Primary: To evaluate the efficacy of ontamalimab as maintenance treatment of remission, based on composite score of patient reported symptoms and centrally read endoscopy, in subjects with moderate to severe ulcerative colitis (UC).Key Secondary:*…
ID
Source
Brief title
Condition
- Gastrointestinal inflammatory conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To evaluate the efficacy of ontamalimab as maintenance treatment of remission,
based on composite score of patient reported symptoms and centrally read
endoscopy, in subjects with moderate to severe ulcerative colitis (UC).
Secondary outcome
* To evaluate the efficacy of ontamalimab on endoscopic remission, based on
centrally read endoscopy.
* To evaluate the efficacy of ontamalimab on clinical remission, based on
composite score of patient reported symptoms.
* To evaluate the efficacy of ontamalimab on maintenance of remission among
subjects in remission at baseline of the SHP647-303 study, based on composite
score of patient reported symptoms and centrally read endoscopy.
* To evaluate the efficacy of ontamalimab on clinical response, based on
composite score of patient reported symptoms and centrally read endoscopy.
* To evaluate the efficacy of ontamalimab on mucosal healing, based on a
centrally read endoscopic and histological assessment using the Geboes Score
grading system.
* To evaluate the efficacy of ontamalimab on glucocorticoid free clinical
remission.
* To evaluate the efficacy of ontamalimab on glucocorticoid free remission.
* To evaluate the safety and tolerability of ontamalimab as maintenance
treatment.
* To evaluate the effect of ontamalimab maintenance treatment on other clinical
and endoscopic outcomes (including Mayo-based remission, Mayo-based clinical
response, partial Mayo score over time, clinical remission over time,
endoscopic remission, deep remission, sustained endoscopic remission, sustained
mucosal healing, sustained deep remission, sustained clinical remission,
sustained endoscopic remission, sustained remission, sustained clinical
remission over time, and glucocorticoid-free clinical remission over time).
* To evaluate the effect of ontamalimab on abdominal pain, urgency, diarrhea,
and absolute stool frequency and bleeding scores.
* To evaluate the effect of ontamalimab maintenance treatment on health-related
quality of life (as measured by the Inflammatory Bowel Disease Questionnaire
[IBDQ] and the Short Form-36 Health Survey [SF-36]).
* To evaluate the impact of ontamalimab maintenance treatment on incidence of
hospitalizations and total inpatient days.
Background summary
Ulcerative colitis (UC) is a chronic, relapsing disease marked by ulceration
and inflammation of the colonic mucosa and submucosa. Initially it usually
involves the rectum but may extend proximally to involve a portion of, or the
entirety of, the colon. In the early stages, hemorrhagic and erythematous
tissue is observed, progressing to mucosal ulceration with purulent exudates in
severe cases. The ulceration pattern is continuous and may extend the entire
length of the colon. Perforation of the bowel wall causing ileus and
peritonitis can occur with transmural extension of the ulceration. Bloody
diarrhea with or without mucus and lower abdominal pain with periods of
remission and exacerbation are the most common symptoms.
Although UC can occur at any age, peak incidence has been observed in the
second to fourth decades of life. UC is a lifelong condition with a serious
effect on the quality of life. Current treatment primarily consists of
symptomatic management with dietary modifications and opiates, as well as
disease modifying agents, systemic glucocorticoids, immunosuppressive agents,
and biologic therapy. Despite recent advances, there is still an unmet need for
an effective pharmacological treatment that will induce and maintain remission.
The selectivity of lymphocyte homing to specialized lymphoid tissue and mucosal
sites of the gastrointestinal (GI) tract is influenced by the endothelial
expression of mucosal addressin cell adhesion molecule (MAdCAM). MAdCAM plays a
role in gut immune surveillance, and also appears to facilitate excessive
lymphocyte infiltration under conditions of chronic GI inflammation.
Ontamalimab is a fully human immunoglobulin G2 kappa (IgG2k) monoclonal
antibody that binds to human MAdCAM to reduce lymphocyte homing to the gut and
GI inflammation.
Study objective
Primary: To evaluate the efficacy of ontamalimab as maintenance treatment of
remission, based on composite score of patient reported symptoms and centrally
read endoscopy, in subjects with moderate to severe ulcerative colitis (UC).
Key Secondary:
* To evaluate the efficacy of ontamalimab on endoscopic remission, based on
centrally read endoscopy.
* To evaluate the efficacy of ontamalimab on clinical remission, based on
composite score of patient reported symptoms.
* To evaluate the efficacy of ontamalimab on maintenance of remission among
subjects in remission at baseline of the SHP647-303 study, based on composite
score of patient reported symptoms and centrally read endoscopy.
* To evaluate the efficacy of ontamalimab on clinical response, based on
composite score of patient reported symptoms and centrally read endoscopy.
* To evaluate the efficacy of ontamalimab on mucosal healing, based on a
centrally read endoscopic and histological assessment using the Geboes Score
grading system.
* To evaluate the efficacy of ontamalimab on glucocorticoid free clinical
remission.
* To evaluate the efficacy of ontamalimab on glucocorticoid free remission.
Other Secondary:
* To evaluate the safety and tolerability of ontamalimab as maintenance
treatment.
* To evaluate the effect of ontamalimab maintenance treatment on other clinical
and endoscopic outcomes (including Mayo-based remission, Mayo-based clinical
response, partial Mayo score over time, clinical remission over time,
endoscopic remission, deep remission, sustained endoscopic remission, sustained
mucosal healing, sustained deep remission, sustained clinical remission,
sustained endoscopic remission, sustained remission, sustained clinical
remission over time, and glucocorticoid-free clinical remission over time).
* To evaluate the effect of ontamalimab on abdominal pain, urgency, diarrhea,
and absolute stool frequency and bleeding scores.
* To evaluate the effect of ontamalimab maintenance treatment on health-related
quality of life (as measured by the Inflammatory Bowel Disease Questionnaire
[IBDQ] and the Short Form-36 Health Survey [SF-36]).
* To evaluate the impact of ontamalimab maintenance treatment on incidence of
hospitalizations and total inpatient days.
Study design
This study consists of a 52 week, double-blind treatment period, followed by a
16 week safety follow-up period for subjects who either discontinue treatment
early or who complete the treatment period and do not enter the long-term
safety extension (LTS) study (SHP647-304).
The eligibility of a subject for the study will be assessed based on the study
data collected at the Week 12 visit of the induction studies (SHP647-301),
which will be considered as the baseline visit for this maintenance study.
Subjects enrolled in this study (SHP647-303) will receive double-blind
maintenance treatment in the form of SC injections, using a PFS, every 4 weeks
for 52 weeks. Subjects will undergo efficacy, biomarker, pharmacokinetic,
safety, and health outcome assessments.
Patient-reported UC signs and symptom data (including stool frequency, rectal
bleeding severity and frequency, diarrhea frequency, urgency frequency, and
abdominal pain worst severity) will be collected using a daily e diary for 10
days before each visit. The Mayo score is a measure of UC disease activity
consisting of the following 4 subscores: stool frequency, rectal bleeding,
findings of endoscopy, and physician global assessment (PGA). The partial Mayo
score consists of the Mayo score without the endoscopic subscores. The
composite score is a recommended measure consisting of the Mayo score without
the PGA subscore, and will be used for the primary efficacy endpoint. The Mayo
scores and composite score will be based on subject daily e-diary entries.
Subjects who complete the double-blind treatment period in this maintenance
study may be eligible to enter the LTS study (SHP647-304). Subjects will enter
a 16 week safety follow up period if they withdraw early from the treatment
period, are treatment failures and do not enter the LTS study (SHP647-304), or
who complete the study and do not wish to enter the LTS study.
Intervention
The participants receive a subcutaneous injection every 4 weeks; 1 group with
25 mg ontamalimab, 1 group with 75 mg ontamalimab, and 1 group with placebo.
Study burden and risks
Ontamalimab may cause side effects. The most frequently reported side effects
(in more than 1 out of every 10 subjects) are: joint pain, headache, pain in
the belly, nausea, fever and nasopharyngitis. If the patient receives placebo
there is a possibility that symptoms of the disease may return or get worse.
Also the study procedures may be accompanied by risks and discomforts. In
addition the study drug, the study procedures and the combination of these may
lead to risks that are as yet unknown.
Ulcerative colitis (UC) is a chronic, relapsing disease marked by ulceration
and inflammation of the colonic mucosa and submucosa. Ulcerative colitis is a
lifelong condition with a serious effect on the quality of life. Current
treatment primarily consists of symptomatic management. Despite recent
advances, there is still an unmet need for an effective pharmacological
treatment that will induce and maintain remission.
Considering the chronic and relapsing characteristics of this lifelong disease,
we feel these side effects and the burden associated with participation, are in
proportion considering the positive effects that participation in the study
might have on the patients disease.
Shire Way 300
Lexington MA 02421
US
Shire Way 300
Lexington MA 02421
US
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Age
Inclusion criteria
Subjects must meet all of the following inclusion criteria to be eligible for
enrollment into the study.
1. Subjects and/or their parent or legally authorized representative must have
an understanding, ability, and willingness to fully comply with study
procedures and restrictions.,
2. Subjects must be able to voluntarily provide written, signed, and dated
(personally or via a legally authorized representative) informed consent and/or
assent to participate in the study.,
3. Subjects must have completed the 12-week induction treatment period from
study SHP647-301 or SHP647-302. ,
4. Subjects must have achieved clinical response in induction study SHP647-301
or SHP647-302. Clinical response is defined as:
1) A decrease from the induction study (SHP647-301 or SHP647-302) baseline in
the composite score of patient-reported symptoms using daily e-diary and
centrally read endoscopy of at least 2 points and at least 30%, with an
accompanying decrease in the subscore for rectal bleeding *1 point or a
subscore for rectal bleeding *1
OR
2) A decrease from the induction study (SHP647-301 or SHP647-302) baseline in
total Mayo score of at least 3 points and at least 30%, with an accompanying
decrease in the rectal bleeding subscore of at least 1 point or an absolute
rectal bleeding subscore of 0 or 1.
For eligibility assessment, clinical response will be determined based on the
centrally read endoscopy performed during screening and at Week 12 of induction
study SHP647-301 or SHP647-302.,
5. Subjects receiving any treatment(s) for UC described in Section 5.2.1 of the
protocol are eligible provided they have been, and are anticipated to be, on a
stable dose for the designated period of time.
Exclusion criteria
Subjects are excluded from the study if any of the following criteria are met:,
1. Subjects who had major protocol deviation(s) (as determined by the sponsor)
in induction study SHP647-301 or SHP647-302.
2. Subjects who permanently discontinued investigational product because of an
adverse event, regardless of relatedness to investigational product, in
induction study SHP647-301 or SHP647-302.
3. Subjects who are likely to require surgery for UC during the study period.
4. Subjects are females who became pregnant during induction study SHP647-301
or SHP647-302, females who are planning to become pregnant during the study
period, or males or females of childbearing potential not agreeing to continue
appropriate contraception methods (ie, highly effective methods for female and
medically appropriate methods for male study subjects) through the conclusion
of study participation.
5. Subjects who do not agree to postpone donation of any organ or tissue,
including male subjects who are planning to bank or donate sperm, and female
subjects who are planning to harvest or donate eggs, for the duration of the
study and through 16 weeks after last dose of investigational product.
6. Subjects who, in the opinion of the investigator or the sponsor, will be
uncooperative or unable to comply with study procedures.
7. Subjects who have a newly diagnosed malignancy or recurrence of malignancy
(other than resected cutaneous basal cell carcinoma, squamous cell carcinoma,
or carcinoma in situ of the uterine cervix that has been treated with no
evidence of recurrence).
8. Subjects who have developed any major illness/condition or evidence of an
unstable clinical condition (eg, renal, hepatic, hematologic, gastrointestinal
(except disease under study), endocrine, cardiovascular, pulmonary, immunologic
[eg, Felty*s syndrome], or local active infection/infectious illness) that, in
the investigator*s judgment, will substantially increase the risk to the
subject if he or she participates in the study.
9. Subjects with any other severe acute or chronic medical or psychiatric
condition or laboratory or electrocardiogram (ECG) abnormality that may
increase the risk associated with study participation or investigational
product administration or may interfere with the interpretation of study
results and, in the judgment of the investigator, would make the subject
inappropriate for entry into this study.
10. Subjects with known exposure to Mycobacterium tuberculosis (TB) since
testing at screening in induction study SHP647-301 or SHP647-302 and who are
without a generally accepted course of treatment.
11. Subjects who are investigational site staff members or relatives of those
site staff members or subjects who are sponsor employees directly involved in
the conduct of the study.
12. Subjects who are participating in or plan to participate in other
investigational studies (other than induction study SHP647-301 or SHP647-302)
during study SHP647-303.
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 | EUCTR2017-000573-37-NL |
| ClinicalTrials.gov | NCT03290781 |
| CCMO | NL62886.028.17 |