates

• First Submitted: July 26, 2021
• First Posted: July 27, 2021
• Study Start: December 2, 2021
• Primary Completion: July 8, 2024
• Study Completion: August 8, 2024
• Last Updated: September 4, 2025
• Results First Posted: September 4, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: After all regulatory activities are completed in the US and EU for the product and indication, and after the primary manuscript has been accepted for publication.
• Access Criteria: For study documents - upon signing of a 'Document Sharing Agreement'. For study data - 1. after the submission and approval of the research proposal (checks will be performed by both the independent review panel and the sponsor, including checking that the planned analysis does not compete with sponsor's publication plan); 2. and upon signing of a 'Data Sharing Agreement'.

Locations

PL (6); BE (6); US (15); DK (1); HU (3); IT (7); CZ (2); ES (5); GB (1); DE (1); NL (2)