The objective is to evaluate the efficacy and safety of risankizumab versus placebo during induction therapy in subjects with moderately to severely active CD.
ID
Source
Brief title
Condition
- Gastrointestinal inflammatory conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Proportion of participants with clinical remission and proportion of
participants with endoscopic response at Week 12.
Secondary outcome
1. Proportion of subjects with CDAI clinical remission at Week 12
2. Proportion of subjects with CDAI clinical response at Week 4
3. Proportion of subjects with clinical remission at Week 4
4. Proportion of subjects with CDAI clinical response at Week 12
5. Mean change from baseline of induction in FACIT fatigue at Week 12
6. Mean change from baseline of induction in IBDQ total score at Week 12
7. Proportion of subjects with enhanced clinical response and endoscopic
response at Week 12
8. Proportion of subjects with endoscopic remission at Week 12
9. Proportion of subjects with enhanced clinical response at Week 4
10. Proportion of subjects with ulcer-free endoscopy at Week 12
11. Enhanced clinical response at Week 12
12. Proportion of subjects with resolution of extra-intestinal manifestations
(EIMs) at Week 12, in subjects with any EIMs at Baseline
13. Proportion of subjects with CD-related hospitalization through Week 12
14. Proportion of subjects without draining fistulas at Week 12 in subjects
with draining fistulas at Baseline
Background summary
The aim of medical treatment in Crohn*s disease (CD) has been focused on
controlling inflammation and reducing symptoms. In addition to improving
symptoms, an emerging goal of therapy is to heal the gut mucosa. Resolution of
intestinal ulcers, also known as mucosal healing has been associated with
positive clinical benefits, including higher rates of clinical remission, fewer
hospitalizations, and fewer abdominal surgeries. However, improvement of the
appearance of the intestinal mucosa may be more difficult to achieve than
symptomatic improvement alone.
Conventional pharmaceutical therapies (e.g., corticosteroids, aminosalicylates,
thiopurines, methotrexate) are limited, do not always completely abate the
inflammatory process, and have significant adverse effects. The advent of
anti-tumor necrosis factor alpha (TNFα) agents (e.g., adalimumab) and integrin
inhibitors (e.g., vedolizumab) have been shown to achieve clinical remission in
patients who are refractory to conventional therapies.
Despite the benefits of available biologic therapies, many patients do not
respond to initial treatment (primary loss of response) or lose treatment over
time (secondary loss of response). Regarding anti-TNFα agents, approximately
40% of patients will experience primary non-response and secondary non-response
occurs in 38% of patients at 6 months and 50% of patients at 1 year.
Additionally, some patients are not candidates for available biologic
therapies. Therefore new therapeutic options are required in order to continue
to improve the outcome of patients with CD.
Study objective
The objective is to evaluate the efficacy and safety of risankizumab versus
placebo during induction therapy in subjects with moderately to severely active
CD.
Study design
This is a phase 3 multicenter, randomized, double-Blind, placebo-controlled
induction study to assess the efficacy and safety of risankizumab in subjects
with moderately to severely active CD.
Intervention
Subjects receive risankizumab or placebo, via IV, during the 12 week induction
period (weeks 0 to 12); subjects with inadequate response receive risankizumab,
via IV or SC, during the 12 week induction period 2 (week 12 to 24).
Study burden and risks
There will be higher burden for subjects participating in this trial compared
to their standard of care. Subject will be visiting the hospital more
frequently. During these visits study procedures will be performed including
blood sampling, physical examinations, and filling in questionnaires. Subject
will also be tested for TB, significant heart conditions, pregnancy, Hepatitis
C/Hepatitis B and Human immunodeficiency virus (HIV). Subjects will also
complete a daily symptom diary. Women of childbearing potential should practice
a highly effective method of birth control, during the study through at least
140 days after the last dose of study drug.
Subjects will either receive risankizumab or placebo during the study. The most
common side effects reported during previous studies of risankizumab were
nausea, abdominal pain, joint pain and headache.
The hypothesis that risankizumab should be effective in targeting inflammation
in patients with CD who are unable to tolerate or who have had insufficient
response to treatment with some current available medication, indicates that
there is an acceptable rationale to conduct this study. The risks and burden
associated with participating in this study are acceptable in regards to the
potential benefit study subjects could possibly have.
Wegalaan 9
Hoofddorp 2132JD
NL
Wegalaan 9
Hoofddorp 2132JD
NL
Listed location countries
Age
Inclusion criteria
- Males or females >= 18 and <= 80 years of age, or minimum age of adult consent
according to local regulations, at the Baseline Visit. Where locally
permissible,
subjects 16 to < 18 years of age who meet the definition of Tanner stage 5 for
development at the Baseline Visit
- Diagnosis of CD for at least 3 months prior to Baseline
- Crohn's disease activity index (CDAI) score 220-450 at Baseline
- Confirmed diagnosis of moderate to severe CD as assessed by stool frequency
(SF), abdominal pain (AP) score, and Simple Endoscopic Score for Crohn's
Disease (SES-CD)
- Demonstrated intolerance or inadequate response to conventional or biologic
therapy for CD
- If female, subject must meet the contraception recommendations
Exclusion criteria
- Subject with a current diagnosis of ulcerative colitis or indeterminate
colitis
- Subjects with unstable doses of concomitant Crohn's disease therapy
- Receipt of Crohn's disease approved biologic agents prior to Baseline (as
detailed in protocol), or any investigational biologic or other agent or
procedure within minimally 35 days prior to the Baseline
- Prior exposure to p19 inhibitors (e.g., risankizumab)
- Complications of Crohn's disease (strictures, short bowel, etc)
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 | EUCTR2016-003123-32-NL |
| ClinicalTrials.gov | NCT03105128 |
| CCMO | NL60410.018.17 |