E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Ulcerative colitis or Crohn's Disease |
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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 or long-term condition that results in inflammation of the the gastrointestinal tract. |
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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 | 10017947 - Gastrointestinal disorders |
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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 |
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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 safety and tolerability of long-term treatment with ontamalimab in subjects with moderate to severe UC or CD. |
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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. |
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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. |
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E.4 | Principal exclusion criteria |
Subjects with UC: 1. Subjects who had major protocol deviation(s) (as determined by the sponsor) in Study SHP647-301, SHP647-302, or SHP647-303. 2. Subjects who permanently discontinued investigational product because of an adverse event (AE), regardless of relatedness to investigational product, in Study SHP647-301, SHP647-302, or SHP647303. 3. Subjects who are likely to require major surgery for UC. 4. Subjects are females who became pregnant during Study SHP647-301, SHP647-302, or SHP647-303, 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 (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 [GI] [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 Study SHP647-301 or SHP647-302 and who have been advised to require treatment for latent or active disease, but 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 other investigational studies (other than SHP647-301, SHP647-302, or SHP647-303) or plan to participate in other investigational studies during long-term extension study SHP647304.
Subjects with CD: 1. Subjects who had major protocol deviation(s) (as determined by the sponsor) in Study SHP647-305, SHP647-306, or SHP647-307. 2. Subjects who permanently discontinued investigational product because of an AE, regardless of relatedness to investigational product, in Study SHP647-305, SHP647-306, or SHP647-307. 3. Subjects who are likely to require major surgery for CD or developed acute severe complications of CD (with or without fulfilling the treatment failure criteria in the maintenance study) that required immediate intervention (eg, need for immediate biologic treatment with proven effect) and/or CDAI score >450. 4. Subjects are females who became pregnant during Study SHP647-305, SHP647-306, or SHP647-307, 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.,6.,7.,8.,9. - The same as for the subjects with UC 10. Subjects with known exposure to TB since testing at screening in Study SHP647-305 or SHP647-306, and who have been advised to require treatment for latent or active disease, but 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 other investigational studies (other than SHP647-305, SHP647-306, or SHP647-307) or plan to participate in other investigational studies during long-term extension study SHP647-304. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the assessment of safety as measured by: incidence and severity of AEs; incidence and nature of serious infections; and actual values and change from baseline, as well as incidence of abnormalities, in laboratory tests, ECGs, and vital signs. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Please refer to section “Study Schedules” of the Protocol |
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E.5.2 | Secondary end point(s) |
Secondary Endpoints – Subjects with Ulcerative Colitis: The secondary endpoint is 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 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. |
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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. |
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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 | 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 |
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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 | 30 |
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 |
Colombia |
New Zealand |
Switzerland |
Bosnia and Herzegovina |
Ukraine |
Australia |
Brazil |
Canada |
Israel |
Japan |
Korea, Republic of |
Lebanon |
Mexico |
Russian Federation |
Serbia |
South Africa |
Turkey |
United Kingdom |
United States |
Austria |
Belgium |
Bulgaria |
Croatia |
Czechia |
Estonia |
France |
Germany |
Greece |
Hungary |
Ireland |
Italy |
Lithuania |
Netherlands |
Poland |
Portugal |
Romania |
Slovakia |
Spain |
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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 | 10 |
E.8.9.1 | In the Member State concerned days | 25 |
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 |