This study has been transitioned to CTIS with ID 2022-502841-91-00 check the CTIS register for the current data. The main reason for this study is to help in answering the following research question: - Whether mirikizumab can help patients with…
ID
Source
Brief title
Condition
- Gastrointestinal inflammatory conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
- Proportion of participants achieving clinical remission by CDAI (defined as
CDAI score <150) at Week 52 of AMAX
- Proportion of participants achieving endoscopic response (defined by >=50%
reduction from baseline in SES-CD Total Score) at Week 52 of AMAX
Secondary outcome
Key Secondary measures for subjects participating from study AMAM and that
achieved endpoints at Week 52:
1. Proportion of participants achieving endoscopic response at Week 156 of AMAX
2. Proportion of participants achieving endoscopic remission (defined as SES-CD
Total Score <=4 and at least a 2-point reduction from baseline and no sub-score
>1) in AMAX at:
a. Week 52
b. Week 156
3. Proportion of participants achieving clinical remission by PRO (defined as
SF <=3 and not worse than baseline [as per Bristol Stool Scale Category 6 or 7]
and AP <=1 and not worse than baseline) in AMAX at:
a. Week 52
b. Week 100
c. Week 156
4. Proportion of participants achieving clinical response by PRO (defined as at
least a 30% decrease in stool frequency and/or abdominal pain, and no worse
than baseline) in AMAX at:
a. Week 52
b. Week 100
c. Week 156
5. Proportion of participants achieving clinical remission by CDAI (CDAI score
<150) in AMAX at:
a. Week 12
b. Week 52
c. Week 100
d. Week 156
6. Proportion of participants achieving endoscopic response in AMAX at:
a. Week 52
b. Week 156
7. Proportion of participants achieving clinical remission by PRO in AMAX at:
a. Week 52
b. Week 100
c. Week 156
8. Proportion of participants achieving clinical response by PRO in AMAX at:
a. Week 52
b. Week 100
c. Week 156
9. Proportion of participants who achieve clinical remission by PRO or
endoscopic remission who are CS-free at Week 52 of AMAX
10. Proportion of participants who achieve clinical remission by PRO or
endoscopic remission who are CS-free at Week 156 of AMAX
Key Secondary measures for subjects participating from study AMAM and that did
not achieve endpoints at Week 52:
1. Proportion of participants achieving endoscopic response in AMAX at:
a. Week 52
b. Week 156
2. Proportion of participants achieving endoscopic remission in AMAX at:
a. Week 52
b. Week 156
3. Proportion of participants achieving clinical remission by PRO in AMAX at:
a. Week 52
b. Week 100
c. Week 156
4. Proportion of participants achieving clinical response by PRO in AMAX at:
a. Week 52
b. Week 100
c. Week 156
5. Proportion of participants achieving clinical remission by CDAI in AMAX at:
a. Week 52
b. Week 100
c. Week 156
6. To evaluate the following endpoints:
a. C-reactive protein at Week 12 of AMAX
b. Faecal calprotectin at Week 12 of AMAX
c. Proportion of participants with clinical response by PRO at Week 12 of AMAX
d. Proportion of participants with clinical remission by PRO at Week 12 of AMAX
7. Proportion of participants achieving endoscopic response in AMAX at:
a. Week 52
b. Week 156
8. Proportion of participants achieving clinical remission by PRO in AMAX at:
a. Week 52
b. Week 100
c. Week 156
9. Proportion of participants achieving clinical response by PRO in AMAX at:
a. Week 52
b. Week 100
c. Week 156
Key Secondary measures for subjects participating from study AMAM, irrespective
of their prior treatment and endpoint achievement:
1. Proportion of participants achieving endoscopic response in AMAX at:
a. Week 52
b. Week 156
2. Proportion of participants achieving endoscopic remission in AMAX at:
a. Week 52
b. Week 156
3. Proportion of participants with clinical remission by PRO in AMAX at:
a. Week 52
b. Week 100
c. Week 156
4. Proportion of participants with clinical remission by CDAI in AMAX at:
a. Week 12
b. Week 52
c. Week 100
d. Week 156
5. Proportion of participants achieving CS-free clinical remission by PRO or
endoscopic remission in AMAX at:
a. Week 52
b. Week 156
6. The following scores over time during AMAX:
a. Bowel Urgency NRS in AMAX at Week 12, Week 52, Week 100, and Week 156
b. WPAI-CD in AMAX at Week 12
c. EQ-5D-5L in AMAX at Week 12
d. FACIT-Fatigue in AMAX at Week 12, Week 52, Week 100, Week 156
e. IBDQ in AMAX at Week 12, Week 52, Week 100, Week 156
f. PGIC in AMAX at Week 12
g. PGRS in AMAX at Week 12, Week 52, Week 100, and Week 156
Background summary
A sizable proportion of the population with moderately-to-severely active
Crohn's Disease (CD) is unresponsive to, fail to tolerate, or lose response to
conventional therapies or approved biologic therapies
IL-23 which is a protein in the body plays a predominant role in inflammatory
bowel disease (IBD). The relationship of this protein to IBD has been explored
in several studies. The results of these studies indicate that IL-23 promotes
intestinal inflammation. Data from some studies suggest that inhibition of
IL-23 may provide efficacy in CD.
