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

A Phase IIa, Randomised, Double-blind, Placebo-controlled Trial to Evaluate the Safety, Efficacy, Pharmacokinetics and Pharmacodynamics of BI 706321 Orally Administered for 12 Weeks in Patients With Crohn's Disease (CD) Receiving Ustekinumab Induction Treatment

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Crohn Disease
• Intervention / Treatment: Drug: Placebo; Drug: BI 706321; Drug: ustekinumab

• Study Type: Interventional
• Enrollment (Actual): 49
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Boehringer Ingelheim; Phone Number: 1-800-243-0127; Email: clintriage.rdg@boehringer-ingelheim.com

Study Locations

• Belgium
  • Bruxelles, Belgium, 1000
    • Brussels - UNIV St-Pierre
  • Gent, Belgium, 9000
    • AZ Maria Middelares
  • Gent, Belgium, 9000
    • AZ Sint-Lucas - Campus Sint Lucas
  • Leuven, Belgium, 3000
    • UZ Leuven
  • Liège, Belgium, 4000
    • Centre Hospitalier Universitaire de Liege
  • Mons, Belgium, 7000
    • UNIV Ambroise Paré
• Czechia
  • Hradec Kralove, Czechia, 50002
    • Hepato-Gastroenterologie HK, s.r.o.
  • Ostrava, Czechia, 708 52
    • University Hospital Ostrava
• Denmark
  • Køge, Denmark, 4600
    • Sjællands Universitetshospital, Køge
  • Odense C, Denmark, 5000
    • Odense University Hospital
  • Ålborg, Denmark, 9100
    • Aalborg Sygehus Syd
• Germany
  • Berlin, Germany, 12203
    • Charité - Universitätsmedizin Berlin
  • Berlin, Germany, 10117
    • Charité - Universitätsmedizin Berlin
  • Dresden, Germany, 01307
    • Universitatsklinikum Carl Gustav Carus Dresden
  • Kiel, Germany, 24105
    • Universitätsklinikum Schleswig-Holstein, Campus Kiel
  • Mannheim, Germany, 68167
    • Universitätsklinikum Mannheim GmbH
  • Ulm, Germany, 89081
    • Universitatsklinikum Ulm
• Hungary
  • Budapest, Hungary, 1033
    • Clinexpert Kft.
  • Budapest, Hungary, 1088
    • Semmelweis University
  • Debrecen, Hungary, 4032
    • University of Debrecen Clinical Centre
  • Gyongyos, Hungary, 3200
    • Bugat Pal Hospital, Gyongyos
• Italy
  • Catanzaro, Italy, 88100
    • Policlinico Universitario Mater Domini, Universita di Catanzaro
  • Milano, Italy, 20122
    • IRCCS Fondazione Ospedale Maggiore
  • Milano, Italy, 20132
    • IRCCS San Raffaele
  • Negrar (VR), Italy, 37024
    • Osp.Sacro Cuore-Don Calabria
  • Pavia, Italy, 27100
    • Fondazione IRCCS Policlinico S. Matteo
  • Roma, Italy, 00133
    • Az. Ospedaliera Universitaria Polic.Tor Vergata
  • San Donato Milanese (MI), Italy, 20097
    • IRCCS Policlinico San Donato
• Netherlands
  • Nijmegen, Netherlands, 6525 GA
    • Radboud Universitair Medisch Centrum
  • Tilburg, Netherlands, 5022 GC
    • St Elisabeth Ziekenhuis
• Poland
  • Bydgoszcz, Poland, 85231
    • NZOZ Medical Center KERmed
  • Knurow, Poland, 44-190
    • Indywidualna Specjalistyczna Praktyka Lekarska Maciej Zymla
  • Ksawerow, Poland, 95-054
    • Centrum Opieki Zdrowotnej Orkan-Med Stec-Michalska Sp. J.
  • Lublin, Poland, 20-582
    • Healthcare Center Gastromed - SCANMED GROUP
  • Szczecin, Poland, 71-434
    • Twoja Przychodnia-Szczecinskie Centrum Medyczne
  • Szczecin, Poland, 71- 685
    • Non-public Healthcare Center SONOMED
  • Warsaw, Poland, 02-507
    • National Medical Institute MSWiA
• Spain
  • Cordoba, Spain, 14004
    • payee-Hospital Universitario Reina Sofia. Cordoba
  • Madrid, Spain, 28006
    • Hospital La Princesa
  • Sabadell, Spain, 08208
    • CEIC Corporacio Sanitaria Parc Taulí
  • Sevilla, Spain, 41071
    • Hospital Virgen Macarena
  • Valencia, Spain, 46026
    • Hospital Politècnic La Fe
• United Kingdom
  • Liverpool, United Kingdom, L7 8XP
    • Royal Liverpool University Hospital
• United States
  • Arizona
    • Tucson, Arizona, United States, 85715
      • Del Sol Research Management, LLC
  • California
    • Northridge, California, United States, 91324
      • California Medical Research Associates Inc.
  • Connecticut
    • Hamden, Connecticut, United States, 06518
      • Medical Research Center of Connecticut, LLC
  • Florida
    • Hialeah, Florida, United States, 33016
      • Sweet Hope Research Specialty Inc
    • Inverness, Florida, United States, 34452
      • Nature Coast Clinical Research
    • Kissimmee, Florida, United States, 34741
      • I.H.S Health, LLC
    • Orlando, Florida, United States, 32825
      • Advanced Research Institute, Inc.
    • Saint Petersburg, Florida, United States, 33710
      • Himanshu Chandarana, MD, PA/Research Alliance
  • Georgia
    • Atlanta, Georgia, United States, 30310
      • Morehouse School of Medicine
    • Decatur, Georgia, United States, 30033
      • Atlanta Center For Gastroenterology, P.C.
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
    • Evanston, Illinois, United States, 60208
      • Northwestern University
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University
  • Michigan
    • Chesterfield, Michigan, United States, 48047
      • Clinical Research Inst of MI
    • Wyoming, Michigan, United States, 49519
      • Gastroenterology Associates of Western Michigan
  • Missouri
    • Liberty, Missouri, United States, 64068
      • BVL Clinical Research
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • New York
    • Middletown, New York, United States, 10940
      • Middletown Medical PC
  • North Carolina
    • Greenville, North Carolina, United States, 27834
      • Carolina Digestive Diseases
  • Texas
    • Houston, Texas, United States, 77030
      • Houston Methodist Hospital
    • Mansfield, Texas, United States, 76063
      • GI Alliance
    • San Antonio, Texas, United States, 78229
      • Southern Star Research Institute, LLC
    • Southlake, Texas, United States, 76092
      • GI Alliance
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • University of Utah Health Sciences Center
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • University of Virginia Health Science Center
  • Washington
    • Seattle, Washington, United States, 98195
      • University of Washington

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.
• Further inclusion criteria apply

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:

  • Any non-biologic medication for IBD (e.g.tacrolimus or mycophenolate mofetil, systemic corticosteroids), other than those allowed per inclusion criteria, within 30 days prior to randomisation
  • 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.
• Further exclusion criteria apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BI 706321 + ustekinumab	Drug: BI 706321; BI 706321; Drug: ustekinumab; ustekinumab
Placebo Comparator: Placebo + ustekinumab	Drug: Placebo; Placebo; Drug: ustekinumab; ustekinumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Absolute change from baseline in Simple Endoscopic Score for Crohn's disease (SES-CD) at week 12	SES-CD assesses the size of mucosal ulcers, the ulcerated surface, the endoscopic extension and the presence of stenosis. Each variable is scored from 0 to 3 for different parts of the intestine. A total score from 0 to 2 represents remission, 3 to 6 represents mild endoscopic activity, 7 to 15 represents moderate endoscopic activity and > 15 represents severe endoscopic activity.	At week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent change in Simple Endoscopic Score for Crohn's disease (SES-CD) from baseline at Week 12	SES-CD assesses the size of mucosal ulcers, the ulcerated surface, the endoscopic extension and the presence of stenosis. Each variable is scored from 0 to 3 for different parts of the intestine. A total score from 0 to 2 represents remission, 3 to 6 represents mild endoscopic activity, 7 to 15 represents moderate endoscopic activity and > 15 represents severe endoscopic activity.	At week 12
Endoscopic response	defined as > 50 percent (%) SES-CD reduction from baseline or for a induction baseline SES-CD of 4, at least a 2 point reduction from induction baseline	At week 12
Endoscopic response	defined as > 50 percent (%) SES-CD reduction from baseline or for a induction baseline SES-CD of 4, at least a 2 point reduction from induction baseline	At week 48
Endoscopic remission	defined as SES-CD score of ≤ 2	At week 12
Endoscopic remission	defined as SES-CD score of ≤ 2	At week 48
Biological remission	defined as C-Reactive Protein (CRP) < 5 milligrams/Litre (mg/L) and faecal calprotectin (FCP) < 250 micrograms/gram (ug/g)	At week 12
Biological remission	defined as C-Reactive Protein (CRP) < 5 milligrams/Litre (mg/L) and faecal calprotectin (FCP) < 250 micrograms/gram (ug/g)	At week 48
Clinical remission	defined as a Crohn's Disease Activity Index (CDAI) score of < 150 CDAI is comprised of eight variables which are summed after adjustment with a weighting factor. A CDAI score of ≤ 150 represents remission, 151 to 219 represents mild activity, 220 to 450 represents moderate activity and a score of > 450 represents severe or very severe activity.	At week 12
Clinical remission	defined as a Crohn's Disease Activity Index (CDAI) score of < 150	At week 48
Clinical response	defined by a CDAI reduction from baseline of at least 100 points, or a CDAI score of < 150	At week 12
Number of patients with treatment-emergent adverse event (TEAE) through end of treatment (EoT) and the REP period		Up to 104 days

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): October 4, 2021
• Primary Completion (Estimated): June 24, 2024
• Study Completion (Estimated): March 1, 2025

Study Registration Dates

• First Submitted: July 26, 2021
• First Submitted That Met QC Criteria: July 26, 2021
• First Posted (Actual): July 27, 2021

Study Record Updates

• Last Update Posted (Actual): April 16, 2024
• Last Update Submitted That Met QC Criteria: April 15, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Inflammatory Bowel Diseases; Crohn Disease; Dermatologic Agents; Ustekinumab
• Other Study ID Numbers: 1425-0003; 2020-004527-16 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

After the study is completed and the primary manuscript is accepted for publishing, researchers can use this following link https://www.mystudywindow.com/msw/datasharing to request access to the clinical study documents regarding this study, and upon a signed "Document Sharing Agreement".

Also, Researchers can use the following link https://www.mystudywindow.com/msw/datasharing to find information in order to request access to the clinical study data, for this and other listed studies, after the submission of a research proposal and according to the terms outlined in the website.

The data shared are the raw clinical study data sets.

• IPD Sharing 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.
• IPD Sharing 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'.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No