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 |
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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.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Main Objectives: - To evaluate the long-term safety of RPC1063 for the treatment of all patients with moderate to severe ulcerative colitits - To evaluate the long-term efficacy of RPC1063 for the treatment of adult patients with moderate to severe ulcerative colitits
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Previously participated in a trial of RPC1063 (eg. RPC01-3101 for completed at least 1 year of the open-label period of RPC01-202) and meet the criteria for participation in the open label extension as outlined in the prior trial 2. Females patients of childbearing potential (FCBP): Must agree to practice a highly effective method of contraception throughout the trial until completion of the 90-day safety follow-up visit. Highly effective methods of contraception are those that alone or in combination result in a failure rate of a Pearl index of less than 1% per year when used consistently and correctly. Acceptable methods of birth control in the trial are the following: -combined hormonal (oestrogen and progestogen containing) contraception, which may be oral, intravaginal, or transdermal -progestogen-only hormonal contraception associated with inhibition of ovulation, which may be oral, injectable, or implantable -placement of an intrauterine device (IUD) -placement of an intrauterine hormone-releasing system (IUS) -bilateral tubal occlusion -vasectomized partner - complete sexual abstinence Periodic abstinence (calendar, symptothermal, post-ovulation methods), withdrawal (coitus interruptus), spermicides only, and lactational amenorrhea method are not acceptable methods of contraception. 3. Must provide written informed consent prior to any trial related procedures and have the ability to be compliant with the schedule of protocol assessments.
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E.4 | Principal exclusion criteria |
Exclusions Related to Medications: 1. Have received any of the following therapies since the first dose of investigational drug in the prior RPC1063 trial: • Treatment with a biologic agent • Treatment with an investigational agent other than RPC1063 • Treatment with a live vaccine or live attenuated vaccine within 4 weeks prior to Visit 1 of this trial • Treatment with D-penicillamine, leflunomide, thalidomide, natalizumab, fingolimod, etrasimod, or tofacitinib • Treatment with lymphocyte-depleting therapies (e.g., Campath, anti-CD4, cladribine, rituximab, ocrelizumab, cyclophosphamide, mitoxantrone, total body irradiation, bone marrow transplantation, alemtuzumab, daclizumab) 2. Are currently receiving or require initiation of any of the following therapies: • Treatment with corticosteroids at a dose that exceeds the prednisone equivalent of > 40 mg per day • Treatment with immunosuppressive agents (e.g., azathioprine, 6-MP, or methotrexate) • Chronic non-steroidal anti-inflammatory drug (NSAID) use (Note: occasional use of NSAIDs and acetaminophen [eg, headache, arthritis, myalgias, or menstrual cramps] and aspirin up to 325 mg/day is permitted) • Treatment with Class Ia or Class III anti-arrhythmic drugs or treatment with two or more agents in combination known to prolong PR interval 3. Are receiving treatment with any of the following drugs or interventions within the corresponding timeframe: - At Day 1 - CYP2C8 inhibitors (eg, gemfibrozil or clopidogrel) or inducers (eg, rifampicin) - Two weeks prior to Day 1 - Monoamine oxidase inhibitors (eg, selegiline, phenelzine) 4. Are receiving treatment with breast cancer resistance protein (BCRP) inhibitors (eg, cyclosporine, eltrombopag) Exclusions Related to General Health: 5. Pregnancy, lactation, or a positive serum beta human chorionic gonadotropin (hCG) 6. Clinically relevant hepatic, neurological, pulmonary, ophthalmological, endocrine, psychiatric or other major systemic disease making implementation of the protocol or interpretation of the trial difficult or that would put the patient at risk by participating in the trial or that would have required a patient to discontinue treatment in the previous RPC1063 trial 7. Clinically relevant cardiovascular conditions, including history or presence of recent myocardial infarction, unstable angina, stroke, transient ischemic attack, decompensated heart failure requiring hospitalization, Class III/IV heart failure, sick sinus syndrome, or severe untreated sleep apnea Exclusions Related to Laboratory Results: 8. Liver function impairment or persisting elevations of aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 5 times the upper limit of normal (ULN), or direct bilirubin > 3 times the ULN 9. Forced expiratory volume at 1 second (FEV1) or (forced vital capacity) FVC < 50% of predicted values. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Due to the open-label nature of the trial and the lack of a control group, all data will be summarized and no hypothesis testing will be performed. Each efficacy endpoint will be summarized and 95% confidence intervals around the estimates may also be presented.
Efficacy Endpoints: • Proportion of patients in clinical remission. • Proportion of patients with a clinical response • Proportion of patients with endoscopic improvement • Proportion of patients with mucosal healing • Proportion of patients with corticosteroid-free remission • Change from Baseline in complete Mayo score, partial Mayo score, and 9-point Mayo score • Proportion of patients with histologic remission • Proportion of patients with clinical response, clinical remission, or endoscopic improvement in patients who had previously received anti-TNF therapy
Safety Endpoints: The incidence, severity, and relationship of treatment-emergent adverse events (TEAEs), serious AEs (SAEs), TEAEs leading to discontinuation of investigational drug, AEs of special interest (AESIs), and TEAEs of special interest (Exploratory) Changes from Baseline for clinical laboratory measures, vital signs, ECGs, and pulmonary function tests |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Efficacy assessments will be performed at the following visits; Day 1 (Baseline/Visit 1) - All Week 5 (Visit 2) Week 10 (Visit 3) Week 16 (Visit 4) Week 22 (Visit 5) Thereafter, additional visits at 12-week intervals (Visit 5 onwards).
Partial Mayo partial score assessment to be performed at each visit. Full Mayo score assessment performed at Visit 1, Visit 7, at each additional visit (12-week intervals), and at the End of Treatment/Early Termination Visit.
Endoscopy and colonic biopsies will be performed at Week 1, Visit 7, at each additional visit (12-week intervals), and at the End of Treatment/Early Termination Visit. |
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E.5.2 | Secondary end point(s) |
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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 | 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 | 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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 104 |
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 |
New Zealand |
Moldova, Republic of |
Ukraine |
Australia |
Belarus |
Canada |
Georgia |
Israel |
Korea, Republic of |
Russian Federation |
Serbia |
South Africa |
United Kingdom |
United States |
Belgium |
Bulgaria |
Croatia |
Czechia |
Germany |
Hungary |
Italy |
Netherlands |
Poland |
Romania |
Slovakia |
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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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Patients will receive treatment until the end of March 2023, unless the Sponsor discontinues the development program. |
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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 | 9 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 25 |
E.8.9.2 | In all countries concerned by the trial years | 9 |
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 | 25 |