A Study to Test Whether BI 706321 Combined With Ustekinumab Helps People With Crohn's Disease
- Registration Number
- NCT04978493
- Lead Sponsor
- Boehringer Ingelheim
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 49
-
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
-
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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description BI 706321 + ustekinumab BI 706321 - BI 706321 + ustekinumab ustekinumab - Placebo + ustekinumab ustekinumab - Placebo + ustekinumab Placebo -
- Primary Outcome Measures
Name Time Method Absolute change from baseline in Simple Endoscopic Score for Crohn's disease (SES-CD) at week 12 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.
- Secondary Outcome Measures
Name Time Method Clinical response At week 12 defined by a CDAI reduction from baseline of at least 100 points, or a CDAI score of \< 150
Number of patients with treatment-emergent adverse event (TEAE) through end of treatment (EoT) and the REP period Up to 104 days Percent change in Simple Endoscopic Score for Crohn's disease (SES-CD) from baseline at Week 12 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.
Endoscopic remission At week 48 defined as SES-CD score of ≤ 2
Endoscopic response At week 48 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
Biological remission At week 48 defined as C-Reactive Protein (CRP) \< 5 milligrams/Litre (mg/L) and faecal calprotectin (FCP) \< 250 micrograms/gram (ug/g)
Clinical remission At week 48 defined as a Crohn's Disease Activity Index (CDAI) score of \< 150
Trial Locations
- Locations (49)
Indiana University
🇺🇸Indianapolis, Indiana, United States
Southern Star Research Institute, LLC
🇺🇸San Antonio, Texas, United States
University of Utah Health Sciences Center
🇺🇸Salt Lake City, Utah, United States
Twoja Przychodnia-Szczecinskie Centrum Medyczne
🇵🇱Szczecin, Poland
Rush University Medical Center
🇺🇸Chicago, Illinois, United States
Sweet Hope Research Specialty Inc
🇺🇸Hialeah, Florida, United States
California Medical Research Associates Inc.
🇺🇸Northridge, California, United States
Nature Coast Clinical Research
🇺🇸Inverness, Florida, United States
I.H.S Health, LLC
🇺🇸Kissimmee, Florida, United States
Houston Methodist Hospital
🇺🇸Houston, Texas, United States
BVL Clinical Research
🇺🇸Liberty, Missouri, United States
Gastroenterology Associates of Western Michigan
🇺🇸Wyoming, Michigan, United States
Carolina Digestive Diseases
🇺🇸Greenville, North Carolina, United States
GI Alliance
🇺🇸Southlake, Texas, United States
University of Washington
🇺🇸Seattle, Washington, United States
Brussels - UNIV St-Pierre
🇧🇪Bruxelles, Belgium
AZ Maria Middelares
🇧🇪Gent, Belgium
AZ Sint-Lucas - Campus Sint Lucas
🇧🇪Gent, Belgium
UZ Leuven
🇧🇪Leuven, Belgium
Centre Hospitalier Universitaire de Liège
🇧🇪Liège, Belgium
UNIV Ambroise Paré
🇧🇪Mons, Belgium
Hepato-Gastroenterologie HK, s.r.o.
🇨🇿Hradec Kralove, Czechia
Clinexpert Kft.
🇭🇺Budapest, Hungary
University of Debrecen Clinical Centre
🇭🇺Debrecen, Hungary
Bugat Pal Hospital, Gyongyos
🇭🇺Gyongyos, Hungary
University Hospital Ostrava
🇨🇿Ostrava, Czechia
Aalborg Sygehus Syd
🇩🇰Ålborg, Denmark
Universitätsklinikum Ulm
🇩🇪Ulm, Germany
Policlinico Universitario Mater Domini, Universita di Catanzaro
🇮🇹Catanzaro, Italy
IRCCS Fondazione Ospedale Maggiore
🇮🇹Milano, Italy
IRCCS San Raffaele
🇮🇹Milano, Italy
Az. Ospedaliera Universitaria Polic.Tor Vergata
🇮🇹Roma, Italy
Osp.Sacro Cuore-Don Calabria
🇮🇹Negrar (VR), Italy
Fondazione IRCCS Policlinico S. Matteo
🇮🇹Pavia, 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
Hospital Politècnic La Fe
🇪🇸Valencia, Spain
Indywidualna Specjalistyczna Praktyka Lekarska Maciej Zymla
🇵🇱Knurow, Poland
Centrum Opieki Zdrowotnej Orkan-Med Stec-Michalska sp. j.
🇵🇱Ksawerow, Poland
National Medical Institute MSWiA
🇵🇱Warsaw, Poland
payee-Hospital Universitario Reina Sofia. Cordoba
🇪🇸Cordoba, Spain
Hospital La Princesa
🇪🇸Madrid, Spain
Healthcare Center Gastromed - SCANMED GROUP
🇵🇱Lublin, Poland
CEIC Corporacio Sanitaria Parc Taulí
🇪🇸Sabadell, Spain
Hospital Virgen Macarena
🇪🇸Sevilla, Spain
Advanced Research Institute, Inc.
🇺🇸Orlando, Florida, United States
Royal Liverpool University Hospital
🇬🇧Liverpool, United Kingdom