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 form of inflammatory bowel disease (IBD) that causes inflammation and ulcers in the colon resulting in abdominal pain and bloody diarrhea. |
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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 |
1. To assess the safety and tolerability of PRA023 following 12-weeks of induction therapy 2. To compare the efficacy of PRA023 vs placebo for induction of clinical remission at Week 12
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E.2.2 | Secondary objectives of the trial |
Compare the efficacy of PRA023 vs placebo for induction of: - endoscopic improvement - clinical response - histologic remission - histologic-endoscopic mucosal improvement - mucosal healing
Compare the efficacy of PRA023 vs placebo for change in IBDQ
Compare the efficacy of PRA023 vs placebo in subjects who are companion diagnostic positive (CDx+) for induction of: - clinical remission - endoscopic improvement - clinical response - histologic remission - histologic-endoscopic mucosal improvement - mucosal healing Compare the efficacy of PRA023 vs placebo in subjects who are CDx+ per alternative algorithm for clinical remission at Week 12
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Title: Pharmacokinetic Sub-Study Date and Version: 18 June 2021, V2.0 Objective: To better understand the PK of PRA023 in subjects with UC and to evaluate the PK of PRA023 at steady state |
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E.3 | Principal inclusion criteria |
Subjects are required to meet the following criteria in order to be included in the study: - Male or female ≥18 years of age - Subjects must have had a documented diagnosis of UC to be eligible for study participation. - Moderately to severely active UC - Subjects must have had insufficient response and/or intolerance to conventional therapy - For subjects who are women of childbearing potential (WOCBP) involved in any sexual intercourse that could lead to pregnancy, the subject has used two highly effective methods of contraception for at least 4 weeks prior to Day 1 and agrees to continue to use two highly effective methods of contraception until at least 12 weeks after the last dose of study drug - Male subjects must use, with their female partner of childbearing potential, two highly effective methods of contraception and refrain from sperm donation from screening to 12 weeks after the last dose of study drug - Subject must meet concomitant medication stabilization requirements, as applicable - Able to provide written informed consent and understand and comply with the requirements of the study
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E.4 | Principal exclusion criteria |
- WOCBP and men with WOCBP partner unwilling/ unable to use two highly effective methods of contraception - Women who are pregnant or breastfeeding - Women with a positive pregnancy test - Diagnosis of Crohn's disease or indeterminate colitis - UC limited to the rectum (<15 cm from anal verge) - Current evidence of fulminant colitis, toxic megacolon, or bowel perforation - Current or impending need for colostomy or ileostomy - Previous total proctocolectomy or partial colectomy - Surgical bowel resection within 3 months before screening - Concomitant primary sclerosing cholangitis (PSC) - Past or current evidence of colonic dysplasia that has not been completely removed - Scheduled or anticipate the need for surgery, except dermatologic procedures - History of clinically significant drug or alcohol abuse - Prior exposure to PRA023 - Prisoners or subjects who are compulsorily detained for treatment of either a psychiatric or physical illness must not be enrolled into this study - Legal or mental incapacitation, or inability to understand and comply with the requirements of the study
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E.5 End points |
E.5.1 | Primary end point(s) |
1. The proportion of subjects reporting adverse events (AEs), serious adverse events (SAEs), AEs leading to discontinuation, and markedly abnormal laboratory values. 2. The proportion of subjects in clinical remission at Week 12.
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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) |
1. The proportion of subjects with endoscopic improvement at Week 12. 2. The proportion of subjects in clinical response at Week 12. 3. The proportion of CDx+ subjects in clinical remission. 4. The proportion of subjects with histologic remission at Week 12. 5. The proportion of subjects with histologic-endoscopic mucosal improvement at Week 12. 6. The proportion of CDx+ subjects with endoscopic improvement at Week 12. 7. The proportion of CDx+ subjects in clinical response at Week 12. 8. The proportion of CDx+ subjects with histologic remission at Week 12. 9. The proportion of CDx+ subjects with histologic-endoscopic mucosal improvement at Week 12. 10. The proportion of CDx+ subjects with clinical remission Week 12. 11. The proportion of subjects with mucosal healing at Week 12. 12. The proportion of CDx+ subjects with mucosal healing at Week 12. 13. The proportion of subjects with IBDQ response at Week 12. 14. The proportion of CDx+ subjects with IBDQ response at Week 12. 15. The proportion of CDx+ subjects (per alternative algorithm) in clinical remission at Week 12.
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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 | 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 | Yes |
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) | 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 | 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 | No |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 23 |
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 |
Australia |
Canada |
Georgia |
Israel |
Russian Federation |
Ukraine |
United States |
Belgium |
France |
Hungary |
Italy |
Poland |
United Kingdom |
Czechia |
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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 | 3 |
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 | 6 |
E.8.9.2 | In all countries concerned by the trial days | 15 |