The primary objectives of this trial are:- To explore the pathomechanisms involved in the generation and healing of CD associated perianal fistulas- To understand the MoA of BI 655130 in patients with CD and draining perianal fistulas
ID
Source
Brief title
Condition
- Gastrointestinal inflammatory conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint is the total number of deregulated genes at week 4
comparing changes in gene expression from baseline between the two treatment
groups.
See details in protocol section 2.1.2.
Secondary outcome
The secundary endpoints for this study are:
- Proportion of patients with perianal fistula response at week 12
- Proportion of patients with perianal fistula remission at week 12
- Proportion of patients with combined perianal fistula remission at week 12
See details in protocol section 2.1.3.
Background summary
Fistulas represent one of the most important complications in patients with CD.
The number of patients with severe and recurrent problems arising from CD
fistulas is considerably high. Surgery, though often required, does not always
provide a definitive cure. Current treatments with medications show limited
efficacy. Thus, there remains a significant unmet Medical need for better
treatments of this CD complication
See also protocol section 1.1.
Study objective
The primary objectives of this trial are:
- To explore the pathomechanisms involved in the generation and healing of CD
associated perianal fistulas
- To understand the MoA of BI 655130 in patients with CD and draining perianal
fistulas
Study design
This trial is divided into two cohorts: a screening cohort and a study cohort.
The Netherlands will only participate in the study cohort.
The Study Cohort is designed as a randomized, double-blind and
placebo-controlled, parallelgroup, phase IIa study of BI 655130, an anti IL-36R
antibody, in patients with perianal fistulizing CD. Once the gene expression
analyses from the obtained fistula canal samples in the screening cohort have
confirmed the eligibility criteria, enrolment of the study cohort will be
initiated. Otherwise, the sponsor may decide to amend the study (via
substantial amendment) in order to obtain the relevant tissue from all study
participants.
The Study Cohort will consist of:
- screening period, including fistula preparation visits
- period 1: 12-week blinded intravenous therapy period
- period 2: 12-week blinded intravenous therapy period (treatment assignment
depends on randomized treatment and achievement of combined perianal fistula
remission after treatment period 1)
- Roll over into open label long-term extension study 1368-0007 after end of
trial OR 12-week safety follow up period for patients not rolling-over into
open label longterm extension study 1368-0007 (corresponding to 16 weeks after
the last dose of BI 655130)
See protocol section 3.1.
Intervention
Study Cohort, Period 1: Double blind.
During visit 2 eligible patients in Study Cohort will be randomised to receive
12 weeks of treatment (i.e. three administrations) with BI 655130 1200mg i.v.
every 4 weeks or matching placebo in a 1:1 ratio according to a randomization
plan.
Study Cohort, Period 2: Double blind
Treatment in period 2 starting in visit 6 (BI 655130 1200mg i.v. every 4 weeks
or placebo) will be determined by the outcome at week 12 (cf. section 3.1).
See protocol section 4.1 - 4.1.4.
Study burden and risks
This is a newly developed drug that is still in the early stage of research and
therefore benefits for the patient can not be guaranteed. However,
participation in the study is of great importance to investigate the safety,
tolerability and dosage of BI655130.
Patients are exposed to the risks of the screening procedures and the risks
associated with the exposure to the study medication.
The total duration of the study for a patient is a maximum of 41 weeks.
Patients have a risk of (unknown) side effects, an allergic reaction to the
study medication, pain due to blood sampling or irritated skin due to the
electrodes used in making the ECGs, discomfort and (small) risk for
complications during endoscopy's (Ileocolonoscopy / Rectoscopy / Proctoscopy)
and biopsy's.
See protocol section 1.4.
Comeniusstraat 6
Alkmaar 1817MS
NL
Comeniusstraat 6
Alkmaar 1817MS
NL
Listed location countries
Age
Inclusion criteria
1) 18-75 years at date of signing informed consent
2) Male or female patients. Women of childbearing potential must be ready and
able to use highly effective methods of birth control as mentioned in the
protocol.
3) Diagnosis of clinical Crohn*s Disease >= 3 months prior to screening by
clinical and
endoscopic evidence and corroborated by a histopathology report
4) Has >= 1 perianal active* fistula(s) with clinical indication for seton
drainage (>= 4 weeks
duration before enrolment, as a complication of CD) **.
* Criteria for Active Fistula: As per clinical evaluation: Presence of
spontaneous
drainage or drainage after gentle finger compression at the external openings
and as
confirmed by radiological (MRI) exploration .
** Patients who are screened with a seton drainage in place are eligible
provided the
drainage has not been in place for > 3 months and the patient meets the rest of
the
eligibility criteria
5) Additional enterocutaneous or abdominal fistulas are permitted (except
rectovaginal
fistulas)
6) Absent, mild or moderate clinical activity with CDAI of 250 or less.
7) Demonstrated in the past inadequate response or loss of response or have had
unacceptable side effects with approved doses of at least one of the following
compounds: Immunesuppressive agents (e.g. thiopurines, methotrexate),
TNF* antagonists (e.g. infliximab, adalimumab, certolizumab pegol; or respective
biosimilars), vedolizumab, ustekinumab, azathioprine and / or antibiotics
8) Patients with family history of colorectal cancer or personal history of
increased
colorectal cancer risk must have had a negative ileocolorectal cancer screening
within <1
year prior to screening per local guidance (otherwise to be done during
screening
ileocolonoscopy).
9) Signed and dated written informed consent
Exclusion criteria
1) Complications of Crohn*s Disease such as symptomatic strictures, functional
stenosis
distal from fistula(s), short gut syndrome, or any other manifestation that
might require
surgery,
2) Rectovaginal fistulas
3) Anticipated to require surgical intervention for CD including any fistula
surgical procedures (except seton drainage).
4) Has an abscess that the investigator feels requires drainage beyond fistula
drainage with a
seton
5) Any kind of bowel resection or diversion within 6 months or any other
intraabdominal
surgery within 3 months prior to screening.
6) Ileostomy, colostomy or known fixed symptomatic stenosis of the intestine at
screening.
7) Positive stool examinations for C. difficile or other intestinal pathogens
< 30 days prior to
screening
8) Evidence of colonic mucosal dysplasia or colonic adenomas, unless properly
removed
(properly according to the investigator*s assessment)
9) Faecal transplant <= 6 months before screening, Further criteria apply.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2017-003090-34-NL |
| ClinicalTrials.gov | NCT03752970 |
| CCMO | NL67902.056.18 |