A study to test whether BI 706321 combined with ustekinumab helps people with Crohn's Disease

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Boehringer Ingelheim International GmbH

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

Trial duration

17 Feb 2022 → 8 Aug 2024

Decision date (initial)

2024-07-23

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2024-512756-38-00

EudraCT number

2020-004527-16

ClinicalTrials.gov

NCT04978493

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Pharmacokinetic, Pharmacodynamic

The main objectives of this trial are to investigate a first signal of efficacy, safety and tolerability of BI 706321 in combination with ustekinumab treatment compared to placebo with ustekinumab treatment in patients with moderately to severely active CD at 12 weeks.

The primary objective is to estimate the difference in change from baseline in Simple Endoscopic Score for Crohn's disease (SES-CD) after 12 weeks. The primary treatment comparison will be between treatment groups while on treatment during the 12 week induction period.

Conditions and MedDRA coding

Crohn`s Disease (CD)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Diagnosis of 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.
2. Elevated CRP (≥ 5 mg/L) OR elevated fecal calprotectin (≥ 250 μg/g)
3. Symptomatic CD defined as ≥ CDAI 150
4. Presence of mucosal ulcers in at least one segment of the ileum or colon and a SESCD score ≥ 7 (for patients with isolated ileitis ≥4)
5. Patients who are experienced to at least 1 tumor necrosis factor (TNF) antagonist 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.
6. May be receiving a therapeutic dose of the following: Oral 5-ASA compounds Oral corticosteroids AZA, MP, 6-TG, or MTX
7. Women of childbearing potential (WOCBP)1 must be ready and able to use highly effective methods of birth control
8. Further inclusion criteria apply.

Exclusion criteria 12

1. Have any current or prior abscesses, unless they have been drained and treated at least 6 weeks prior to randomization 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
2. 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 SESCD/ CDAI to assess response to therapy, or would possibly confound the evaluation of benefit from treatment with BI 706321
3. Patient with an IBD diagnosis other than CD
4. Have had any kind of bowel resection or diversion within 4 months or any other intraabdominal surgery within 3 months prior to visit 1. Patients with current ileostomy, colostomy, or ileorectal anastomosis are excluded.
5. Treatment with: - any non-biologic medication for IBD (tacrolimus or mycophenolate mofetil, systemic corticosteroids), other than those allowed per inclusion criteria, within 30 days prior to randomization - any biologic treatment with a TNF-alpha antagonist (adalimumab, infliximab, golimumab, certolizumab pegol) or vedolizumab (or a biosimilar) within 4 weeks prior to randomization. - 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.
6. Positive stool examination for C difficile (toxin A/B and GDH ag – test positive) or other intestinal pathogens <30 days prior to randomization.
7. Evidence of colonic moderate/severe mucosal dysplasia or colonic adenomas, unless properly removed
8. Increased risk of infectious complications (e.g. recent pyogenic inf, any congenital or acquired immunodeficiency (e.g. Human immunodeficiency virus), 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 w prior to randomization BCG vaccines ≤ 1 year prior to randomization
9. Live or attenuated vaccination within 4 weeks prior to randomization
10. Presence of clinically significant acute or chronic infections not otherwise listed, including viral hepatitis, COVID-19, or others based on investigator's judgement.
11. 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 ECG finding at screening. Both have to be confirmed by repeated ECG recording.
12. Further exclusion criteria apply

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Absolute change from baseline in Simple Endoscopic Score for Crohn's disease (SES-CD) at week 12.

Secondary endpoints 11

1. Percent change in SES-CD from baseline at Week 12-
2. Endoscopic response (defined as ≥50% 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
3. Endoscopic response (defined as ≥50% 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
4. Endoscopic remission (defined as SES-CD score of ≤2) at week 12
5. Endoscopic remission (defined as SES-CD score of ≤2) at week 48
6. Biological remission, defined as C-reactive protein (CRP) <5 mg/L and faecal calprotectin (FCP) < 250 ug/g at week 12
7. Biological remission, defined as CRP < 5 mg/L and FCP <250 ug/g at week 48
8. Clinical remission at week 12, defined as a Crohn's Disease Activity Index (CDAI) score of <150
9. Clinical remission at week 48, defined as a 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 residual effect period (REP) (i.e. through Visit 9)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Placebo 1

Auxiliary 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Boehringer Ingelheim International GmbH

Sponsor organisation

Boehringer Ingelheim International GmbH

Address

Binger Strasse 173

City

Ingelheim Am Rhein

Postcode

55216

Country

Germany

Scientific contact point

Organisation

Boehringer Ingelheim International GmbH

Contact name

CT disclosure & Data Transparency

Public contact point

Organisation

Boehringer Ingelheim International GmbH

Contact name

CT disclosure & Data Transparency

Third parties 1

Locations

6 EU/EEA countries · 28 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 9 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications