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 |
Crohn's disease is a form of inflammatory bowel disease (IBD) that causes inflammation of the digestive tract 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 | 20.0 |
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 |
1. To evaluate the safety and tolerability of PRA023 following 12-weeks of induction therapy 2. To assess the proportion of subjects with endoscopic improvement at Week 12
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E.2.2 | Secondary objectives of the trial |
To assess the proportion of subjects with: - Clinical remission at Week 12 - Endoscopy and clinical improvement at Week 12 - Biomarker and clinical improvement at Week 12 - Normalization of hsCRP at Week 12, among subjects with elevated concentrations at Baseline - Normalization of fecal calprotectin at Week 12, among subjects with elevated concentrations at Baseline - Clinical improvement at Week 12 - Two-component patient-reported outcome remission at Week 12 To assess: - The change in SES-CD score from Baseline to Week 12 - The PK of PRA023 - The immunogenicity of PRA023 |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Male or female ≥ 18 years of age. - A documented diagnosis of CD. - Moderately to severely active CD as defined by CDAI of ≥ 220 and ≤ 450. - SES-CD score ≥ 6 if ileocolonic or colonic disease; or ≥ 4 if isolated ileal disease only. - Subjects must have had insufficient response and/or intolerance to conventional therapy. |
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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 on enrollment or prior to Day 1 - Diagnosis of ulcerative colitis or indeterminate colitis - CD isolated to the stomach, duodenum, jejunum, or perianal region, without colonic and/or ileal involvement - Suspected or diagnosed intra-abdominal or perianal abscess at Screening - Known symptomatic stricture or stenosis not passable in endoscopy (including pediatric colonoscope) - Current stoma or need for colostomy or ileostomy - Previous small bowel resection with combined resected length of > 100cm or previous colonic resection of > 2 segments - Currently receiving total parenteral nutrition - Surgical bowel resection within 3 months before screening - Concomitant PSC - Prior exposure to PRA023 - Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious disease) illness - 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. Safety and tolerability: the proportion of subjects reporting AEs, SAEs, AEs leading to discontinuation, and markedly abnormal laboratory values 2. The proportion of subjects with endoscopic improvement, 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 in clinical remission at Week 12 2. The proportion of subjects with endoscopic and clinical improvement AND reduction in CDAI ≥ 100 points from Baseline at Week 12 3. The proportion of subjects with both biomarker and clinical improvement at Week 12 4. The proportion of subjects with normalization of hsCRP, among subjects with elevated concentrations at Baseline, at Week 12 5. The proportion of subjects with normalization of fecal calprotectin (as defined by fecal calprotectin < ULN), among subjects with elevated concentrations at Baseline, at Week 12 6. The proportion of subjects in clinical response at Week 12 7. The proportion of subjects with PRO-2 remission at Week 12 8. Change in SES-CD score at Week 12 from Baseline 9. Descriptive summaries of PK and immunogenicity of PRA023 10. Proportion of subjects developing anti-drug antibody (ADA) and neutralizing antibody (Nab) |
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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 | 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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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 | No |
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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 20 |
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 |
Poland |
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 | 3 |
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 | 8 |