A Multi-Site, Open-Label Extension Trial of Oral RPC1063 in Relapsing Multiple Sclerosis

• Register: EUCTR
• Last refreshed on: 28 February 2019
• Main ID: EUCTR2015-002500-91-HU
• Date of registration: 26/08/2015
• Prospective Registration: Yes
• Primary sponsor: Celgene International II Sàrl (CIS II)
• Public title: A Multi-Site, Open-Label Extension Trial of Oral RPC1063 in Relapsing Multiple Sclerosis
• Scientific title: A Multi-Site, Open-Label Extension Trial of Oral RPC1063 in Relapsing Multiple Sclerosis - Open Label Extension (OLE) study
• Date of first enrolment: 12/10/2015
• Target sample size: 2496
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-002500-91
• 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 Number of treatment arms in the trial: 1
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Belarus, Belgium, Bosnia and Herzegovina, Bulgaria, Croatia, Estonia, Georgia, Germany, Greece, Hungary, Italy, Latvia, Lithuania, Moldova, Republic of, New Zealand, Poland, Portugal, Romania, Russian Federation, Serbia, Slovakia, South Africa, Spain, Sweden, Ukraine, United Kingdom, United States

Contacts

• Name: Project Manager
• Affiliation: PPD

• Name: Project Manager
• Affiliation: PPD

Key inclusion & exclusion criteria

Inclusion criteria:
To be eligible to participate in this trial, patients must meet all of the following criteria:
1. Completed one of the parent trials
2. Does not have a condition that would require withdrawal from one of the parent trials
3. Has no conditions requiring treatment with a prohibited concomitant medication
4. Is not receiving treatment with any of the following drugs or interventions within the
corresponding timeframe:
At Baseline (Day 1)
CYP2C8 inhibitors (eg, gemfibrozil or clopidogrel) or inducers (eg, rifampicin)
Two weeks prior to Baseline (Day 1)
Monoamine oxidase inhibitors (eg, selegiline, phenelzine)
5. Ability to provide written informed consent and to be compliant with the schedule of protocol assessments
6. Female patients of childbearing potential:
Must agree to practice a highly effective method of contraception throughout the study until completion of the 75-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 this study 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
-Sexual abstinence

Male patients:
Must agree to use a latex condom during sexual contact with women of childbearing potential while participating in the study until completion of the 75-day Safety Follow-up Visit.

All patients:
Periodic abstinence (calendar, symptothermal, post-ovulation methods), withdrawal (coitus interruptus), spermicides only, and lactational amenorrhoea method (LAM) are not acceptable methods of contraception. Female condom and male condom should not be used together.
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 2496
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
Patients that have a condition that would require withdrawal from one of the parent trials (RPC01-201 or RPC01-301)


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

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Relapsing Multiple Sclerosis
MedDRA version: 20.0 Level: PT Classification code 10048393 Term: Multiple sclerosis relapse System Organ Class: 10029205 - Nervous system disorders

Intervention(s)

Product Name: 0.25mg RPC1063
Product Code: RPC1063
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Ozanimod
Current Sponsor code: RPC1063
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 0.25-

Product Name: 1.0mg RPC1063
Product Code: RPC1063
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Ozanimod
Current Sponsor code: RPC1063
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1.0-

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: Every 3 month visit, follow-up visit and during the unscheduled relapse visit if applicable

Main Objective: To characterize the long-term safety and tolerability of RPC1063 in patients with relapsing multiple sclerosis.

Primary end point(s): Safety Endpoints
Safety and tolerability will be characterized in this trial by the incidence, relationship, and type of adverse events, serious adverse events, and adverse events leading to withdrawal from the trial; the incidence, relationship, and type of laboratory abnormalities; vital signs; electrocardiogram results; and physical examination abnormalities. Suicidality (Columbia-Suicide Severity Rating Scale) will be assessed in the trial. In addition, descriptive characterization will be provided for adverse events of special interest including bradycardia and heart conduction abnormalities (electrocardiogram and vital signs), pulmonary effects (forced expiratory volume at 1 second, forced vital capacity, and diffusing capacity of the lung for carbon monoxide measurements), macular edema (optical coherence tomography), hepatic effects (liver function tests), serious or opportunistic infections, and malignancy (see Protocol Section 12.4.2 for the complete list of AESIs).

Efficacy Endpoints
- Annualized relapse rate
- Time to first relapse
- The number of new or enlarging hyperintense T2-weighted brain magnetic resonance imaging lesions at each visit
- The number of gadolinium-enhanced brain magnetic resonance imaging lesions at each visit
-Time to onset of disability progression as defined by a sustained worsening in Expanded Disability Status Scale of 1.0 points or more from baseline, confirmed after 3 months and after 6 months
- Proportion of patients who are free of gadolinium-enhanced lesions at each visit
- Proportion of patients who are free of new or enlarging T2 lesions at each visit
- Percent change in normalized brain volume (atrophy) on brain magnetic resonance imaging scans from Baseline at each visit
-Change in Multiple Sclerosis Functional Composite score from Baseline at each visit (including the Low-Contrast Letter Acuity Test measurement of visual function as a component)
-Change in Multiple Sclerosis Quality of Life 54 score from Baseline at each visit
-Changes in other magnetic resonance imaging variables including but not limited to, number and volume of gadolinium-enhanced T1 lesions, volume of T2 lesions, number of new or enlarging T2 lesions, volume of unenhancing T1 lesions, number of new unenhancing T1 lesions

Secondary Objective: To characterize the long-term efficacy of RPC1063 in patients with relapsing multiple sclerosis.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: N/A

Secondary end point(s): None

Secondary ID(s)

NCT02576717

RPC01-3001

Source(s) of Monetary Support

Celgene International II Sàrl (CIS II)

Ethics review

Status: Approved
Approval date:
Contact: