E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Relapsing Multiple Sclerosis |
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E.1.1.1 | Medical condition in easily understood language |
Relapsing Multiple Sclerosis |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
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 | 10048393 |
E.1.2 | Term | Multiple sclerosis relapse |
E.1.2 | System Organ Class | 10029205 - Nervous system 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 |
To characterize the long-term safety and tolerability of RPC1063 in patients with relapsing multiple sclerosis. |
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E.2.2 | Secondary objectives of the trial |
To characterize the long-term efficacy of RPC1063 in patients with relapsing multiple sclerosis. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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: RPC01-201 or RPC01-301
2. Does not have a condition that would require withdrawal from one of the parent trials (RPC01-201 or RPC01-301)
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 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 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
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. |
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E.4 | Principal exclusion criteria |
Patients that have a condition that would require withdrawal from one of the parent trials (RPC01-201 or RPC01-301) |
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E.5 End points |
E.5.1 | 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.
In addition, dependence and withdrawal symptoms will be assessed in at least 80 evaluable patients who discontinue study drug using the following assessments: PWC-20, HADS, ESS , vital signs, and the C-SSRS. Changes from last on-study-drug assessment for each withdrawal scale (PWC-20, HADS, ESS, C-SSRS and vital signs) to post study drug Day 1, 4, 7, 14, 21, and 90 will be summarized.
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 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Every 3 month visit, every 6 Month Visit for subjects who have completed their 3rd annual visit, follow-up visit and during the unscheduled relapse visit if applicable |
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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 | Yes |
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.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 199 |
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 |
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 |
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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 | 6 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 19 |
E.8.9.2 | In all countries concerned by the trial years | 7 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 1 |