The purpose of this study is to determine whether long-term RPC1063 is safe and effective in the treatment of ulcerative colitis (UC).

• Register: EUCTR
• Last refreshed on: 12 March 2024
• Main ID: EUCTR2015-001600-64-DE
• Date of registration: 04/08/2015
• Prospective Registration: Yes
• Primary sponsor: Celgene International II Sàrl (CIS II)
• Public title: The purpose of this study is to determine whether long-term RPC1063 is safe and effective in the treatment of ulcerative colitis (UC).
• Scientific title: A Phase 3, Multicenter, Open-Label Extension Trial of Oral RPC1063 as Therapy for Moderate to Severe Ulcerative Colitis - Efficacy and Safety Study of long-term RPC1063 in Ulcerative Colitis
• Date of first enrolment: 13/11/2015
• Target sample size: 1350
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-001600-64
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Australia, Austria, Belarus, Belgium, Bulgaria, Canada, Croatia, Czech Republic, Czechia, Germany, Greece, Hungary, Israel, Italy, Korea, Republic of, Latvia, Netherlands, New Zealand, Poland, Russian Federation, Slovakia, South Africa, Spain, Ukraine, United Kingdom, United States

Contacts

• Name: Truenorth Study Information Center
• Affiliation: Celgene International II Sarl

• Name: Truenorth Study Information Center
• Affiliation: Celgene International II Sarl

Key inclusion & exclusion 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 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
*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 postmeopausal for at least 24 consecutive months (that is, has had menses at any time during the preceding 24 consecutive months)
**Contaception Education: Counselling about pregnancy prcautions 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 Basline Visits. The patient will be re-educated every time her contrceptive measures/methods or ability to become pregnant changes. The female patient's chosen form of contraception must be effective by the time the femal patient is randomized into the study (for example, hormonal contraception should be initiated at least 28 days before baseline).
Periodic abstinence (calendar, symptothermal, post-ovulaiton methods), withdrawal (coitus interruptus), spermicides only, and lactational amenorrhea method are not acceptable methods of contraception.
3. Must provide written informed consent and have the ability to be compliant with the schedule of protocol assessments, which must be
obtained prior to any trial-related procedures.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 1164
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 36

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, 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)
• 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 (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 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 < 50% of predicted values


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Ulcerative colitis
MedDRA version: 20.1 Level: LLT Classification code 10045365 Term: Ulcerative colitis System Organ Class: 100000004856

Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

Intervention(s)

Trade Name: ZEPOSIA® (ozanimod)
Product Name: 0.25 mg RPC1063
Product Code: RPC1063
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Ozanimod
Current Sponsor code: RPC1063
Other descriptive name: (S)-5-(3-(1-((2-hydroxyethyl)amino)-2,3-dihydro-1H-inden-4-yl)-1,2,4-oxadiazol-5-yl)-2-isopropoxybenzonitrile hydrochloride
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 0.25-

Trade Name: ZEPOSIA® (ozanimod)
Product Name: 1.0 mg RPC1063
Product Code: RPC1063
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Ozanimod
Current Sponsor code: RPC1063
Other descriptive name: (S)-5-(3-(1-((2-hydroxyethyl)amino)-2,3-dihydro-1H-inden-4-yl)-1,2,4-oxadiazol-5-yl)-2-isopropoxybenzonitrile hydrochloride
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1.0-

Primary Outcome(s)

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, 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
Plasma protein biomarkers (cytokines, chemokines, other markers of inflammation)
- Stool biomarkers (eg FCP)
- Mucosal tissue inflammatory biomarkers (eg, lymphocyte subsets)
- Exploratory measurements of immune response (e.g. SARS-CoV-2
serology), from blood samples collected after the amendment, every 6
months thereafter and end of treatment, and the potential association
between these measurements and selected endpoints related to safety,
efficacy, and/or biomarkers.

Main Objective: Evaluate the long-term safety of RPC1063 for the treatment of all patients with moderate to severe UC.
Evaluate the long-term safety of RPC1063 for the treatment of adult patients with moderate to severe UC.

Secondary Objective: Not applicable

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)
Week34 (Visit 6)
Week 46 (visit 7)
Thereafter, additional visits at 24-week intervals (Visit 8 onwards).

Partial Mayo partial score assessment to be performed at each visit.
Full Mayo score assessment performed at Visit 1, Visit 7, and after that, at 48-week intervals (i.e.. Week 94, Week 142, etc.) and at the End of Treatment/Early Termination Visit.

Endoscopy and colonic biopsies will be performed at Week 1, Visit 7, and after that, at 48-week intervals (i.e.. Week 94, Week 142, etc.) and at the End of Treatment/Early Termination Visit.

Secondary Outcome(s)

Secondary end point(s): Not applicable

Timepoint(s) of evaluation of this end point: Not applicable

Secondary ID(s)

NCT02531126

2015-001600-64-CZ

RPC01-3102

Source(s) of Monetary Support

Celgene International II Sàrl (CIS II)

Ethics review

Status: Approved
Approval date: 13/11/2015
Contact: