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

Crohn Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04978493
• Other study ID #: 1425-0003
• Secondary ID: 2020-004527-16
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: October 4, 2021
• Est. completion date: March 1, 2025

Study information

• Verified date: April 2024
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 49
• Est. completion date: March 1, 2025
• Est. primary completion date: July 10, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Crohn Disease

Intervention

Drug:
• BI 706321
BI 706321
• ustekinumab
ustekinumab
• Placebo
Placebo

Locations

Country	Name	City	State
Belgium	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
Czechia	Hepato-Gastroenterologie HK, s.r.o.	Hradec Kralove
Czechia	University Hospital Ostrava	Ostrava
Denmark	Aalborg Sygehus Syd	Ålborg
Denmark	Sjællands Universitetshospital, Køge	Køge
Denmark	Odense University Hospital	Odense C
Germany	Charité - Universitätsmedizin Berlin	Berlin
Germany	Charité - Universitätsmedizin Berlin	Berlin
Germany	Universitätsklinikum Carl Gustav Carus Dresden	Dresden
Germany	Universitätsklinikum Schleswig-Holstein, Campus Kiel	Kiel
Germany	Universitätsklinikum Mannheim GmbH	Mannheim
Germany	Universitätsklinikum Ulm	Ulm
Hungary	Clinexpert Kft.	Budapest
Hungary	Semmelweis University	Budapest
Hungary	University of Debrecen Clinical Centre	Debrecen
Hungary	Bugat Pal Hospital, Gyongyos	Gyongyos
Italy	Policlinico Universitario Mater Domini, Universita di Catanzaro	Catanzaro
Italy	IRCCS Fondazione Ospedale Maggiore	Milano
Italy	IRCCS San Raffaele	Milano
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)
Netherlands	Radboud Universitair Medisch Centrum	Nijmegen
Netherlands	St Elisabeth Ziekenhuis	Tilburg
Poland	NZOZ Medical Center KERmed	Bydgoszcz
Poland	Indywidualna Specjalistyczna Praktyka Lekarska Maciej Zymla	Knurow
Poland	Centrum Opieki Zdrowotnej Orkan-Med Stec-Michalska sp. j.	Ksawerow
Poland	Healthcare Center Gastromed - SCANMED GROUP	Lublin
Poland	Non-public Healthcare Center SONOMED	Szczecin
Poland	Twoja Przychodnia-Szczecinskie Centrum Medyczne	Szczecin
Poland	National Medical Institute MSWiA	Warsaw
Spain	payee-Hospital Universitario Reina Sofia. Cordoba	Cordoba
Spain	Hospital La Princesa	Madrid
Spain	CEIC Corporacio Sanitaria Parc Taulí	Sabadell
Spain	Hospital Virgen Macarena	Sevilla
Spain	Hospital Politècnic La Fe	Valencia
United Kingdom	Royal Liverpool University Hospital	Liverpool
United States	Morehouse School of Medicine	Atlanta	Georgia
United States	University of Virginia Health Science Center	Charlottesville	Virginia
United States	Clinical Research Inst of MI	Chesterfield	Michigan
United States	Rush University Medical Center	Chicago	Illinois
United States	Atlanta Center for Gastroenterology, P.C.	Decatur	Georgia
United States	Northwestern University	Evanston	Illinois
United States	Carolina Digestive Diseases	Greenville	North Carolina
United States	Medical Research Center of Connecticut, LLC	Hamden	Connecticut
United States	Sweet Hope Research Specialty Inc	Hialeah	Florida
United States	Houston Methodist Hospital	Houston	Texas
United States	Indiana University	Indianapolis	Indiana
United States	Nature Coast Clinical Research	Inverness	Florida
United States	I.H.S Health, LLC	Kissimmee	Florida
United States	BVL Clinical Research	Liberty	Missouri
United States	GI Alliance	Mansfield	Texas
United States	Middletown Medical PC	Middletown	New York
United States	California Medical Research Associates Inc.	Northridge	California
United States	Advanced Research Institute, Inc.	Orlando	Florida
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Himanshu Chandarana, MD, PA/Research Alliance	Saint Petersburg	Florida
United States	University of Utah Health Sciences Center	Salt Lake City	Utah
United States	Southern Star Research Institute, LLC	San Antonio	Texas
United States	University of Washington	Seattle	Washington
United States	GI Alliance	Southlake	Texas
United States	Del Sol Research Management, LLC	Tucson	Arizona
United States	Gastroenterology Associates of Western Michigan	Wyoming	Michigan

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	Endoscopic remission	defined as SES-CD score of = 2	At week 12
Secondary	Endoscopic remission	defined as SES-CD score of = 2	At week 48
Secondary	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
Secondary	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
Secondary	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
Secondary	Clinical remission	defined as a Crohn's Disease Activity Index (CDAI) score of < 150	At week 48
Secondary	Clinical response	defined by a CDAI reduction from baseline of at least 100 points, or a CDAI score of < 150	At week 12
Secondary	Number of patients with treatment-emergent adverse event (TEAE) through end of treatment (EoT) and the REP period		Up to 104 days

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