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
- Conditions
- 10017969Inflammatory bowel disease / Crohn's
- Registration Number
- NL-OMON53423
- Lead Sponsor
- Boehringer Ingelheim
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 5
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 by endoscopic,
radiology, and supported by histology.
4. Elevated CRP (>= 5 mg/L) OR elevated fecal calprotectin (>= 250 µg/g)
5. Moderate to severe active CD at visit 1 defined as CDAI >=220 and <=450 (one
rescreening is allowed).
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 1 or 2 TNF antagonists (i.e. biosimilars of
a drug are counted as the originator drug, e.g. the switch from infliximab
originator to CT-P13 will count as one TNF antagonist exposure) at a dose
approved for CD. Patients may have stopped TNF antagonists treatment due to
primary or secondary nonresponsiveness, 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-thioguanine (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 Council a on
Harmonisation (ICH) M3 (R2) that result in a low failure rate of less than 1%
per year when used consistently and correctly.
10. Signed and dated written informed consent in accordance with ICH Good
Clinical Practice (GCP) and local legislation prior to admission to the trial.
1. 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.
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 (based on investigator's judgement).
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 (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) 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)
- 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], 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.
6. Positive stool examination for C difficile (toxin A/B - test positive) or
other intestinal pathogens <30 days prior to randomisation. Rescreening can be
undertaken following documented successful
treatment, no sooner than 1 week after last intake of antimicrobial therapy.
7. Evidence of colonic moderate/severe mucosal dysplasia or colonic adenomas,
unless properly removed.
8. Fecal transplant <= 30 days prior to randomisation.
9. 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.
10. Live or attenuated vaccination within 4 weeks prior to randomisation.
11. Have received BCG vaccines <= 1 year prior to randomisation.
12. Active or latent TB:
- Patients with active tuberculosis are excluded.
- Patients will b
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Absolute change from baseline in Simple Endoscopic Score for Crohns disease<br /><br>(SES-CD) at week 12.</p><br>
- Secondary Outcome Measures
Name Time Method