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Clinical Disease Activity With Long Term Natalizumab Treatment

Completed
Conditions
Relapsing-Remitting Multiple Sclerosis
Interventions
Registration Number
NCT02677077
Lead Sponsor
Biogen
Brief Summary

The primary objective of the study is to retrospectively investigate the proportion of participants free of new or enlarging fluid-attenuated inversion recovery (FLAIR) lesions over time in approximately 300 Relapsing-Remitting Multiple Sclerosis (RRMS) participants with regular MRI follow-up, who have received natalizumab ≥24 month from two different observational cohorts: 1) approximately 230 participants from the Czech Republic; and 2) approximately 70 participants from Belgium. The secondary objectives of this study are as follows: Brain volume change by various measures; Changes in the number and volume of magnetic resonance imaging (MRI) lesions; No evidence of disease activity (NEDA) with and without brain volume change.

Detailed Description

Natalizumab will not be provided to participants by Biogen as a part of this study. Participants will remain on natalizumab therapy as prescribed by their physician.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
277
Inclusion Criteria
  • Diagnosis of RRMS.
  • Continuous treatment with natalizumab of ≥24 months. In case of a treatment interruption from natalizumab ≥60 days after a total treatment period of ≥24 months, only the treatment prior to the interruption will be analyzed. Any data after this treatment interruption (even if the patient restarts natalizumab) will not be analyzed/collected.
  • ≥1 MRI scan of sufficient quality for reliable measurement.
  • Baseline MRI scan ≤6 month prior to natalizumab treatment acquired.
  • ≥1 MRI scan of sufficient quality for reliable measurement taken while on natalizumab treatment for ≥6 months.
  • EDSS ≤ 6.5.

Key

Exclusion Criteria
  • Anti-natalizumab antibody detection.
  • Prior treatment with alemtuzumab.
  • Prior treatment with mitoxantrone within 12 months of the first infusion of natalizumab.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
BelgiumnatalizumabApproximately 70 participants with RRMS receiving commercial natalizumab in Belgium
Czech RepublicnatalizumabApproximately 230 participants with RRMS receiving commercial natalizumab in Czech Republic
Primary Outcome Measures
NameTimeMethod
Change over time in the number of participants free of new or enlarging FLAIR lesionsTreatment years 3 and 4

Lesions that are ≥5 mm per scan (slice thickness 3 mm) as assessed by semiautomatic lesion count (by the Icometrix algorithm).

Secondary Outcome Measures
NameTimeMethod
Annualized T1-hypointense and FLAIR lesion volume changePost long term treatment with natalizumab (>2 years) through Year 4
Annualized brain volume change rate as assessed by percent brain volume change [PBVC]Post long term treatment with natalizumab (>2 years) through Year 4
Annualized brain volume change rate as assessed by % change in brain parenchymal fraction [BPF]Post long term treatment with natalizumab (>2 years) through Year 4
Annualized brain volume change rate as assessed by white matter [WM] and gray matter [GM] atrophy)Post long term treatment with natalizumab (>2 years) through Year 4
Cumulative number of new ≥6-month confirmed T1-hypointense lesionsPost long term treatment with natalizumab (>2 years) through Year 4
Number of participants with brain volume loss ≤0.2% and ≤0.4%Post long term treatment with natalizumab (>2 years) through Year 4
Cumulative percent change in T1-hypointense and FLAIR lesion volumePost long term treatment with natalizumab (>2 years) through Year 4
Cumulative number of ≥6-month-confirmed T1-hypointense lesions arising from new on- treatment Gadolinium (Gd+)-enhancing lesionsPost long term treatment with natalizumab (>2 years) through Year 4

No relapse and no ≥6-month confirmed Expanded Disability Status Scale (EDSS) progression and no new or enlarging FLAIR lesions and no new Gd+-enhancing lesions

Number of total participants and 4-year completers with NEDA as measured by clinical measuresPost long term treatment with natalizumab (>2 years) through Year 4

No relapse and no ≥6-month confirmed EDSS progression and no new or enlarging FLAIR lesions and no new Gd+-enhancing lesions, brain volume change rate as assessed by PBVC

Number of total participants and 4-year completers with NEDA as measured by radiological measuresPost long term treatment with natalizumab (>2 years) through Year 4

No new or enlarging FLAIR lesions and no new Gd+-enhancing lesions

Trial Locations

Locations (3)

Research Site

🇨🇿

Prague, Czechia

Research Site 2

🇧🇪

Brussels, Belgium

Research Site 1

🇧🇪

Brussels, Belgium

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