Personalized Extended Interval Dosing of Natalizumab in Relapsing Remitting Multiple Sclerosis

• Status: Recruiting
• Trial end date: 2024-01-01
• Target enrollment: 0
• Participant gender: All

Summary

Rationale: Natalizumab is an effective drug in the treatment for relapsing remitting multiple sclerosis (RRMS) and is approved in the treatment regimen of 4-weekly 300mg natalizumab infusions. Natalizumab trough concentrations after a 4-weekly interval are high in the large majority of patients which implies a relative overdose in most patients. The investigators have demonstrated that efficacy of natalizumab is maintained when the infusion interval is extended based on natalizumab trough concentrations (personalized extended interval dosing). This leads to fewer hospital visits, a decrease of healthcare costs and decrease of risk of complications of natalizumab treatment.

Objective: The objective is to test feasibility and validate safety of personalized extended interval dosing of natalizumab in a large real-life cohort across the Netherlands.

Study design: Prospective national phase IV natalizumab cohort study.

Study population: All patients, aged 18 years or older, who are currently treated with natalizumab in the Netherlands for RRMS, with a minimum of 6 consecutive infusions.

Intervention: Patients will receive a personalized extended interval dosing (4-8 weeks) based on two natalizumab trough concentrations in the standard 4 week interval.

Main study parameters/endpoints: The main study endpoint is the safety (defined by radiological disease activity) of personalized natalizumab dosing in a large real-life cohort across the Netherlands. Data will be collected regarding disease activity and disability progression. A cost analysis will be performed to show the extent of cost reduction. Patients will be annually followed to assess the influence of personalized dosing on John Cunningham virus (JCV) conversion, JCV index, incidence of progressive multifocal leukoencephalopathy and treatment satisfaction and quality of life. The influence of personalized dosing on pharmacokinetics will be monitored. Furthermore, personalized extended interval dosing will be studied in a subgroup with the aim to explore lower than previously studied trough values of natalizumab.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: VU University Medical Center
• Collaborators: Innovatiefonds Zorgverzekeraard; Stichting MS Research
• Treatments: Natalizumab

Criteria

Inclusion Criteria:

• Diagnosis of relapsing remitting multiple sclerosis according to the 2017 criteria21

• 6 or more consecutive natalizumab infusions

• 18 years or older

• Agreed to participate (written informed consent)

• Disease stability (radiological and clinical) ≥ 12 months (only in low personalized extended interval dosing group)

Exclusion Criteria:

• High titer natalizumab (>100 arbitrary units (AU)/ml) antibodies

• Contraindication for frequent magnetic resonance imaging (MRI) (ie, pacemaker or other contraindicated implanted metal devices, or have claustrophobia that cannot be medically managed)