Mirikizumab binds the IL-23p19 subunit of human IL-23 and prevents binding of
IL-23 to the IL-23 receptor, neutralizing the activity of human IL-23.
Several clinical studies of mirikizumab have been completed or are currently
ongoing in patients with psoriasis, ulcerative colitis (UC), and CD.
Mirikizumab has demonstrated efficacy in these studies. In the Phase 2 CD Study
AMAG, treatment with mirikizumab has shown clinically relevant and consistent
treatment effect in reducing or resolving endoscopic inflammation and
patient-reported symptoms in patients with moderately-to-severely active CD.
Evaluation of unblinded safety data in ongoing studies have shown a safety
profile generally consistent with the IL-23 antibody class. Given the data from
the Phase 2 study in CD and data from other clinical studies completed to date,
potential benefits to participants who receive mirikizumab while participating
in this study may be reasonably anticipated.
Study objective
This study has been transitioned to CTIS with ID 2022-502841-91-00 check the CTIS register for the current data.
The main reason for this study is to help in answering the following research
question:
- Whether mirikizumab can help patients with Crohn*s disease when taken for a
longer time.
- How safe mirikizumab is and whether you might have any side effects when you
take it for a long time.
Study design
Study AMAX is a Phase 3, multicentre, long-term extension study evaluating the
efficacy and safety of mirikizumab in participants with moderately-to-severely
active Crohn's Disease (CD) who have participated in an originator adult
mirikizumab CD study, inclusive of the Phase 3 Study AMAM
and the Phase 2 Study AMAG.
Participants who are considered Responders (Response defined as >=50% reduction
from baseline in SES-CD Total Score) in the originator Study AMAM and
participants from Study AMAG will receive open-label mirikizumab subcutaneously
(SC) for an extended period of time (up to 3 years) and then enter a 12- to
16-week post treatment follow-up period. Participants who are considered
Non-responders in the originator Study AMAM will receive an induction treatment
inclusive of 3 intravenous (IV) doses of mirikizumab and continue onto SC
mirikizumab if clinical benefit is shown post-IV induction doses.
Participants who meet all of the inclusion criteria and none of the exclusion
criteria of AMAX, and who, in the opinion of the investigator, would receive
benefit from open-label treatment with mirikizumab are eligible for enrolment
into Study AMAX. It is possible that some participants enrolling from Study
AMAM may have received placebo only in the originating study. These
participants will receive mirikizumab for the first time in Study AMAX.
Intervention
During the study, all participants will receive mirikizumab once every 4
weeks. All participants coming from Study AMAG will take mirikizumab as an
injection under the skin. Participants coming from Study AMAM whose endoscopy
results did not show the required improvement will receive their first 3 doses
in this study as an intravenous (IV) injection. After the first 3 doses,
participants from this group who show improvement will receive additional doses
as injections under the skin. Other participants coming from Study AMAM whose
endoscopy results showed the required improvement will take all doses of
mirikizumab as injections under the skin.
Study burden and risks
Potential benefits to participants who receive mirikizumab while participating
in Study AMAX may be reasonably anticipated, given the data obtained from the
Phase 2 study in Crohn*s Disease (CD) and data from other clinical studies
completed to date.
Immediate hypersensitivity reactions, including infusion-related
hypersensitivity events consistent with anaphylaxis at the onset or during IV
infusion of mirikizumab have been reported in ongoing studies. The protocol
includes specific measures for reducing the incidence and for management of
such events, including management of study drug infusion rate and observation
during and after infusion.
Detailed monitoring and management guidance will be provided to investigators,
in the study protocol and Investigator*s Brochure (IB). This guidance is based
on standard drug registration topics, safety findings from previous studies,
potential risks, published literature, and co-morbidities and risk factors
prevalent in the studied populations
In addition, an independent, external data monitoring committee (DMC) will
review clinical trial data at pre-specified, regular intervals during the
study. This independent assessment of clinical trial data will contribute to
the overall ongoing evaluation and management of potential risks associated
with mirikizumab administration.
