E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Ulcerative colitis or Crohn's Disease |
|
E.1.1.1 | Medical condition in easily understood language |
Long-term condition that results in inflammation and ulcers of the colon and rectum or long-term condition that results in inflammation of the gastrointestinal tract. |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Digestive System Diseases [C06] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10045365 |
E.1.2 | Term | Ulcerative colitis |
E.1.2 | System Organ Class | 10017947 - Gastrointestinal disorders |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10011401 |
E.1.2 | Term | Crohn's disease |
E.1.2 | System Organ Class | 10017947 - Gastrointestinal disorders |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of the study is to evaluate the safety and tolerability of long-term treatment with ontamalimab in subjects with moderate to severe ulcerative colitis (UC) or Crohn's disease (CD). |
|
E.2.2 | Secondary objectives of the trial |
Secondary - Subjects with Ulcerative Colitis:
To evaluate the maintenance of response to long-term treatment with
ontamalimab as measured by clinical composite score and biomarkers,
with or without endoscopy.
Secondary - Subjects with Crohn's Disease:
To evaluate the maintenance of response to long-term treatment with
ontamalimab as measured by Crohn's Disease Activity Index (CDAI)
score and biomarkers, with or without endoscopy.
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Subjects with UC:
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, as applicable, to participate in the study.
3. Subjects must have been enrolled previously in Study SHP647-301 or
SHP647-302 and are in the treatment period of Study SHP647-303,
completed the ET or Week 52 visit in the maintenance study SHP647-303, had responded to ontamalimab treatment (in the induction and/or
maintenance studies), and meet one of the following criteria:
o Subjects are on placebo at the maintenance study ET or Week 52 visit:
they received ontamalimab in the induction studies and fulfilled the
maintenance study response entry criteria, OR
o Subjects have received ontamalimab at the maintenance study ET or
Week 52 visit:
Clinical composite score that has decreased by ≥2 points and ≥30%,
with an accompanying decrease in the subscore for RB ≥1 point or a
subscore for RB ≤1, compared to the baseline value for induction
studies, AND/OR
Composite score that has decreased by ≥30% and ≥3 points compared
to the baseline value for induction studies.
4. Subjects receiving any treatment(s) for UC described in Section 5.2.1
are eligible provided they have been on a
stable dose for the designated period of time.
Subjects with Crohn's Disease
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, as applicable, to participate in the study.
3. Subjects must have been enrolled previously in Study SHP647-305 or
SHP647-306 and are in the treatment period of Study SHP647-307,
completed the ET or Week 52 visit in maintenance study SHP647-307,
had responded to ontamalimab treatment (in the induction and/or
maintenance studies), and meet one of the following criteria:
o Subjects are on placebo at the maintenance study ET or Week 52 visit:
they received ontamalimab in the induction study and fulfilled the
maintenance study response criteria, OR
o Subjects have received ontamalimab at the maintenance study ET or
Week 52 visit:
• CDAI score that has decreased by ≥100 points at the end of treatment
visit compared to the baseline value for induction studies, AND/OR
• SES-CD that has decreased by ≥25% compared to the baseline value
for induction studies.
4. Subjects receiving any treatment(s) for CD described in Section 5.3.1
are eligible provided they have been on a
stable dose for the designated period of time. |
|
E.4 | Principal exclusion criteria |
Subjects with UC Entering from an Induction or Maintenance
Study/Subjects with CD
1. Subjects who had major protocol deviation(s) (as determined by the
sponsor) in previous studies.
2. Subjects who permanently discontinued investigational product
because of an AE, regardless of relatedness to investigational product, in
previous studies.
3. Subjects who are likely to require major surgery for UC/CD.
4. Subjects are females who became pregnant during the previous
UC/CD studies, females who are lactating, females who are planning to
become pregnant during the study period, or males or females of
childbearing potential not agreeing to continue using 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
8. Subjects who have developed any major illness/condition or evidence
of an unstable clinical condition (except disease under study) 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 М.tuberculosis (TB) since testing at
screening in previous UC/CD studies and who have been advised to
require treatment for latent or active disease, but who are without a
generally accepted course of treatment.
Subjects with UC Entering directly
1. Subjects with indeterminate colitis, microscopic colitis, nonsteroidal
anti-inflammatory drug-induced colitis,
ischemic colitis, infectious colitis, or clinical/histologic findings
suggestive of CD.
2. Subjects with colonic dysplasia or neoplasia.
3. Subjects with past medical history or presence of toxic megacolon.
4. Subjects with colonic stricture, past medical history of colonic
resection, a history of bowel surgery within 6
months before screening, or who are likely to require surgery for UC
during the treatment period.
5. Subjects at risk for colorectal cancer must have a colonoscopy (Eaden
and Mayberry, 2002) performed during the
screening period with results available within 10 days before the
baseline visit (Visit 1), unless the subject has
had a surveillance colonoscopy performed within 1 year prior to
screening, and any adenomatous polyps found at
that examination have been excised. 6. Subjects with known or
suspected intolerance or hypersensitivity to the investigational
product(s), closely related compounds, or any of the stated ingredients.
7. Subjects have received anti-TNF treatment within 60 days or
vedolizumab within 120 days before baseline
8. Subjects have received any biologic with immunomodulatory
properties (other than anti-TNFs) within 90 days
before baseline
9. Subjects have received any nonbiologic treatment with
immunomodulatory properties within 30 days before baseline.
10. Subjects have ever received anti-integrin/adhesion molecule
treatment (eg, natalizumab, efalizumab,
etrolizumab, or any other investigational anti-integrin/adhesion
molecule) with the exception of vedolizumab.
11. Subjects have received parenteral or rectal glucocorticoids, or rectal
5-ASA, within 14 days before screening
endoscopic procedure.
12. Subjects have received leukocyte apheresis or selective lymphocyte,
monocyte, or granulocyte apheresis or
plasma exchange within 30 days before baseline
13. Subjects have participated in other investigational studies within
either 30 days or 5 half-lives of investigational
product used in the study before baseline
14. Subjects have received a live (attenuated) vaccine within 30 days
before the baseline
15. Subjects with active enteric infections, Clostridium difficile infection
or pseudomembranous colitis, evidence of active cytomegalovirus
infection or Listeria monocytogenes, known active invasive fungal
infections, clinically significant underlying disease that could predispose
the subjects to infections, or a history of serious infection within 4
weeks before the baseline |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is safety assessment as is assessment of safety as measured by: incidence and severity of AEs; incidence and nature of serious infections; actual values and change from baseline, as well as the incidence of abnormalities, in laboratory tests, ECGs, and vital signs; and antidrug antibodies. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Please refer to section “Study Schedules” of the Protocol |
|
E.5.2 | Secondary end point(s) |
Secondary Efficacy Endpoints – Subjects with Ulcerative Colitis:
The secondary efficacy endpoints are as follows:
• Treatment response over time, with response defined as clinical composite score that has decreased by ≥2 points and ≥30%, with an
accompanying decrease in the subscore for RB ≥1 point or a subscore for RB ≥1 , and/or composite score that has decreased by ≥30% and ≥3 points compared to the baseline value for induction studies.
Secondary Efficacy Endpoints – Subjects with Crohn's Disease:
The secondary endpoint is as follows:
• Treatment response over time, with response defined as CDAI score that has decreased by ≥100 points compared to the baseline value for
induction studies and/or SES-CD that has decreased by ≥25% compared to the baseline value for induction studies. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Secondary endpoints will be summarized by treatment group using descriptive statistics at each assessment visit. |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
|
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 364 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Argentina |
Australia |
Brazil |
Canada |
Colombia |
Israel |
Japan |
Korea, Republic of |
Lebanon |
Mexico |
New Zealand |
South Africa |
United States |
Austria |
Estonia |
France |
Lithuania |
Poland |
Bulgaria |
Netherlands |
Romania |
Spain |
Switzerland |
Czechia |
Germany |
Greece |
Italy |
Belgium |
Bosnia and Herzegovina |
Croatia |
Hungary |
Ireland |
Portugal |
Russian Federation |
Slovakia |
Turkey |
Ukraine |
United Kingdom |
Serbia |
|
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
The Study Completion Date is defined as the date the final subject, across all sites, completes their final protocol-defined assessment. Please note that this includes the follow-up visit or contact, whichever is later. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 8 |
E.8.9.1 | In the Member State concerned months | 11 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 10 |
E.8.9.2 | In all countries concerned by the trial days | 25 |