Clinical trial NCT04978493: A Study to Test Whether BI 706321 Combined With Ustekinumab Helps People With Crohn's Disease
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Crohn Disease
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2021-07-27
Enrollment: 49
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Ustekinumab treatment is open-label for the Sponsor, patients and investigator/site staff.
Primary purpose: TREATMENT

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.


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.
* 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

Primary outcomes:
measure: Absolute change from baseline in Simple Endoscopic Score for Crohn's disease (SES-CD) at week 12
timeFrame: At week 12
Secondary outcomes:
measure: Percent change in Simple Endoscopic Score for Crohn's disease (SES-CD) from baseline at Week 12
timeFrame: At week 12
measure: Endoscopic response
timeFrame: At week 12
measure: Endoscopic response
timeFrame: At week 48
measure: Endoscopic remission
timeFrame: At week 12
measure: Endoscopic remission
timeFrame: At week 48
measure: Biological remission
timeFrame: At week 12
measure: Biological remission
timeFrame: At week 48
measure: Clinical remission
timeFrame: At week 12
measure: Clinical remission
timeFrame: At week 48
measure: Clinical response
timeFrame: At week 12
measure: Number of patients with treatment-emergent adverse event (TEAE) through end of treatment (EoT) and the REP period
timeFrame: Up to 104 days
Other outcomes:
Locations:
city: Northridge
country: United States
facility: California Medical Research Associates Inc.
state: California
city: Hialeah
country: United States
facility: Sweet Hope Research Specialty Inc
state: Florida
city: Inverness
country: United States
facility: Nature Coast Clinical Research
state: Florida
city: Kissimmee
country: United States
facility: I.H.S Health, LLC
state: Florida
city: Orlando
country: United States
facility: Advanced Research Institute, Inc.
state: Florida
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Wyoming
country: United States
facility: Gastroenterology Associates of Western Michigan
state: Michigan
city: Liberty
country: United States
facility: BVL Clinical Research
state: Missouri
city: Greenville
country: United States
facility: Carolina Digestive Diseases
state: North Carolina
city: Houston
country: United States
facility: Houston Methodist Hospital
state: Texas
city: San Antonio
country: United States
facility: Southern Star Research Institute, LLC
state: Texas
city: Southlake
country: United States
facility: GI Alliance
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah Health Sciences Center
state: Utah
city: Seattle
country: United States
facility: University of Washington
state: Washington
city: Bruxelles
country: Belgium
facility: Brussels - UNIV St-Pierre
city: Gent
country: Belgium
facility: AZ Maria Middelares
city: Gent
country: Belgium
facility: AZ Sint-Lucas - Campus Sint Lucas
city: Leuven
country: Belgium
facility: UZ Leuven
city: Liège
country: Belgium
facility: Centre Hospitalier Universitaire de Liège
city: Mons
country: Belgium
facility: UNIV Ambroise Paré
city: Hradec Kralove
country: Czechia
facility: Hepato-Gastroenterologie HK, s.r.o.
city: Ostrava
country: Czechia
facility: University Hospital Ostrava
city: Ålborg
country: Denmark
facility: Aalborg Sygehus Syd
city: Ulm
country: Germany
facility: Universitätsklinikum Ulm
city: Budapest
country: Hungary
facility: Clinexpert Kft.
city: Debrecen
country: Hungary
facility: University of Debrecen Clinical Centre
city: Gyongyos
country: Hungary
facility: Bugat Pal Hospital, Gyongyos
city: Catanzaro
country: Italy
facility: Policlinico Universitario Mater Domini, Universita di Catanzaro
city: Milano
country: Italy
facility: IRCCS Fondazione Ospedale Maggiore
city: Milano
country: Italy
facility: IRCCS San Raffaele
city: Negrar (VR)
country: Italy
facility: Osp.Sacro Cuore-Don Calabria
city: Pavia
country: Italy
facility: Fondazione IRCCS Policlinico S. Matteo
city: Roma
country: Italy
facility: Az. Ospedaliera Universitaria Polic.Tor Vergata
city: San Donato Milanese (MI)
country: Italy
facility: IRCCS Policlinico San Donato
city: Nijmegen
country: Netherlands
facility: Radboud Universitair Medisch Centrum
city: Tilburg
country: Netherlands
facility: St Elisabeth Ziekenhuis
city: Bydgoszcz
country: Poland
facility: NZOZ Medical Center KERmed
city: Knurow
country: Poland
facility: Indywidualna Specjalistyczna Praktyka Lekarska Maciej Zymla
city: Ksawerow
country: Poland
facility: Centrum Opieki Zdrowotnej Orkan-Med Stec-Michalska sp. j.
city: Lublin
country: Poland
facility: Healthcare Center Gastromed - SCANMED GROUP
city: Szczecin
country: Poland
facility: Twoja Przychodnia-Szczecinskie Centrum Medyczne
city: Warsaw
country: Poland
facility: National Medical Institute MSWiA
city: Cordoba
country: Spain
facility: payee-Hospital Universitario Reina Sofia. Cordoba
city: Madrid
country: Spain
facility: Hospital La Princesa
city: Sabadell
country: Spain
facility: CEIC Corporacio Sanitaria Parc Taulí
city: Sevilla
country: Spain
facility: Hospital Virgen Macarena
city: Valencia
country: Spain
facility: Hospital Politècnic La Fe
city: Liverpool
country: United Kingdom
facility: Royal Liverpool University Hospital
Study officials:
References: