Phase 3
N=499
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
Bottom Line
View on ClinicalTrials.gov: NCT03689972 ↗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
| Outcome | Result | p-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
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.