To test the hypothesis that mirikizumab is superior to placebo in maintaining clinical remission at Week 40 (Week 52 of continuous therapy) among patients induced into clinical remission with mirikizumab
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 40 among patients induced
into clinical remission with mirikizumab induction treatment (Study AMAN).
Clinical remission is based on the MMS and is defined in protocol.
Secondary outcome
- Clinical remission at Week 40, among patients induced into clinical response
(that is, demonstrating clinical response or clinical remission) with
mirikizumab at Week 12 of induction study (Study AMAN)
- Endoscopic remission at Week 40, among patients induced into clinical
response with mirikizumab at Week 12 of the induction study
- Corticosteroid-free remission without surgery at Week 40, among patients
induced into clinical response with mirikizumab during the induction study and
who were receiving corticosteroids at induction baseline. For Week 40, this
endpoint is defined as:
o Clinical remission at Week 40, and
o Symptomatic remission at Week 28, and
o No corticosteroid use for *12 weeks prior to Week 40
- Evaluate, in the subgroup of patients in whom biologic agents have failed or
caused intolerance, clinical remission at Week 40 among patients induced into
clinical response with mirikizumab
- Evaluate, in the subgroup of patients in whom biologic agents have failed or
caused intolerance, endoscopic remission at Week 40 among patients induced into
clinical response with mirikizumab
- Histologic remission at Week 40, among patients induced into clinical
response with mirikizumab
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 maintaining
clinical remission at Week 40 (Week 52 of continuous therapy) among patients
induced into clinical remission with mirikizumab
Study design
Study AMBG is a phase 3, multicenter, randomized, double-blind, parallel-arm,
placebo-controlled study designed to evaluate the safety and efficacy of
mirikizumab every 4 weeks (Q4W) subcutaneous (SC) in maintaining treatment
response at Week 40 (that is, at Week 52 of continuous study drug treatment).
Intervention
Patients who achieved clinical response with blinded mirikizumab treatment
during Study AMAN will be randomized 2:1 to blinded mirikizumab Q4W SC or
blinded placebo.
Patients who responded to blinded placebo in their induction study will remain
on blinded placebo in Study AMBG. Open-label rescue therapy with mirikizumab
Q4W intravenous (IV) will be administered for 3 doses if these patients lose
response.
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. Have completed Study AMAN, with at least 1 study drug administration,
without early termination of study drug, and underwent a Visit 5 (Week 12)
endoscopy.
2. Are willing and able to complete the scheduled study assessments, including
endoscopy and daily diary entry.
3. If female, must meet the contraception requirements.
Exclusion criteria
1. Participants diagnosed with Crohn's disease or inflammatory bowel
disease-unclassified (indeterminate colitis) during the induction study
AMAN.
2. Participants with a bowel resection or other surgery for the treatment
of UC during the previous induction study AMAN, or are likely to require
surgery for the treatment of UC during study AMBG.
3. Participants with evidence of colonic dysplasia or have been diagnosed with
cancer of the gastrointestinal tract during study AMAN.
4. Participants diagnosed with clinically important infection including, but
not limited to, hepatitis B, hepatitis C, HIV/AIDS, and active tuberculosis
(TB) during the induction study AMAN.
5. Participants who initiate a new prohibited medication during the induction
study AMAN.
6. Participants with certain laboratory abnormalities prior to start of AMBG
that would require permanent discontinuation from study drug.
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 | EUCTR2017-003238-96-NL |
| CCMO | NL65501.018.18 |