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

Phase 1

Conditions: Crohn`s Disease (CD)
MedDRA version: 20.0Level: PTClassification code 10011401Term: Crohn's diseaseSystem Organ Class: 10017947 - Gastrointestinal disorders
Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

Registration Number: EUCTR2020-004527-16-DK

Lead Sponsor: Boehringer Ingelheim International GmbH

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 76

Inclusion Criteria

1. Male or female patients.
2. = 18 – = 75 years, at date of signing informed consent.
3. 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.
4. Elevated CRP (= 5 mg/L) OR elevated fecal calprotectin (= 250 µg/g)
5. Symptomatic CD defined as = CDAI 150
6. 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), as assessed by ileo-colonoscopy and confirmed by central independent reviewer(s) before start of study treatment.
7. •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.
8. May be receiving a therapeutic dose of the following:
o Oral 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
o 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. [Allowed steroid treatments: Locally administered steroids as e.g. intra-articular, nasal inhalation or intra-ocular
administration are allowed.] and/or
o AZA, MP, 6-TG or MTX, provided that dose has been stable for the 8 weeks immediately prior to randomisation and must continue on this dose until week 12.
9. Women of childbearing potential (WOCBP)1 must be ready and able to use highly effective methods of birth control per International Councila on Harmonisation (ICH) M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly. A list of contraception methods meeting these criteria is provided in the patient information or in Section 4.2.2.3.
10. Signed and dated written informed consent in accordance with ICH- Good Clinical Practice (GCP) and local legislation prior to admission to the trial.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 68
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 8

Exclusion Criteria

1. Have any current or prior abscesses, unless they have been drained and treated at least 6 weeks prior to rand 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 comp. 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 inflammatory bowel disease (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 rand
any biologic treatment with a TNF-alpha antagonist (adalimumab, infliximab, golimumab, certolizumab pegol) or vedolizumab (or a
biosimilar) within 4 weeks prior to rando. (If drug level testing for previously used biologic treatment confirms no detectable drug level before rand, patient can be enrolled despite not having completed 4 week from last treatment)
any previous treatment with ustekinumab or (a biosimilar)
any previous treatment with an investigational (or subsequently
approved) non-biologic/biologic drug for CD
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 rand
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 randomisation. Re screening can be undertaken following documented successful treat, no sooner than 1 week after last intake of antimicrobial therapy. If stool examination for C. Diff is indeterminate (toxin A/B pos and GDH antigen negative or toxin A/B negative and GDH antigen pos), a reflex PCR test must be done to assess eligibility. A positive PCR test will lead to excl
7. Evidence of colonic moderate/severe mucosal dysplasia or colonic adenomas, unless properly removed
8. Fecal transplant = 30 days prior to rand
9. Increased risk of infectious complics (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 randomiz.
10. Live or attenuated vaccination within 4 weeks prior to rand
11. Have received BCG vaccines = 1 year prior to randomisation.
12. Active or latent TB:
- Patients with active tuberculosis are excluded.
- Patients will be screened with Interferon Gamma Release Assay (IGRA) such as QuantiFERON or T spot, the patient may also be evaluated for the presence of TB with any additional test required by local practice. Patients with positive test results are excluded unless patient is known to have had a pre

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: 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.<br><br>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.;Secondary Objective: Not applicable;Primary end point(s): Absolute change from baseline in Simple Endoscopic Score for Crohn’s disease (SES-CD) at week 12.;Timepoint(s) of evaluation of this end point: 12 weeks

Secondary Outcome Measures

Name	Time	Method

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