Personalized Extended Interval Dosing of Natalizumab in Relapsing Remitting Multiple Sclerosis
SUPERNEXT
1 other identifier
interventional
300
1 country
24
Brief Summary
Rationale: Natalizumab is an effective drug in the treatment for relapsing remitting multiple sclerosis (RRMS) and is approved by de FDA/EMA in a 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. A recent randomized controlled trial (RCT) suggests natalizumab maintains a high level of effi-cacy in stable patients with RRMS switching to a 6 week interval. Our study group demon-strated 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 compli-cations of natalizumab treatment. Objective: Our objective is to test feasibility and validate safety of personalized extended interval dosing of natalizumab starting from 6 weeks 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: All patients currently included in the NEXT-MS trial will receive an adjusted personalized extended interval dosing treatment regimen of natalizumab based on natalizumab concentrations starting from an infusion interval of 6 weeks. Main study parameters/endpoints: Our 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 JC virus conversion, JC virus index, incidence of progressive multifocal leukoencephalopathy, treatment satisfaction and quality of life. The influence of personalized dosing on pharmacokinetics will be monitored.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_4
Started Feb 2020
Longer than P75 for phase_4
24 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 3, 2020
CompletedFirst Posted
Study publicly available on registry
January 13, 2020
CompletedStudy Start
First participant enrolled
February 3, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 1, 2025
CompletedStudy Completion
Last participant's last visit for all outcomes
March 1, 2025
CompletedApril 27, 2023
April 1, 2023
5.1 years
January 3, 2020
April 25, 2023
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Change of T2 lesions on brain MRI
Assessing new/enlarging T2 lesions on brain MRI
Baseline, year 1, year 2
Secondary Outcomes (13)
Annualized relapse rate
Baseline, year 1, year 2
Disability progression during follow-up
Baseline, year 1, year 2
Cost analysis
Baseline, year 1, year 2
JC virus conversion
6 monthly JCV measurement for two years
Course JC virus index
6 monthly JCV measurement for two years
- +8 more secondary outcomes
Study Arms (3)
Personalized extended interval dosing
EXPERIMENTALPatients will be receiving a personalized dosing schedule from 6 weeks, which will be further extended if the trough level exceeds 10 ug/ml.
Standard interval dosing
OTHERPatients who prefer to stay on standard interval dosing.
Historic cohort
OTHERHistoric cohort of natalizumab treated patients on standard interval dosing.
Interventions
Personalized extended interval dosing of natalizumab with a schedule from every 6 weeks, which will be further extended if the trough level exceeds 10 ug/ml.
Standard interval dosing in control group and historic group
Eligibility Criteria
You may qualify if:
- Diagnosis of relapsing remitting multiple sclerosis according to the 2017 criteria
- or more consecutive natalizumab infusions
- years or older
- Agreed to participate (written informed consent)
You may not qualify if:
- 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)
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Amsterdam UMC, location VUmclead
- Stichting MS Researchcollaborator
- Innovatiefonds Zorgverzekeraarscollaborator
- Stichting Treatmedscollaborator
Study Sites (24)
Jeroen Bosch Hospital
's-Hertogenbosch, Netherlands
Ziekenhuisgroep Twente hospital
Almelo, Netherlands
Flevoziekenhuis
Almere Stad, Netherlands
Amsterdam UMC, location VUmc
Amsterdam, Netherlands
OLVG
Amsterdam, Netherlands
Rijnstate Hospital
Arnhem, Netherlands
Wilhelmina hospital Assen
Assen, Netherlands
Amphia Hospital
Breda, Netherlands
Reinier de Graaf hospital
Delft, Netherlands
Slingeland Hospital
Doetinchem, Netherlands
Ommelander Hospital Groningen
Groningen, Netherlands
University Medical Center Groningen
Groningen, Netherlands
Spaarne gasthuis hospital
Haarlem, Netherlands
Sint-Jansdal Hospital
Harderwijk, Netherlands
Medisch Centrum Leeuwarden
Leeuwarden, Netherlands
Alrijne Hospital
Leiden, Netherlands
Maasstad hospital
Maastricht, Netherlands
Canisius Wilhelmina Hospital
Nijmegen, Netherlands
Erasmus Medical Center
Rotterdam, Netherlands
Haaglanden Medical Center
The Hague, Netherlands
Elizabeth tweesteden Hospital
Tilburg, Netherlands
Diakonessenhuis
Utrecht, Netherlands
St. Antonius Hospital
Utrecht, Netherlands
Isala
Zwolle, Netherlands
Related Publications (2)
Foley JF, Defer G, Ryerson LZ, Cohen JA, Arnold DL, Butzkueven H, Cutter G, Giovannoni G, Killestein J, Wiendl H, Smirnakis K, Xiao S, Kong G, Kuhelj R, Campbell N; NOVA study investigators. Comparison of switching to 6-week dosing of natalizumab versus continuing with 4-week dosing in patients with relapsing-remitting multiple sclerosis (NOVA): a randomised, controlled, open-label, phase 3b trial. Lancet Neurol. 2022 Jul;21(7):608-619. doi: 10.1016/S1474-4422(22)00143-0. Epub 2022 Apr 25.
PMID: 35483387BACKGROUNDToorop AA, van Lierop ZY, Gelissen LM, Hoitsma E, Zeinstra EM, van Rooij LC, van Munster CE, Vennegoor A, Mostert JP, Wokke BH, Kalkers NF, Hoogervorst EL, van Eijk JJ, Roosendaal CM, Kragt JJ, Eurelings M, van Genugten J, Nielsen J, Sinnige L, Kloosterziel ME, Arnoldus EP, van Dijk GW, Bouvy WH, Wessels MH, Boonkamp L, Strijbis EM, van Oosten BW, De Jong BA, Lissenberg-Witte BI, Barkhof F, Moraal B, Teunissen CE, Rispens T, Uitdehaag BM, Killestein J, van Kempen ZL. Prospective trial of natalizumab personalised extended interval dosing by therapeutic drug monitoring in relapsing-remitting multiple sclerosis (NEXT-MS). J Neurol Neurosurg Psychiatry. 2024 Apr 12;95(5):392-400. doi: 10.1136/jnnp-2023-332119.
PMID: 37963723DERIVED
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Design
- Study Type
- interventional
- Phase
- phase 4
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Principal investigator
Study Record Dates
First Submitted
January 3, 2020
First Posted
January 13, 2020
Study Start
February 3, 2020
Primary Completion
March 1, 2025
Study Completion
March 1, 2025
Last Updated
April 27, 2023
Record last verified: 2023-04