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

• Sponsor: Boehringer Ingelheim (Industry)
• Overall Status: Recruiting
• CT.gov ID: NCT04978493
• Collaborator: (none)
• Enrollment: 50
• Locations: 35
• Arms: 2
• Anticipated Duration (Months): 28.8
• Patients Per Site: 1.4
• Patients Per Site Per Month: 0

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Crohn Disease	Drug: BI 706321; Drug: ustekinumab; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 50 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Ustekinumab treatment is open-label for the Sponsor, patients and investigator/site staff.Ustekinumab treatment is open-label for the Sponsor, patients and investigator/site staff.
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Oct 4, 2021
• Anticipated Primary Completion Date: Jun 23, 2023
• Anticipated Study Completion Date: Feb 29, 2024

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. 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

1. 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.

2. Endoscopic response [At week 12]

   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

3. 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

4. Endoscopic remission [At week 12]

   defined as SES-CD score of ≤ 2

5. Endoscopic remission [At week 48]

   defined as SES-CD score of ≤ 2

6. Biological remission [At week 12]

   defined as C-Reactive Protein (CRP) < 5 milligrams/Litre (mg/L) and faecal calprotectin (FCP) < 250 micrograms/gram (ug/g)

7. 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)

8. Clinical remission [At week 12]

   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.

9. Clinical remission [At week 48]

   defined as a Crohn's Disease Activity Index (CDAI) score of < 150

10. Clinical response [At week 12]

    defined by a CDAI reduction from baseline of at least 100 points, or a CDAI score of < 150

11. Number of patients with treatment-emergent adverse event (TEAE) through end of treatment (EoT) and the REP period [Up to 104 days]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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 within 4 weeks prior to randomisation.

• Any previous treatment with ustekinumab

• Any previous treatment with an investigational non[1]biologic or biologic drug for CD (including but not limited to JAK inhibitors, S1P modulators, interleukin (IL)-23 inhibitors, anti-integrins).

• 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	California Medical Research Associates Inc.	Northridge	California	United States	91324
2	Medical Research Center of Connecticut, LLC	Hamden	Connecticut	United States	06518
3	Sweet Hope Research Specialty Inc	Hialeah	Florida	United States	33016
4	Nature Coast Clinical Research	Inverness	Florida	United States	34452
5	I.H.S Health, LLC	Kissimmee	Florida	United States	34741
6	Atlanta Center for Gastroenterology, P.C.	Decatur	Georgia	United States	30033
7	Rush University Medical Center	Chicago	Illinois	United States	60612
8	Indiana University	Indianapolis	Indiana	United States	46202
9	Clinical Research Inst of MI	Chesterfield	Michigan	United States	48047
10	Gastroenterology Associates of Western Michigan	Wyoming	Michigan	United States	49519
11	BVL Clinical Research	Liberty	Missouri	United States	64068
12	AGA Clinical Research Associates, LLC	Egg Harbor Township	New Jersey	United States	08234
13	Carolina Digestive Diseases	Greenville	North Carolina	United States	27834
14	Southern Star Research Institute, LLC	San Antonio	Texas	United States	78229
15	University of Utah Health Sciences Center	Salt Lake City	Utah	United States	84132
16	Clinical Research & Consulting Center, LLC	Fairfax	Virginia	United States	22031
17	Brussels - UNIV St-Pierre	Bruxelles		Belgium	1000
18	AZ Maria Middelares	Gent		Belgium	9000
19	AZ Sint-Lucas - Campus Sint Lucas	Gent		Belgium	9000
20	UZ Leuven	Leuven		Belgium	3000
21	Centre Hospitalier Universitaire de Liège	Liège		Belgium	4000
22	Fakultni nemocnice u sv. Anny v Brne	Brno		Czechia	65691
23	University Hospital Ostrava	Ostrava		Czechia	708 52
24	Policlinico Universitario Mater Domini, Universita di Catanzaro	Catanzaro		Italy	88100
25	IRCCS Fondazione Ospedale Maggiore	Milano		Italy	20122
26	Osp.Sacro Cuore-Don Calabria	Negrar (VR)		Italy	37024
27	Ospedale di Circolo	Rho (mi)		Italy	20017
28	NZOZ Medical Center KERmed	Bydgoszcz		Poland	85231
29	Indywidualna Specjalistyczna Praktyka Lekarska Maciej Zymla	Knurow		Poland	44-190
30	Medical Center Plejady	Krakow		Poland	30-363
31	Centrum Opieki Zdrowotnej Orkan-Med Stec-Michalska sp. j.	Ksawerow		Poland	95-054
32	Twoja Przychodnia-Szczecinskie Centrum Medyczne	Szczecin		Poland	71-434
33	Central Clinical Hospital MSWiA, Internal Diseases, Warsaw	Warsaw		Poland	02-507
34	Non-Public Outpatient Medical Care VIVAMED, Warsaw	Warsaw		Poland	03-580
35	ETG Zamosc	Zamosc		Poland	22400

Sponsors and Collaborators

• Boehringer Ingelheim

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Related Info

Publications

None provided.

• Responsible Party: Boehringer Ingelheim
• ClinicalTrials.gov Identifier: NCT04978493
• Other Study ID Numbers: 1425-0003; 2020-004527-16
• First Posted: Jul 27, 2021
• Last Update Posted: Aug 22, 2022
• Last Verified: Aug 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Crohn Disease; Ustekinumab

Study Results

No Results Posted as of Aug 22, 2022