To test the hypothesis that mirikizumab is superior to placebo in inducing clinical remission at Week 12 in patients with moderately to severely active ulcerative colitis (UC)
ID
Source
Brief title
Condition
- Gastrointestinal inflammatory conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint is clinical remission at Week 12 (mirikizumab versus
placebo). Clinical remission is based on the MMS and is defined in protocol.
Secondary outcome
The MMS and the composite SF and RB score, derived from assessment of the Mayo
score, will be used to determine the major secondary endpoints. The major
secondary endpoints are as follows:
- Clinical response at Week 12.
- Endoscopic remission at Week 12.
- Symptomatic remission at Week 4.
- Symptomatic remission at Week 12.
- Clinical response at Week 12 in the biologic-failed population
Background summary
Ulcerative colitis is a chronic disease of unknown etiology that is
characterized by inflammation of the rectum and colon. Symptoms include
diarrhea, rectal bleeding (RB), urgency, and tenesmus (a feeling of incomplete
evacuation of the rectum after defecation). Ulcerative colitis has a relapsing*
remitting course, meaning that many patients have intermittent disease flares
that are interspersed with periods of remission. Treatment goals in UC include
induction of remission (typically within a 6 to 12 week time frame) and
maintenance of remission in the longer term (assessed over 52 weeks of
continuous treatment in clinical trials). In both clinical practice and in
clinical trials, clinical response and clinical remission are assessed by a
combination of endoscopy (improvement in the endoscopic appearance of the
mucosa and healing of ulcers) and patient-reported outcomes, including a
reduction in stool frequency (SF) and a resolution of RB. Control of intestinal
inflammation in UC is also associated with a reduction in the risk of
hospitalization, colectomy, and in the longer term, UCassociated dysplasia and
colorectal cancer.
Study objective
To test the hypothesis that mirikizumab is superior to placebo in inducing
clinical remission at Week 12 in patients with moderately to severely active
ulcerative colitis (UC)
Study design
Study AMAN is a multicenter, randomized, double-blind, parallel-arm,
placebo-controlled study designed to evaluate the safety and efficacy of
mirikizumab, compared with placebo, over a 12-week induction period.
Approximately 2230 patients will be screened to achieve approximately 1160
randomized patients.
Intervention
This study involves a comparison of IV administration of mirikizumab versus
placebo during a 12-week induction period. Mirikizumab or Placebo is given as
an intravenous infusion (Weeks 0, 4, 8).
Study burden and risks
At the time of this benefit/risk assessment, evaluation of unblinded safety
data from the completed or ongoing clinical studies, including the unblinded
period of the Study AMAC, which tests mirikizumab IV every 4 weeks (Q4W), have
not revealed any dose-related safety or tolerability concerns. In addition,
evaluation of blinded safety data in ongoing studies in psoriasis, UC and
Crohn*s disease (CD) with mirikizumab SC Q4W administered up to 92 weeks, and
IV Q4W for up to 52 weeks have not revealed safety or tolerability concerns.
Across ongoing studies, immediate hypersensitivity reactions, including serious
nonfatal anaphylaxis, have been reported at the onset or during IV infusion of
mirikizumab. As noted in the IB, such reactions are considered by the sponsor
to be related to mirikizumab and hence have been identified as adverse drug
reactions (ADRs) .
Consult the most current IB for information regarding ADRs and potential risks
with mirikizumab.
Lilly Corporate Center DC1526
Indianapolis, Indiana 46285
US
Lilly Corporate Center DC1526
Indianapolis, Indiana 46285
US
Listed location countries
Age
Inclusion criteria
1. Male or female patients *18 and *80 years of age at the time of initial screening
2. Diagnosis of UC for at least 3 months prior to baseline.
3. Confirmed diagnosis of moderately or severely active UC, as assessed by the modified Mayo score (MMS).
4. Demonstrated an inadequate response to, a loss of response to, or an intolerance to conventional or to biologic therapy for UC.
5. If female, must meet the contraception requirements.
Exclusion criteria
1. Patients with a current diagnosis of Crohn's disease or inflammatory bowel disease-unclassified (indeterminate colitis).
2. Patients with a previous colectomy.
3. Patients with current evidence of toxic megacolon.
4. Prior exposure to anti-IL12p40 antibodies (e.g. ustekinumab) or anti- IL-23p19 antibodies (e.g. risankizumab, brazikumab, guselkumab or tildrakizumab).
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 | EUCTR2017-003229-14-NL |
| CCMO | NL65500.018.18 |