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Phase 3 N=499 Randomized Treatment

A Study to Evaluate Efficacy, Safety, and Tolerability of EID of Natalizumab (BG00002) in Participants With RRMS Switching From Treatment With Natalizumab SID in Relation to Continued SID Treatment- Followed by Extension Study Comprising SC and IV Natalizumab Administration

Multiple Sclerosis, Relapsing-Remitting

Enrolled (actual)
499
Serious AEs
4.7%
Results posted
Jun 2024
Primary outcome: Primary: Part 1: Mean Number of New or Newly Enlarging T2 Hyperintense Lesions at Week 72 — 0.05; 0.20 number of T2 lesions — p==0.0755

Study Design & Population

Study type
Interventional
Phase
Phase 3
Interventions
Natalizumab (Drug)
Age
Adult · 18+ yrs
Sex
All
Sponsor
Biogen
Primary completion
Jan 2023

Outcome Measures

OutcomeResultp-value
PRIMARY
Part 1: Mean Number of New or Newly Enlarging T2 Hyperintense Lesions at Week 72
0.05; 0.20 =0.0755
PRIMARY
Part 2: Percentage of Participants Indicating a Preference for Natalizumab SC Administration at the End of Crossover Period of Part 2
83.9; 91.8
SECONDARY
Part 1: Time to First Relapse as Adjudicated by an Independent Neurology Evaluation Committee (INEC)
NA; NA
SECONDARY
Part 1: Annualized Relapse Rate at Week 72
0.00010; 0.0001 =0.6312
SECONDARY
Part 1: Time to Expanded Disability Status Scale (EDSS) Worsening
NA; NA
SECONDARY
Part 1: Mean Number of New T1 Hypointense Lesions at Weeks 24, 48, and 72
0.0; 0.0; 0.0; 0.0; 0.0; 0.0
SECONDARY
Part 1: Mean Number of New or Newly Enlarging T2 Hyperintense Lesions at Weeks 24 and 48
0.0; 0.0; 0.0; 0.1
SECONDARY
Part 1: Mean Number of New Gadolinium (Gd) Enhancing Lesions at Weeks 24, 48, and 72
0.0; 0.0; 0.0; 0.0; 0.0; 0.1
SECONDARY
Part 1: Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
76.9; 77.6; 6.9; 6.8
SECONDARY
Part 2: Change From Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) Scores During the Crossover Period
0.17; 0.64 =0.764
SECONDARY
Part 2: Mean Time for Drug Preparation and Drug Administration During the Crossover Period
4.9; 0; 62.6; 4.3
SECONDARY
Part 2: Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs)
57.4; 62.9
SECONDARY
Part 2: Percentage of Participants With Anti-Natalizumab Antibodies During the Crossover Period
0; 0
SECONDARY
Part 2: Mean Number of New or Newly Enlarging T2 Hyperintense Lesions During the Crossover Period
0.0; 0.0
SECONDARY
Part 2: Time to First Relapse During the Crossover Period
NA; NA
SECONDARY
Part 2: Annualized Relapse Rate During the Crossover Period
SECONDARY
Part 2: Change From Baseline in EDSS Score During the Crossover Period
0.02; 0.10 =0.357
SECONDARY
Part 2: Mean Number of New Gd Enhancing Lesions During the Crossover Period
0.0; 0.0
SECONDARY
Part 2: Mean Number of New T1 Hypointense Lesions During the Crossover Period
0.0; 0.0
SECONDARY
Part 2: Mean Percentage Change From Baseline in Brain Volume During the Crossover Period
-0.11; -0.10
SECONDARY
Part 2: Change From Baseline in Cortical and Thalamic Brain Region Volume During the Crossover Period
-1478.82; -881.34; -25.98; -17.96
SECONDARY
Part 2: Trough Serum Concentration of Natalizumab (Ctrough) During the Crossover Period
11.9; 10.3
SECONDARY
Part 2: Mean Trough α4 Integrin Saturation During the Crossover Period
71.2; 67.2

Summary

Part 1: The primary objective is to evaluate the efficacy of natalizumab extended interval dosing (EID) (every 6 weeks [Q6W]) in participants who have previously been treated with natalizumab standard interval dosing (SID) (every 4 weeks [Q4W]) for at least 12 months, in relation to continued Q4W treatment. The secondary objectives is to evaluate relapse-based clinical efficacy measures, disability worsening, additional Magnetic resonance imaging (MRI)-lesion efficacy measures and safety of Q6W in participants who have previously been treated with natalizumab Q4W for at least 12 months, in relation to continued Q4W treatment. Part 2: The primary objective is to evaluate participant preference for subcutaneous (SC) versus intravenous (IV) route of natalizumab administration. 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.

Eligibility Criteria

Key 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) score <=5.5 at screening.
  • No relapses in the last 12 months prior to randomization, as determined by the enrolling Investigator.

For Part 2:

  • Ability of the participants to understand the purpose and risks of the study and provide signed and dated informed consent for Part 2 and authorization to use confidential health information in accordance with national and local participant privacy regulations.
  • Completed Part 1 Week 72 visit while remaining on their randomized treatment assignment of Q4W or Q6W.

Key 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 Q6W was reverted to natalizumab Q4W 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 Inclusion/Exclusion criteria may apply

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT03689972). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.

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