Relapsing-remitting multiple sclerosis (RRMS) MedDRA version: 21.1 Level: PT Classification code 10063399 Term: Relapsing-remitting multiple sclerosis System Organ Class: 10029205 - Nervous system disorders
Conditions
Sponsors
Biogen Idec Research Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: For Part 1: • 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) =65 years) no F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
Exclusion criteria: For Part 1: • 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. For Part 2: • Participants treated with natalizumab EID was reverted to natalizumab SID by choice or as rescue treatment in Part 1. • Participant received treatment with any MS disease-modifying therapy other than natalizumab in Part 1 or in the period between Part 1 and Part 2. • History of human immunodeficiency virus or history of other immunodeficient conditions. • Current enrollment or a plan to enroll in any interventional clinical study in which an investigational treatment or approved therapy for investigational use is administered within 30 days (or 5 half-lives of the agent, whichever is longer) prior to the Baseline Visit or at any time during this study. • Inability to comply with study requirements. • Other unspecified reasons that, in the opinion of the Investigator or Biogen, make the participant unsuitable for enrollment. The inclusion and exclusion criteria for new participants who did not participate in Part 1 of the study are the same as those for participants who did participate in Part 1. NOTE: Other protocol-defined exclusion criteria may apply.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): Part 1: Number of New or Newly Enlarging T2 Hyperintense Lesions at Week 72 Part 2: Percentage of Participants Indicating a Preference for Natalizumab SC Administration at the End of Part 2;Timepoint(s) of evaluation of this end point: Part1: Week 72 Part2: Week 156;Main Objective: Part1: 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. Part 2: The primary objective is to evaluate participant preference for subcutaneous (SC) versus intravenous (IV) route of natalizumab administration.;Secondary Objective: Part 1: 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. Part2: The secondary objectives is to evaluate treatment satisfaction, drug preparation and administration time, safety and immunogenicity, efficacy and characterize pharmacokinetic (PK) and pharmacodynamic (PD) drug preparation and administration time of SC versus IV routes of natalizumab administration. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Part 1: •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 Weeks 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 Part 2: • Total Score on Treatment Satisfaction Questionnaire for Medication (TSQM) • Mean Time for Drug Preparation and Administration • Number of Participants with Treatment Emergent AEs (TEAEs) • Percentage of Participants With Anti-Natalizumab Antibodies • Number of New or Newly Enlarging T2 Hyperintense Lesions • Time to First Relapse • Annualized Relapse Rate • Change in Expanded Disability Status Scale (EDSS) Score • Number of New Gadolinium (Gd) Enhancing Lesions • Number of New T1 Hypointense Lesions • Percentage of Brain Volume Change • Change in Cortical and Thalamic Brain Region Volume • Trough Serum Concentration of Natalizumab (Ctrough) • Part 2: Trough a4 Integrin Saturation;Timepoint(s) of evaluation of this end point: Variable time frames throughout the study | — |
Countries
Australia, Belgium, Canada, France, Germany, Israel, Italy, Netherlands, New Zealand, Spain, United Kingdom, United States
Outcome results
None listed