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] - 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 |
Demonstrate that ofatumumab 20 mg sc once every 4 (q4) weeks is superior to teriflunomide 14 mg po once daily in reducing the frequency of confirmed relapses as evaluated by the annualized relapse rate (ARR) in patients with relapsing MS. |
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E.2.2 | Secondary objectives of the trial |
Key secondary objectives
To evaluate if ofatumumab is superior to teriflunomide on:
1. Time to disability worsening as measured by 3-month confirmed worsening (3mCDW) on EDSS
2. Number of T1 GdE lesions per MRI scan
3. Number of new or enlarging T2 lesions on MRI per year (annualized T2 lesion rate)
4. Time to disability worsening as measured by 6-month confirmed worsening (6mCDW) on EDSS
5. Rate of brain volume loss (BVL) based on assessments of percentage brain volume change from baseline
6. Time to disability improvement, as measured by 6-month confirmed improvement (6mCDI) on EDSS
improvement (6mCDI) on EDSS
7. Neurofilament light chain (NfL) concentration in serum
See protocol for complete list of secondary objectives. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
•Male or female patients aged 18 to 55 years (inclusive) at screening
•Diagnosis of MS according to the 2010 Revised McDonald criteria
•Relapsing form of MS: relapsing-remitting course (RRMS), or secondary progressive course with disease activity (relapsing SPMS)
•Disability status at Screening with an EDSS score of 0 to 5.5 (inclusive)
•At least 1 documented relapse during the previous 1 year OR at least 2 documented relapses during the previous 2 years OR a positive GdE MRI scan during the year prior to randomization and including screening.
•Neurologically stable within 1 month prior to randomization
Please see protocol for complete detailed list of inclusion criteria |
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E.4 | Principal exclusion criteria |
•Patients with primary progressive MS or SPMS without disease activity
•Disease duration of more than 10 years in patients with EDSS score of 2 or less
•Pregnant or nursing (lactating) women
•Women of child-bearing potential not using highly effective contraception
•Patients with an active chronic disease
•Patients with active systemic infections, or history of or known presence of recurrent or chronic infection
•Have received any live or live-attenuated vaccines within 2 months prior to randomization
•Have been treated with medications as specified within the timeframes specified (e.g. ofatumumab, rituximab, ocrelizumab, alemtuzumab, natalizumab, cyclophosphamide, teriflunomide, etc)
•Any other disease or condition which could interfere with participation in the study according to the study protocol, or with the ability of the patients to cooperate and comply with the study procedures.
Please see protocol for complete detailed list of exclusion criteria |
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E.5 End points |
E.5.1 | Primary end point(s) |
Demonstrate that ofatumumab 20 mg sc once every 4 (q4) weeks is superior to teriflunomide 14 mg po once daily in reducing the frequency of confirmed relapses as evaluated by the annualized relapse rate (ARR) in patients with relapsing MS. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
-Time to disability worsening as measured by 3-month confirmed worsening (3mCDW) on The Expanded Disability Status Scale (EDSS).
-Time to disability worsening as measured by 6-month confirmed worsening (6mCDW) on EDSS.
-Time to disability improvement as measured by 6-month confirmed improvement (6mCDI) on EDSS.
-Number of T1 Gd-enhancing lesions per MRI scan.
-Number of new or enlarging T2 lesions on MRI per year (annualized T2 lesion rate).
-Rate of brain volume loss (BVL) based on assessments of percentage brain volume change from baseline.
-Neurofilament light chain (NfL) concentration in serum.
See protocol for complete list of secondary end points. |
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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 | Yes |
E.6.11 | Pharmacogenomic | Yes |
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 | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 77 |
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 |
Australia |
Canada |
India |
Israel |
Mexico |
Russian Federation |
Switzerland |
Thailand |
Turkey |
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 | 2 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | 1 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 9 |