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 is characterized by relapses followed by periods of full or partial recovery. |
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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 | 17.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10063399 |
E.1.2 | Term | Relapsing-remitting multiple sclerosis |
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 |
The primary objective of this study is to assess whether the efficacy of ocrelizumab 600 mg intravenously every 24 weeks is superior to Rebif® as measured by the annualized protocol-defined relapse rate by two years in patients with relapsing multiple sclerosis. |
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E.2.2 | Secondary objectives of the trial |
To evaluate whether the efficacy of ocrelizumab is superior to Rebif®, as reflected by the following measures:
• The time to onset of confirmed disability progression for at least 12 weeks with the initial event of neurological worsening occurring during the 96-week, double-blind, double-dummy, treatment period.
• The total number of T1 Gd-enhancing lesions as detected by brain MRI at weeks 24, 48 and 96
• The total number of new, and/or enlarging T2 hyperintense lesions as detected by brain MRI at Weeks 24, 48, and 96.
• The proportion of patients who have confirmed disability improvement for at least 12 weeks initial event of neurological improvement occurring during the 96-week, double-blind, double-dummy, treatment period.
• The time to onset of confirmed disability progression for at least 24 weeks with the initial event of neurological worsening ocurring during the 96-week, double-blind, double-dummy, treatment period.
See Section 2.2 of the protocol for full list |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Consenting patients who enrolled in the main study WA21092 and who are eligible will be offered the opportunity to participate in these optional substudies.
1. Optical Coherence Tomography Exploratory Substudy
This substudy will be conducted at certain selected centers and will be used to evaluate the neuroprotectie effect of ocrelizumab as measured by retinal nerve fiber layer (RNFL) thickness and macular volume in both eyes.
2. BE29354 - Substudy for the assessment of ocrelizumab treatment effects on disability of MS patients enrolled in the phase III Orchestra programme using multimodal Evoked Potentials (mEP) and high-resolution electroencephalogram (EEG)
3. BE29353 - Substudy to investigate B Cell and T Cell Repertoires in Ocrelizumab-treated MS Patients
4. BE29352 - Substudy of brain and spinal cord MRI in multiple sclerosis patients participating in the OPERA clinical trial
5. BE29340 - Substudy of brain myelin mapping to quantify demyelination and repair in Ocrelizumab-treated MS Patients |
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E.3 | Principal inclusion criteria |
Male and female patients between ages 18-55 with a diagnosis of relapsing multiple sclerosis
At least 2 documented clinical attacks within the last 2 years prior to screening or one clinical attack in the year prior to screening (but not within 30 days prior to screening)
Patients with EDSS score of 0-5.5
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E.4 | Principal exclusion criteria |
Patients with other chronic disease of the immune system, malignancies or other diseases or conditions that could preclude patient from participating in the study
Contraindications to or intolerance of oral or i.v. corticosteroids
Contraindication to or intolerance of interferon beta-1a (Rebif)
Pregnant or nursing women
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E.5 End points |
E.5.1 | Primary end point(s) |
Annualized protocol-defined relapse rate at |
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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) |
1. The time to onset of confirmed disability progression for at least 12 weeks with the initial event of neurological worsening occurring during the 96-week, double-blind, double-dummy, treatment period
2. The total number of T1 Gd-enhancing lesions as detected by brain MRI
3. The total number of new, and/or enlarging T2 hyperintense lesions as detected by brain MRI
4.The proportion of patients who have confirmed disability improvement for at least 12 weeks, with the initial event of neurological improvement occurring during the 96-week double-blind, double-dummy treatment period.
5. The time to onset of confirmed disability progression for at least 24 weeks with the initial event of neurological worsening occurring during the 96-week, double-blind, double-dummy, treatment period
6. The total number of T1-hypo-intense lesions (chronic black holes)
7. The change in MSFCS score
8. The percentage change in brain volume as detected by brain MRI
9. The change in SF-36 PCS Score
10. The proportion of patients who have NEDA
Additional exploratory endpoints as defined in the protocol |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Assessed throughout the study
2. At Weeks 24, 48, and 96
3. At Weeks 24, 48, and 96.
4. Assessed throughout the study
5. Assessed throughout the study
6. At Weeks 24, 48, and 96
7. Baseline to Week 96
8. From Week 24 to Week 96.
9. Baseline to Week 96
10. By Week 96 |
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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 | Yes |
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 | Yes |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 92 |
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 |
Brazil |
Chile |
Israel |
Mexico |
Morocco |
New Zealand |
Peru |
Russian Federation |
Serbia |
South Africa |
Switzerland |
Tunisia |
Ukraine |
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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LPLV in the: OLE Phase OR B-cell monitoring of Safety Follow-Up Period, whichever is later. OLE Phase continues until: ocrelizumab is commercially available locally; as per local regulation; should the Sponsor decide to terminate the program for MS; but will not exceed 4 years after the last patient to reach the Wk96 visit in the blinded phase. The Safety Follow-Up Period of each patient will last until the B-cell count has returned to the baseline value or to the LLN range (whichever is lower). |
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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 | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 6 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |