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Personalized Extended Interval Dosing of Natalizumab in Relapsing Remitting Multiple Sclerosis (NEXT-MS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04225312
Recruitment Status : Recruiting
First Posted : January 13, 2020
Last Update Posted : May 19, 2020
Sponsor:
Collaborators:
Stichting MS Research
Innovatiefonds Zorgverzekeraard
Information provided by (Responsible Party):
Zoé van Kempen, VU University Medical Center

Brief 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.


Condition or disease Intervention/treatment Phase
Relapsing Remitting Multiple Sclerosis Drug: Personalized extended interval dosing of natalizumab Drug: Standard interval dosing Phase 4

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 300 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Prospective national phase IV natalizumab cohort study
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Personalized Extended Interval Dosing of Natalizumab in Relapsing Remitting Multiple Sclerosis
Actual Study Start Date : February 3, 2020
Estimated Primary Completion Date : January 2, 2023
Estimated Study Completion Date : January 2, 2024

Resource links provided by the National Library of Medicine

Drug Information available for: Natalizumab

Arm Intervention/treatment
Experimental: Personalized extended interval dosing
Personalized dosing based on natalizumab trough concentration with an aim of natalizumab trough concentration of 10mcg/ml.
Drug: Personalized extended interval dosing of natalizumab
Personalized extended interval dosing of natalizumab based on natalizumab trough concentration

Experimental: Personalized longer extended interval dosing
Personalized dosing based on natalizumab trough concentration with an aim of natalizumab trough concentration of 5mcg/ml.
Drug: Personalized extended interval dosing of natalizumab
Personalized extended interval dosing of natalizumab based on natalizumab trough concentration

Standard interval dosing
Patients who prefer to stay on standard interval dosing.
Drug: Standard interval dosing
Standard interval dosing in control group and historic group

Historic cohort
Historic cohort of natalizumab treated patients on standard interval dosing.
Drug: Standard interval dosing
Standard interval dosing in control group and historic group




Primary Outcome Measures :
  1. Change of T2 lesions on brain MRI [ Time Frame: Baseline, year 1, year 2 ]
    Assessing new/enlarging T2 lesions on brain MRI


Secondary Outcome Measures :
  1. Annualized relapse rate [ Time Frame: Baseline, year 1, year 2 ]
    Clinical relapses during personalized extended interval dosing

  2. Disability progression during follow-up [ Time Frame: Baseline, year 1, year 2 ]
    Disability progression measured on the Expanded Disability Status Scale (EDSS); running form 0 (no disability) to 10 (death)

  3. Cost analysis [ Time Frame: Baseline, year 1, year 2 ]
    Cost-utility analysis using EuroQol 5D (EQ-5D) and the Work Productivity and Activtiy Impairment Questionnaire (WPAI).

  4. JC virus conversion [ Time Frame: 6 monthly JCV measurement for two years ]
    Annual conversion rate of the John Cunningham Virus (JCV)

  5. Course JC virus index [ Time Frame: 6 monthly JCV measurement for two years ]
    Course of John Cunningham Virus (JCV) index in JCV positive patients

  6. Natalizumab wearing-off effect [ Time Frame: Baseline, year 1, year 2 ]
    Occurrence of the natalizumab wearing-off effect

  7. Stability of natalizumab trough concentration [ Time Frame: 6 monthly natalizumab trough concentrations for two years ]
    Long-term stability of natalizumab trough concentration in personalized interval dosing

  8. Patient preference [ Time Frame: Baseline ]
    Percentage of patients preferring personalized treatment over standard treatment and percentage staying on personalized treatment

  9. Quality of life: MSIS-29 [ Time Frame: Baseline, year 1, year 2 ]
    Quality of life on the Multiple Sclerosis Impact Scale (MSIS-29)

  10. Satisfaction of treatment: TSQM [ Time Frame: Baseline, year 1, year 2 ]
    Satisfaction of treatment on the Treatment Satisfaction Questionnaire of Medication (TSQM)

  11. Progressive multifocal leukoencephalopathy [ Time Frame: Trough study completion, an average of 2 years ]
    Incidence of progressive multifocal leukoencephalopathy



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04225312


Contacts
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Contact: Joep Killestein 0031 0204441982 j.killestein@amsterdamumc.nl
Contact: Zoé van Kempen 0031 0204442182 z.vankempen@amsterdamumc.nl

Locations
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Netherlands
OLVG Not yet recruiting
Amsterdam, Netherlands
Contact: Nynke Kalkers, Dr       n.f.kalkers@olvg.nl   
VU medical center Recruiting
Amsterdam, Netherlands
Contact: Joep Killestein       j.killestein@amsterdamumc.nl   
Rijnstate Hospital Not yet recruiting
Arnhem, Netherlands
Contact: Jop Mostert, Dr       jmostert@rijnstate.nl   
Amphia Hospital Not yet recruiting
Breda, Netherlands
Contact: van Munster       CvanMunster@amphia.nl   
Jeroen Bosch Hospital Not yet recruiting
Den Bosch, Netherlands
Contact: van Eijk       J.Eijkvan@jbz.nl   
Medisch Centrum Haaglanden Not yet recruiting
Den Haag, Netherlands
Contact: Berger-Plantinga       e.bergerplantinga@haaglandenmc.nl   
Slingeland Hospital Not yet recruiting
Doetinchem, Netherlands
Contact: Roosendaal       C.Roosendaal@slingeland.nl   
Ommelander Hospital Groningen Not yet recruiting
Groningen, Netherlands
Contact: Nielsen       j.nielsen@ozg.nl   
University Medical Center Groningen Not yet recruiting
Groningen, Netherlands
Contact: Heersema       d.j.heersema@umcg.nl   
Canisius Wilhelmina Hospital Not yet recruiting
Nijmegen, Netherlands
Contact: van Dijk       g.v.dijk@cwz.nl   
Erasmus Medical Center Not yet recruiting
Rotterdam, Netherlands
Contact: Wokke       b.wokke@erasmusmc.nl   
Elizabeth tweesteden Hospital Not yet recruiting
Tilburg, Netherlands
Contact: Arnoldus       e.arnoldus@etz.nl   
Diakonessenhuis Not yet recruiting
Utrecht, Netherlands
Contact: Bouvy       wbouvy@diakhuis.nl   
St. Antonius Hospital Not yet recruiting
Utrecht, Netherlands
Contact: Erwin Hoogervorst, Dr       e.hoogervorst@antoniusziekenhuis.nl   
Isala Not yet recruiting
Zwolle, Netherlands
Contact: Zeinstra       ZEINSTRAE@isala.nl   
Sponsors and Collaborators
VU University Medical Center
Stichting MS Research
Innovatiefonds Zorgverzekeraard
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Responsible Party: Zoé van Kempen, Principal investigator, VU University Medical Center
ClinicalTrials.gov Identifier: NCT04225312    
Other Study ID Numbers: NL70503.029.19
First Posted: January 13, 2020    Key Record Dates
Last Update Posted: May 19, 2020
Last Verified: May 2020

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Zoé van Kempen, VU University Medical Center:
Natalizumab
Extended interval dosing
Additional relevant MeSH terms:
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Multiple Sclerosis
Multiple Sclerosis, Relapsing-Remitting
Sclerosis
Pathologic Processes
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Natalizumab
Immunologic Factors
Physiological Effects of Drugs