inflammatory bowel disease ulcerative colitis
Conditions
Interventions
Patients will receive treatment until the patient completes 5 years (Week 238)
and the Safety Follow-up Visit, unless the Sponsor discontinues the development
program. Patients who are not in clinic
Sponsors
Celgene International II Sàrl
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Previously participated in a trial of RPC1063 (eg, RPC01-3101 or completed at least 1 year of the open-label period for RPC01-202) and meet the criteria for participation in the open label extension as outlined in the prior trial. 2. Female 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 -vasectomised partner -complete sexual abstinence For the purposes of this study, a female patient is considered to be of childbearing potential if she has reached menarche, and 1) has not undergone a hysterectomy (the surgical removal of the uterus) or bilateral oophorectomy (the surgical removal of both ovaries) or 2) has not been postmenopausal for at least 24 consecutive months (that is, has had menses at any time during the preceding 24 consecutive months) **Contraception Education: Counselling about pregnancy precautions and the potential risks of fetal exposure must be conducted for FCBP. The Investigator will educate all FCBP about the different options of contraceptive methods or abstinence, as appropriate, at the Screening and Baseline Visits. The patient will be re-educated every time her contraceptive measures/methods or ability to become pregnant changes. The female patient's chosen form of contraception must be effective by the time the female patient is randomized into the study (for example, hormonal contraception should be initiated at least 28 days before baseline). Periodic abstinence (calendar, symptothermal, post-ovulation methods), withdrawal (coitus interruptus), spermicides only, and lactational amenorrhoea method are not acceptable methods of contraception. 3. Must provide written informed consent/assent and have the ability to be compliant with the schedule of protocol assessments, which must be obtained prior to any trial-related procedures.
Exclusion criteria
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 D-penicillamine, leflunomide, thalidomide, natalizumab or fingolimod, etrasimod, or tofacitinib • Treatment with lymphocyte-depleting therapies (e.g., Campath, anti-CD4, cladribine, rituximab, ocrelizumab, cyclophosphamide, alemtuzumab, daclizumab) • Treatment with a live vaccine or live attenuated vaccine within 4 weeks prior to Visit 1 of this trial., 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 • Treatment with immunosuppressive agents immunosupressive 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 indcers (eg, rifampicin) Two weeks prior to Day 1 - Monamine 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 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. FEV1 or FVC
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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 will be summarized. - Exploratory safety endpoints include changes from baseline for clinical laboratory measures, vital signs, ECGs, and pulmonary function tests. Other Exploratory Endpoints: - Absolute lymphocyte count (ALC) derived from hematology laboratory results - Blood biomarkers (cytokines, chemokines, other markers of inflammation) - Stool biomarkers (eg FCP) - Mucosal tissue blood biomarkers (eg, lymphocyte subsets) - Exploratory measurements of immune response (e.g. SARS-CoV-2 serology), from blood samples (processed for serum only) collected after the amendment, every 48 weeks thereafter and end of treatment, and the potential association between these measurements and selected endpoints related to safety, efficacy, and/or biomarkers. | — |
Secondary
| Measure | Time frame |
|---|---|
| As this is an open-label extension trial for patients who previously participated in a trial of RPC1063 for UC, there is no statistical basis for the sample size. All endpoints are therefore described under primary endpoints. | — |
Countries
Netherlands
Outcome results
None listed