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Island House, Eastgate Business Park, Little Island na
Cork T45 KD39
IE
Listed location countries
Age
Inclusion criteria
Some of the important criteria for study participants to be eligible for
inclusion in the study are (please refer section 5.1 of the protocol for more
details):
1. They have given written informed consent
2. They have participated in the Phase 2 Study AMAG and have:
a. completed the last visit of participation in the AMAG study and remained on
mirikizumab treatment in either the maintenance dosing period 3 or in the AMAG
extension period, and
b. in the opinion of the investigator, would derive clinical benefit from
continued treatment with mirikizumab.
It is preferred that participants receive the first dose of AMAX study drug
within approximately 6-8 weeks of the last dosing visit in AMAG. A maximum of
18 weeks will be allowed between the last dose in AMAG and the first dose in
AMAX to accommodate situations where due to circumstances outside the patient's
control, a patient may not be able to complete all required assessments within
the recommended shorter window.
3. They have participated in the Phase 3 Study AMAM and have:
a. completed Week 52 of the AMAM study, including the Week 52 endoscopy for
evaluation of Responder/Non-responder status, and in the opinion of the
investigator would derive clinical benefit from treatment with mirikizumab.
It is preferred that participants receive the first dose of AMAX study drug
within approximately 6-8 weeks after the last dosing visit in AMAM. A maximum
of 18 weeks will be allowed between the last dose in AMAM and the first dose in
AMAX to accommodate situations where due to circumstances outside the patient's
control, a patient may not be able to complete all required assessments within
the recommended shorter window.
4. They are willing and able to complete the scheduled study assessments,
including endoscopy, self-administer investigational product (or have caregiver
administer investigational product), and complete patient electronic and paper
diary.
5. They have clinically acceptable central laboratory test results at study
entry which would not have resulted in permanent discontinuation of treatment
in the originator study.
6. Contraception
a. Male Participants: No male contraception is required
b. Female Participants:
i. Women of childbearing potential: must test negative for pregnancy prior to
initiation of treatment as indicated by a negative urine pregnancy test at
Visit 1/Week 0 of this study
AND
ii. must agree to either remain abstinent, if complete abstinence is their
preferred and usual lifestyle, or remain in same-sex relationships, if part of
their preferred and usual lifestyle, without sexual relationships with males.
Periodic abstinence (for example, calendar, ovulation, symptothermal, or
post-ovulation methods), declaration of abstinence just for the duration of a
trial, and withdrawal are not acceptable methods of contraception,
OR
iii. must use a combination of 2 effective methods of contraception or 1 highly
effective method of contraception for the entirety of the study. Abstinence or
contraception must continue following completion of study drug administration
for 16 weeks.
iv. Women not of childbearing potential may participate and include those who
are:
a) infertile due to surgical sterilization (total hysterectomy, bilateral
salpingo-oophorectomy, bilateral salpingectomy, bilateral oophorectomy or tubal
ligation), a congenital anomaly such as Müllerian agenesis, or
b) postmenopausal
Exclusion criteria
Some of the important criteria for study participants to be excluded from the
study are (please refer section 5.2 of the protocol for more details):
3. They had a reported serious adverse event (SAE) in originator study or
developed other condition prior to AMAX Week 0 that would disqualify them from
treatment with mirikizumab according to originator study criteria.
4. Had permanently discontinued study drug in the originator study or had a
temporary interruption of study drug in originator study such that, in the
opinion of the investigator or Sponsor, restarting of mirikizumab would pose an
unacceptable risk for the participant in Study AMAX.
5. Presence of significant uncontrolled neuropsychiatric disorder or judged at
risk of suicide in the opinion of the investigator
6. Have a known hypersensitivity to any component of this investigational
product or monoclonal antibodies or has experienced an acute systemic
hypersensitivity event with previous study drug administration that precludes
mirikizumab therapy.
7. Are pregnant, lactating, or planning to become pregnant while enrolled in
the study or within 16 weeks after receiving the last dose of study drug.
9. Intend to receive a Bacillus Calmette Guerin (BCG) vaccination or a live
attenuated vaccine during the study.
10. Have any history or current evidence of cancer of the gastrointestinal
tract.
11. Have any current sporadic adenoma without dysplasia that has not been
removed. Once completely removed, the patient is eligible for the study.
12. Have any evidence of colonic dysplasia.
13. Are currently enrolled in any other clinical study involving an
investigational product or any other type of medical research judged not to be
scientifically or medically compatible with this study.
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 |
|---|---|
| EU-CTR | CTIS2022-502841-91-00 |
| EudraCT | EUCTR2019-002687-27-NL |
| ClinicalTrials.gov | NCT04232553 |
| CCMO | NL72760.028.20 |