Clinical trial NCT05532163: A Study to Investigate the Radiological Onset of Action After Treatment Initiation With Subcutaneous (SC) Natalizumab in Participants With Relapsing-Remitting Multiple Sclerosis (RRMS)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Multiple Sclerosis, Relapsing-Remitting
Lead sponsor: Biogen
Sponsor class: INDUSTRY
First posted: 2022-09-08
Enrollment: 1
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: Key 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.

Key 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.

Primary outcomes:
measure: Cumulative Number of Active Lesions (CUALs) Through Week 24
timeFrame: Up to Week 24
Secondary outcomes:
measure: Cumulative Number of CUALs Through Weeks 4, 8, and 12
timeFrame: Weeks 4, 8, and 12
measure: Absolute Number of CUALs at Weeks 4, 8, 12, and 24
timeFrame: Weeks 4, 8, 12, and 24
measure: Mean Change From Baseline of CUALs at Weeks 4, 8, 12, and 24
timeFrame: Baseline, Weeks 4, 8, 12, and 24
measure: Cumulative Number of New Gd-Enhancing Lesions Through Weeks 4, 8, 12, and 24
timeFrame: Weeks 4, 8, 12, and 24
measure: Absolute Number of New Gd-Enhancing Lesions at Weeks 4, 8, 12, and 24
timeFrame: Weeks 4, 8, 12, and 24
measure: Absolute Number of Persisting Gd-Enhancing Lesions at Weeks 4, 8, 12, and 24
timeFrame: Weeks 4, 8, 12, and 24
measure: Absolute Number of Any (New or Persisting) Gd-Enhancing Lesions at Weeks 4, 8, 12, and 24
timeFrame: Weeks 4, 8, 12, and 24
measure: Change From Baseline of Any (New or Persisting) Gd-Enhancing Lesions at Weeks 4, 8, 12, and 24
timeFrame: Baseline, Weeks 4, 8, 12, and 24
measure: Cumulative Number of New or Enlarging T2 Lesions at Weeks 4, 8, 12, and 24
timeFrame: Weeks 4, 8, 12, and 24
measure: Absolute Number of New or Enlarging T2 Lesions at Weeks 4, 8, 12, and 24
timeFrame: Weeks 4, 8, 12, and 24
measure: Change From Baseline of New or Enlarging T2 Lesions at Weeks 4, 8, 12, and 24
timeFrame: Baseline, Weeks 4, 8, 12, and 24
measure: Annualized Relapse Rate
timeFrame: Week 24
measure: Time to First Relapse
timeFrame: Up to Week 24
measure: Number of Participants With Expanded Disability Status Scale (EDSS) Improvement and Stable Disease and Worsening at Weeks 12, and 24
timeFrame: Baseline, Weeks 12, and 24
measure: Trough Serum Natalizumab Concentration (Ctrough)
timeFrame: Pre dose on Baseline, Weeks 4, 8, 12, and 24
measure: Trough alpha 4 (α4) Integrin Saturation
timeFrame: Pre dose on Baseline, Weeks 4, 8, 12, and 24
measure: Change From Baseline in Lymphocyte Subsets Count
timeFrame: Baseline up to Week 24
measure: Change From Baseline in Anti-Natalizumab Antibodies
timeFrame: Pre dose on Baseline, Weeks 12, and 24
measure: Persistence of Anti-Natalizumab Antibodies
timeFrame: Re-test after 6 weeks of first positive result (up to Week 24)
measure: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Up to Week 24
Other outcomes:
Locations:
city: Bamberg
country: Germany
facility: Neurologische Praxis Dr. med. Boris-Alexander Kallmann
city: Bonn
country: Germany
facility: Neurologische Studiengesellschaft Bonn GbR
Study officials:
References: