NCT05532163TerminatedPhase 4
A Prospective, Multicenter, Interventional, Open-Label, Single-arm Phase IV Study Over 24 Weeks to Investigate the Radiological Onset of Action After Treatment Initiation With Subcutaneous Natalizumab in Patients With Relapsing-Remitting Multiple Sclerosis (TYS-ON)
Conditions
Interventions
Trial Snapshot
- Phase
- Phase 4
- Status
- Terminated
- Sponsor
- Biogen
- Enrollment
- 1
- Locations
- 2
- Primary Endpoint
- Cumulative Number of Active Lesions (CUALs) Through Week 24
Study Overview
Brief Summary
The primary objective of this study is to evaluate the radiological efficacy of SC natalizumab over time through Week 24 in natalizumab-naïve participants, as measured by brain magnetic resonance imaging (MRI). The secondary objectives of this study are to evaluate additional lesion-related radiological efficacy measures over time, relapse-based clinical efficacy measures, disability improvement and worsening (EDSS), pharmacokinetic and pharmacodynamic parameters, the immunogenicity of repeated doses, and safety in treatment-naïve participants of SC natalizumab.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 60 Years (Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Diagnosis of RRMS according to the McDonald criteria
- •Treatment-naïve in respect to natalizumab as disease modifying monotherapy for RRMS
- •No or not more than one prior MS disease-modifying therapy
- •Highly active RRMS, as defined by at least one relapse in the previous year and at least one T1 gadolinium-enhancing lesion or ≥3 new or enlarging T2 lesions
- •EDSS score ≤ 5.5 at Screening
- •Estimated glomerular filtration rate (eGFR) >30 millilitre per min (mL/min), as estimated using the Cockcroft-Gault formula.
Exclusion Criteria
- •Primary- and secondary-progressive MS
- •Participants for whom MRI is contraindicated
- •History of any clinically significant 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
- •History of severe allergic or anaphylactic reactions or known hypersensitivity to any antibody drug therapy.
- •NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
Arms & Interventions
Natalizumab
Experimental
Participants will receive natalizumab 300 milligrams (mg) (2*150 mg), SC injection, once every 4 weeks (Q4W) up to Week 24.
Intervention: Natalizumab (Drug)
Outcomes
Primary Outcomes
Cumulative Number of Active Lesions (CUALs) Through Week 24
Time Frame: Up to Week 24
Cumulative number of active lesions will be calculated as the sum of the number of gadolinium (Gd)-enhancing lesions and new or enlarging T2 hyperintense lesions that are non-enhancing on post-gadolinium T1-weighted (T1w) scans. It is also referred to as combined unique active lesions (CUALs).
Secondary Outcomes
- Absolute Number of CUALs at Weeks 4, 8, 12, and 24(Weeks 4, 8, 12, and 24)
- Absolute Number of New or Enlarging T2 Lesions at Weeks 4, 8, 12, and 24(Weeks 4, 8, 12, and 24)
- Change From Baseline in Lymphocyte Subsets Count(Baseline up to Week 24)
- Change From Baseline in Anti-Natalizumab Antibodies(Pre dose on Baseline, Weeks 12, and 24)
- Change From Baseline of Any (New or Persisting) Gd-Enhancing Lesions at Weeks 4, 8, 12, and 24(Baseline, Weeks 4, 8, 12, and 24)
- Annualized Relapse Rate(Week 24)
- Trough Serum Natalizumab Concentration (Ctrough)(Pre dose on Baseline, Weeks 4, 8, 12, and 24)
- Cumulative Number of New or Enlarging T2 Lesions at Weeks 4, 8, 12, and 24(Weeks 4, 8, 12, and 24)
- Change From Baseline of New or Enlarging T2 Lesions at Weeks 4, 8, 12, and 24(Baseline, Weeks 4, 8, 12, and 24)
- Cumulative Number of CUALs Through Weeks 4, 8, and 12(Weeks 4, 8, and 12)
- Mean Change From Baseline of CUALs at Weeks 4, 8, 12, and 24(Baseline, Weeks 4, 8, 12, and 24)
- Cumulative Number of New Gd-Enhancing Lesions Through Weeks 4, 8, 12, and 24(Weeks 4, 8, 12, and 24)
- Absolute Number of New Gd-Enhancing Lesions at Weeks 4, 8, 12, and 24(Weeks 4, 8, 12, and 24)
- Absolute Number of Persisting Gd-Enhancing Lesions at Weeks 4, 8, 12, and 24(Weeks 4, 8, 12, and 24)
- Absolute Number of Any (New or Persisting) Gd-Enhancing Lesions at Weeks 4, 8, 12, and 24(Weeks 4, 8, 12, and 24)
- Time to First Relapse(Up to Week 24)
- Number of Participants With Expanded Disability Status Scale (EDSS) Improvement and Stable Disease and Worsening at Weeks 12, and 24(Baseline, Weeks 12, and 24)
- Trough alpha 4 (α4) Integrin Saturation(Pre dose on Baseline, Weeks 4, 8, 12, and 24)
- Persistence of Anti-Natalizumab Antibodies(Re-test after 6 weeks of first positive result (up to Week 24))
- Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)(Up to Week 24)
Investigators
Study Sites (2)
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