| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| E.1.1.1 | Medical condition in easily understood language |
| Long-term condition that results in inflammation and ulcers of the colon and rectum |
|
| 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 |
|
| 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 in inducing remission,based on composite score of patient-reported symptoms and centrally read endoscopy, in subjects with moderate to severe ulcerative colitis (UC). |
|
| E.2.2 | Secondary objectives of the trial |
To evaluate the efficacy of ontamalimab in achieving endoscopic remission, based on centrally read endoscopy.
• To evaluate the efficacy of ontamalimab in achieving clinical remission, based on composite score of patient-reported symptoms.
• To evaluate the efficacy of ontamalimab in inducing clinical response, based on composite score of patient-reported symptoms and centrally read endoscopy.
• To evaluate the efficacy of ontamalimab in achieving mucosal healing, based on endoscopic and histological assessment using the Geboes Score grading system. |
|
| 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 must be between ≥16 and ≤80 years of age at the time of the signing of the informed consent/assent form.
Note: Subjects <18 years of age must weigh ≥40 kg and must have body mass index (BMI) ≥16.5 kg/m2
2. Subjects must have a documented diagnosis (radiologic or endoscopic with histology) of UC for ≥3 months before screening. The following must be available in each subject’s source documentation:
• A biopsy report to confirm the histological diagnosis.
• A report documenting disease duration based upon prior colonoscopy.
Note: If this documentation is not available at the time of screening, a colonoscopy with biopsy to confirm the diagnosis is required during the screening period.
3. Subjects must be willing to undergo a flexible sigmoidoscopy or colonoscopy (if preferred), including biopsy sample collection, during screening after all other inclusion criteria have been met.
4. Subjects must have moderate to severe active UC, defined as a total Mayo score of ≥6, including a centrally read endoscopic subscore ≥2, rectal bleeding subscore ≥1, and stool frequency subscore ≥1 at baseline (Visit 2).
5. Subjects must have evidence of UC extending proximal to the rectum (ie, not limited to proctitis).
6. Subjects must have had an inadequate response to, or lost response to, at least 1 conventional treatment such as mesalamine (5 aminosalicylic acid [5-ASA]), glucocorticoids, immunosuppressants (azathioprine [AZA], 6 mercaptopurine [6 MP], or methotrexate [MTX]), or anti-TNF.
7. Subjects must have evidence of UC extending proximal to the rectum (ie, not limited to proctitis).
8. Subjects must have had an inadequate response to, or lost response to, or had an intolerance to at least 1
conventional treatment such as mesalamine (5-aminosalicylic acid [5-ASA]), glucocorticoids,
immunosuppressants (azathioprine, 6-mercaptopurine, or methotrexate), or anti-TNF
9. 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.
10. Subjects are males or nonpregnant, nonlactating females who, if sexually active, agree to comply with the
contraceptive requirements of the protocol, or females of nonchildbearing potential. Males and females of
reproductive potential who are sexually active must agree to use appropriate contraception (ie, highly effective methods for female and medically appropriate methods for male study subjects) (as described in Section 4.4 of the protocol) for the duration of the study. |
|
| E.4 | Principal exclusion criteria |
Subjects are excluded from the study if any of the following exclusion criteria are met:
1. Subjects with indeterminate colitis, microscopic colitis, non-steroidal anti-inflammatory drug-induced colitis, ischemic colitis, infectious colitis, or clinical/histologic findings suggestive of Crohn’s disease.
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 2), 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. Colonoscopy report and pathology report (if biopsies are obtained) from the
colonoscopy performed during screening or in the prior year confirming no evidence of dysplasia and colon
cancer must be available in the source documents.
Subjects at risk for colorectal cancer include, but are not limited to:
Subjects with extensive colitis for ≥8 years or disease limited to left side of colon (ie, distal to splenic
flexure) for ≥10 years before screening, regardless of age.
Subjects ≥50 years of age at the time of signing of the informed consent form.
6. Subjects have had prior treatment with ontamalimab (formerly PF-00547659; SHP647).
7. Subjects with known or suspected intolerance or hypersensitivity to the investigational product(s), closely
related compounds, or any of the stated ingredients.
8. Subjects have received anti-TNF treatment within 60 days before baseline (Visit 2).
9. Subjects have received any biologic with immunomodulatory properties (other than anti-TNFs) within 90 days before baseline (Visit 2).
10. Subjects have received any nonbiologic treatment with immunomodulatory properties (other than their current
background UC treatment) within 30 days before baseline (Visit 2).
11. Subjects have ever received anti-integrin/adhesion molecule treatment (eg, natalizumab, vedolizumab,
efalizumab, etrolizumab, or any other investigational anti-integrin/adhesion molecule).
12. Subjects have received parenteral or rectal glucocorticoids, or rectal 5-ASA, within 14 days before screening
endoscopic procedure.
13. Subjects have received leukocyte apheresis or selective lymphocyte, monocyte, or granulocyte apheresis or
plasma exchange within 30 days before baseline (Visit 2).
14. Subjects have participated in other investigational studies within either 30 days or 5 half-lives of
investigational product used in the study (whichever is longer) before baseline (Visit 2).
15. Subjects have received a live (attenuated) vaccine within 30 days before the baseline visit (Visit 2).
16. Subjects with active enteric infections (positive stool culture and sensitivity), Clostridium difficile infection or pseudomembranous colitis [subjects with C. difficile infection at screening may be allowed re-test after
treatment], evidence of active cytomegalovirus infection or Listeria monocytogenes, known active invasive
fungal infections such as histoplasmosis or parasitic infections, clinically significant underlying disease that
could predispose the subjects to infections, or a history of serious infection (requiring parenteral antibiotic
and/or hospitalization) within 4 weeks before the baseline visit (Visit 2).
17. Subjects with abnormal chest x-ray findings at screening (Visit 1), such as presence of active tuberculosis
(TB), general infections, heart failure, or malignancy. (A chest x-ray performed up to 12 weeks before study
entry [screening, Visit 1] may be used if available; documentation of the official reading must be located and
available in the source documentation.) |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
The primary efficacy endpoint is remission at the Week 12 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 baseline
AND
• rectal bleeding subscore of 0
AND
• endoscopic subscore of 0 or 1 (modified, excludes friability). |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
• Endoscopic remission, as defined by centrally read endoscopic subscore 0 or 1 (modified, excludes friability), at the Week 12 visit.
• Clinical remission, as defined by stool frequency subscore of 0 or 1 with at least a 1-point change from baseline in stool frequency subscore, and rectal bleeding subscore of 0, at the Week 12 visit.
• Clinical response based on composite score at the Week 12 visit. Clinical response (composite) is defined as a decrease from 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.
• Mucosal healing based on endoscopic and histological assessment at the Week 12 visit. Mucosal healing is defined by centrally read endoscopic subscore 0 or 1 (modified, excludes friability) and centrally read Geboes score of ≤2.
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
| 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 | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| 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.6.13.1 | Other scope of the trial description |
|
| 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 |
|
| 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 | 3 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 140 |
| 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 |
| Belgium |
| Bosnia and Herzegovina |
| Bulgaria |
| Canada |
| Colombia |
| Estonia |
| France |
| Greece |
| Hungary |
| Ireland |
| Japan |
| Korea, Republic of |
| Lebanon |
| Mexico |
| Portugal |
| Slovakia |
| Spain |
| Switzerland |
| Turkey |
| Ukraine |
| United States |
|
| 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 | 2 |
| E.8.9.1 | In the Member State concerned months | 9 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 9 |
| E.8.9.2 | In all countries concerned by the trial days | 19 |
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