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 |
Ulcerative Colitis is a type of inflammatory bowel disease that causes the lining of the large intestine (colon) to become inflamed (irritated and swollen) which may cause ulcers and bleeding. |
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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 |
- To compare the efficacy of brazikumab with that of placebo to achieve clinical remission |
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E.2.2 | Secondary objectives of the trial |
- To compare the efficacy of brazikumab with that of placebo to achieve sustained clinical remission
- To compare the efficacy of brazikumab with that of placebo to achieve corticosteroid-free (CS-free) clinical remission
- To evaluate the pharmacokinetics (PK) and immunogenicity of brazikumab in participants with UC
- To characterize the exposure-response relationships of brazikumab
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Ability to provide written informed consent prior to any study procedures and willing and able to attend all study visits, comply with the study procedures, read and write in order to complete questionnaires, and be able to complete the study period.
2. Aged 18 to 80 years of age, inclusive, at screening.
3. Diagnosis of UC with an onset of symptoms for a minimum of 3 months prior to screening as determined by the investigator based on clinical history, exclusion of infectious causes, and characteristic endoscopic and histologic findings.
4. Evidence of UC extending proximal to the rectum (≥ 15 cm of involved colon).
5. Moderately to severely active UC as defined by Stool Frequency and Rectal Bleeding subscores and Modified Mayo endoscopic subscore.
6. Participant had an inadequate, failed response, or intolerance to intervention with oral aminosalicylates, oral corticosteroids, azathioprine, methotrexate, or 6- mercaptopurine, or demonstrated corticosteroid dependence for the treatment of ulcerative colitis.
7. Females of childbearing potential who are sexually active with a nonsterilized male partner must use 2 acceptable methods of contraception.
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E.4 | Principal exclusion criteria |
1. Participant has UC limited to the rectum (ie, not beyond 15 cm of the anal verge)
2. History of fulminant colitis, a diagnosis of Crohn’s disease or indeterminate colitis, presence or history of a fistula consistent with Crohn’s disease, primary sclerosing cholangitis, celiac disease, or bile acid malabsorption. Participants with a history of toxic megacolon within 12 months of screening.
3. History of subtotal colectomy with ileorectostomy or colectomy with ileonal pouch, Koch pouch, ileostomy, or other prior colonic resection, or need for surgical intervention for control of UC anticipated within 6 months.
4. Participant has received the following treatment:
- Infliximab: within 8 weeks prior to Baseline (Visit 2)
- Adalimumab, certolizumab pegol, or golimumab: within 10 weeks prior to Baseline (Visit 2)
- Vedolizumab within 18 weeks prior to Baseline (Visit 2)
- Other prohibited medication, biologic or small molecule treatment within 5 half-lives prior to Baseline (Visit 2)
5. Participant has previously received vedolizumab, and was intolerant to intervention or
had met the criteria for primary or secondary non-response to intervention.
19. Participant is pregnant, breastfeeding, or plans to become pregnant during the study.
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E.5 End points |
E.5.1 | Primary end point(s) |
Clinical remission:
- modified Mayo Score (mMS) at Week 10:
Endoscopy subscore = 0 or 1, AND
Rectal bleeding subscore = 0, AND
Stool frequency subscore = 0 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Mayo score items:
Stool frequency - Visit 1 through Follow-up 2 (e-diary)
Rectal bleeding - Visit 1 through Follow-up 2 (e-diary)
Findings of endoscopy - Visits 1, 6, 17
Physician’s global assessment - Visits 1, 6, 17
Each individual item assessed on 0-3 ordinal scale described in Mayo Scoring System for Assessment of Ulcerative Colitis Activity. |
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E.5.2 | Secondary end point(s) |
1. Sustained clinical remission:
- mMS at both Week 10 and Week 54:
Endoscopy subscore = 0 or 1, AND
Rectal bleeding subscore = 0, AND
Stool frequency subscore = 0
2. CS-free clinical remission:
- mMS at Week 54 for participants who are CS-free for at least the last 12 weeks before the assessment at Week 54:
Endoscopy subscore = 0 or 1, AND
Rectal bleeding subscore = 0, AND
Stool frequency subscore = 0
3. Population PK model of serum concentrations of brazikumab and analysis for serum anti-brazikumab antibodies
4. Exposure-response model linking primary endpoints to metrics of model-predicted individual
brazikumab exposures |
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
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.6.13.1 | Other scope of the trial description |
Blood and stool samples will be collected and analyzed to evaluate protein, nucleic acid, and
cellular biomarkers, optional blood sample for genetic research |
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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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | Yes |
E.8.1.7.1 | Other trial design description |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 5 |
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 | 7 |
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 |
Australia |
Belgium |
Brazil |
Bulgaria |
Canada |
China |
Colombia |
Czech Republic |
France |
Germany |
Hungary |
India |
Israel |
Italy |
Japan |
Korea, Republic of |
Malaysia |
Mexico |
Poland |
Romania |
Russian Federation |
Singapore |
South Africa |
Spain |
Switzerland |
Taiwan |
Turkey |
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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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 | 4 |
E.8.9.1 | In the Member State concerned days | 15 |
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 | 4 |
E.8.9.2 | In all countries concerned by the trial days | 15 |