E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Relapsing-remitting multiple sclerosis (RRMS) |
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E.1.1.1 | Medical condition in easily understood language |
|
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 | 21.1 |
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 |
|
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 evaluate the efficacy of natalizumab extended interval dosing (EID) in
subjects who have previously been treated with natalizumab standard interval dosing (SID) for at least
12 months, in relation to continued SID treatment. |
|
E.2.2 | Secondary objectives of the trial |
The secondary objectives are to evaluate additional clinical and MRI based efficacy endpoints, and safety of
EID in subjects who have previously been treated with natalizumab SID for at least 12 months, in relation to
continued SID treatment. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Ability of the participant to understand the purpose and risks of the study and provide signed and dated
informed consent and authorization to use confidential health information in accordance with national and local participant privacy regulations.
• Diagnosis of relapsing remitting multiple sclerosis (RRMS) according to the McDonald criteria [Thompson
2018].
• Treatment with natalizumab as disease-modifying monotherapy for RRMS that is consistent with the
approved dosing for a minimum of 12 months prior to randomization. The participant must have received at
least 11 doses of natalizumab in the 12 months prior to randomization with no missed doses in the 3 months
prior to randomization.
• Expanded Disability Status Scale (EDSS) <=5.5 at screening.
• No relapses in the last 12 months prior to randomization, as determined by the enrolling Investigator
NOTE: Other protocol-defined inclusion criteria may apply. |
|
E.4 | Principal exclusion criteria |
• Primary and secondary progressive multiple sclerosis (MS).
• MRI positive for Gd-enhancing lesions at screening.
• Participants for whom MRI is contraindicated (e.g., have a contraindicated pacemaker or other contraindicated implanted metal device, have suffered, or are at risk for, side effects from Gd, or have claustrophobia that cannot be medically managed).
• History of any clinically significant (as determined by the Investigator) cardiac, endocrinologic, hematologic, hepatic, immunologic, metabolic (including diabetes), urologic, pulmonary, neurologic (except for RRMS), dermatologic, psychiatric, renal, or other major disease that would preclude participation in a clinical
study, in the opinion of the Investigator.
• Presence of anti-natalizumab antibodies at screening.
NOTE: Other protocol-defined exclusion criteria may apply. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Number of New or Newly Enlarging T2 Hyperintense Lesions at Week 72 |
|
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 First Relapse as Adjudicated by an Independent Neurology Evaluation Committee (INEC)
•Number of new Gadolinium (Gd) Enhancing and new T1 Hypointense Lesions at Weeks 24, 48 and 72
•Annualized Relapse Rate at Week 72
•Number of New or Newly Enlarging T2 Hyperintense Lesions at Weeks 24 and 48
•Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
•Time to Expanded Disability Status Scale (EDSS) worsening |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Variable time frames throughout the study |
|
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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
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 | Yes |
E.8.1.1 | Randomised | Yes |
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 | Yes |
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 | Yes |
E.8.2.3.1 | Comparator description |
Comparison between 2 different treatment frequencies of the same drug. |
|
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 | 10 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 40 |
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 |
Australia |
Canada |
Israel |
New Zealand |
United States |
Belgium |
France |
Germany |
Italy |
Netherlands |
Spain |
United Kingdom |
|
E.8.7 | Trial has a data monitoring committee | No |
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
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 2 |
E.8.9.2 | In all countries concerned by the trial days | 0 |