Real World Effectiveness of Natalizumab Extended Interval Dosing in a French Cohort

NCT04580381 | Completed FDA Drug

• 1 other identifier: FRA-TYS-19-11504
• Study Type: observational
• Target: 500
• Locations: 1 country
• Sites: 5

Brief Summary

Natalizumab (NTZ) use in Multiple Sclerosis (MS) in highly active patients has been largely established during the last Rationale 10 years in both clinical trials and real-world practice. Along with its efficacy, NTZ use has been limited by potential risk of progressive multifocal leukoencephalopathy (PML). Thus, several studies have tried to assess how to minimize this risk. One suggested approach is to move from the standard interval dose (SID) of 4 weeks to an extended interval dose (EID) of 5 weeks or longer. Extending the dosing interval of NTZ has been practiced by some physicians with the intention of improving the benefit/risk of the treatment by reducing the exposure-dependent risk of progressive multifocal leukoencephalopathy (PML) while maintaining efficacy. We propose to retrospectively analyze data from clinical records coming from RRMS patients treated in France at 5 different centers; Caen, Nice, Bobigny and Toulouse hospitals as well as Percy Military Hospital, to evaluate the effectiveness of natalizumab EID in subjects who have previously been treated with natalizumab SID for 12 months, in relation to continued SID treatment. In the clinical practice of these centers, patients are shifted after minimum 12 months under SID to an EID of 6 weeks regardless antibody JC serum status. Clinical, magnetic resonance imaging (MRI) and serum anti-JCV antibody status data are collected when available. The objective of this study is to assess the efficacy in term of ARR and safety.

Conditions

Multiple Sclerosis, Relapsing-Remitting

Keywords

Natalizumab; Extended Interval Dosing

Outcome Measures

Primary Outcomes (1)

• Annualized Relapse Ratio

  relapse rate per patient per year

  baseline to 12 month follow-up

Secondary Outcomes (3)

• Disability progression

  baseline to 12 month follow-up

• NEDA-3 achievement

  baseline to 12 month follow-up

• Radiological activity

  baseline to 12 month follow-up

Other Outcomes (1)

• Safety outcome

  baseline to 12 month follow-up

Study Arms (2)

Standard Interval Dosing (SID)

Patients continuing Natalizumab treatment with standard interval dosing defined as \> 11 infusions per year

Drug: Natalizumab Injection [Tysabri]

Extended Interval Dosing (EID)

Patients switching to extended interval dosing defined as ≤ 10 infusions per year

Drug: Natalizumab Injection [Tysabri]

Interventions

Natalizumab Injection [Tysabri] DRUG

Natalizumab infusion interval according to local practice defining the patient's group

Extended Interval Dosing (EID); Standard Interval Dosing (SID)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Patients receiving Natalizumab as disease-modifying monotherapy for RRMS

You may qualify if:

• Patients receiving at least 11 infusions of natalizumab as disease-modifying monotherapy for RRMS that is consistent with the approved dosing

You may not qualify if:

• Patients for whom the NTZ infusion history and/or MRI and clinical history is not available.
• Patients with dosing gap defined as \>=12 weeks between any two doses.
• Patients with over dose defined as \<3 weeks between any two doses.
• Pregnancy during the follow-up period

Sponsors & Collaborators

• University Hospital, Caen: lead
• Biogen: collaborator

Study Sites (5)

Department of Neurology, CHU Bobigny-Avicenne

Bobigny, 93000, France

Location

Department of Neurology, CHU de Caen

Caen, 14000, France

Location

Department of Neurology, Percy Military Hospital

Clamart, 92140, France

Location

Department of Neurology, CHU Nice

Nice, 06000, France

Location

Department of Neurology, CHU Toulouse Purpan

Toulouse, 31300, France

Location

Related Publications (1)

• Pelle J, Briant AR, Branger P, Derache N, Arnaud C, Lebrun-Frenay C, Cohen M, Mondot L, De Seze J, Bigaut K, Collongues N, Kremer L, Ricard D, Bompaire F, Ohlmann C, Sallansonnet-Froment M, Ciron J, Biotti D, Pignolet B, Parienti JJ, Defer G. Real-World Effectiveness of Natalizumab Extended Interval Dosing in a French Cohort. Neurol Ther. 2023 Apr;12(2):529-542. doi: 10.1007/s40120-023-00440-5. Epub 2023 Feb 10.

  PMID: 36763307 DERIVED

MeSH Terms

Conditions

Multiple Sclerosis, Relapsing-Remitting

Interventions

Natalizumab

Condition Hierarchy (Ancestors)

Multiple Sclerosis; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 2, 2020
• First Posted: October 8, 2020
• Study Start: September 1, 2020
• Primary Completion: October 1, 2021
• Study Completion: October 30, 2021
• Last Updated: March 9, 2022

Record last verified: 2020-09

Data Sharing

• IPD Sharing: Will not share

Locations

FR (5)