E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Long-term condition that results in inflammation and ulcers of the colon and rectum |
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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 | 100000004856 |
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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 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 UC. |
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E.2.2 | Secondary objectives of the trial |
The key secondary objectives of the study are as follows:
• 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. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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, as applicable, 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 are eligible provided they have been, and are anticipated to be, on a stable dose for the designated period of time. |
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E.4 | Principal exclusion criteria |
Subjects are excluded from the study if any of the following exclusion 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(AE), 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 or 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 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.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is proportion of subjects in remission at the Week 52 visit. Remission is defined as a composite score of patient-reported symptoms using daily e-diary and centrally read endoscopy as follows:
• stool frequency subscore of 0 or 1 with at least a 1-point change from induction (SHP647 301 or SHP647 302) baseline
AND
• rectal bleeding subscore of 0
AND
• endoscopic subscore of 0 or 1 (modified, excludes friability). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
The key secondary efficacy endpoints are as follows:
• Endoscopic remission, as defined by centrally read endoscopic subscore 0 or 1 (modified, excludes friability), at the Week 52 visit.
• Clinical remission as defined by stool frequency subscore of 0 or 1 with at least a 1-point change from induction study (SHP647-301 or SHP647-302) baseline in stool frequency subscore, and rectal bleeding subscore of 0, at the Week 52 visit.
• Sustained remission, ie, in remission at the SHP647-303 Week 52 visit, among subjects who were in remission at the time of baseline in study SHP647 303. Remission is defined as a composite score of patient-reported symptoms using daily e-diary and centrally read endoscopy, with stool frequency subscore of 0 or 1 with at least a 1-point change from induction study (SHP647-301 or SHP647-302) baseline, and rectal bleeding subscore of 0, and endoscopic subscore of 0 or 1 (modified, excludes friability).
• Clinical response based on composite score at the Week 52 visit. Clinical response (composite) is defined as a decrease from induction study (SHP647-301 or SHP647 302) baseline in the composite score of subject-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.
• Mucosal healing, based on endoscopic and histologic assessment, at the Week 52 visit. Mucosal healing is defined by centrally read endoscopic subscore 0 or 1 (modified, excludes friability) and centrally read Geboes score of ≤2.
• Glucocorticoid-free clinical remission at Week 52, among subjects using glucocorticoids in study SHP647-303 baseline. Glucocorticoid-free clinical remission is defined as clinical remission in addition to not requiring any treatment with glucocorticoids for at least 4 weeks prior to the Week 52 visit. Clinical remission is defined as stool frequency subscore of 0 or 1 with at least a 1-point change from induction study (SHP647-301 or SHP647-302) baseline in stool frequency subscore, and rectal bleeding subscore of 0, at the Week 52 visit.
• Glucocorticoid-free remission at Week 52, among subjects using glucocorticoids in study SHP647-303 baseline. Glucocorticoid-free remission is defined as remission in addition to not requiring any treatment with glucocorticoids for at least 4 weeks prior to the Week 52 visit. Remission is defined as a composite score of subject-reported symptoms using daily e diary and endoscopy, with stool frequency subscore of 0 or 1 with at least a 1-point change from induction study (SHP647-301 or SHP647-302) baseline, and rectal bleeding subscore of 0, and endoscopic subscore of 0 or 1 (modified, excludes friability). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | Yes |
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 | Yes |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
25 mg or 75 mg ontamalimab |
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E.8.2.4 | Number of treatment arms in the trial | 3 |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 337 |
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 |
Austria |
Belgium |
Bosnia and Herzegovina |
Brazil |
Bulgaria |
Canada |
Colombia |
Croatia |
Czechia |
France |
Germany |
Greece |
Hungary |
Ireland |
Israel |
Italy |
Japan |
Korea, Republic of |
Lebanon |
Lithuania |
Mexico |
Netherlands |
New Zealand |
Poland |
Portugal |
Romania |
Russian Federation |
Serbia |
Slovakia |
South Africa |
Spain |
Switzerland |
Turkey |
Ukraine |
United Kingdom |
United States |
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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
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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. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 7 |
E.8.9.2 | In all countries concerned by the trial days | 26 |