Towards Personalized Dosing of Natalizumab in Multiple Sclerosis (PDNMS)

A prospective clinical trial with the aim of maintaining drug efficacy of natalizumab while extending dose intervals guided by drug concentrations in patients with relapsing remitting multiple sclerosis.

Study Overview

• Status: Completed
• Conditions: Multiple Sclerosis
• Intervention / Treatment: Drug: Natalizumab

Detailed Description

Our main objective is to prove that extending dose intervals guided by natalizumab serum concentrations, will not result in radiological or clinical disease activity in completely stable RRMS patients treated with natalizumab. Adult patients with RRMS with no evident disease activity during the last 12 months of natalizumab infusions with a minimum treatment of 12 months wil be included. Before subsequent natalizumab infusions, serum concentrations will be evaluated. If the concentration exceeds 15μg/ml the dose interval will be extended with a week to a maximum of eight weeks. Patients will get regular brain MRI scans and clinical follow-up.

• Study Type: Interventional
• Enrollment (Actual): 61
• Phase: Phase 4

Contacts and Locations

Study Locations

• Netherlands
  • Amsterdam, Netherlands
    • OLVG
  • Amsterdam, Netherlands
    • VU Medical Center
  • Arnhem, Netherlands
    • Rijnstate Hospital
  • Rotterdam, Netherlands
    • Erasmus Medical Center
  • Utrecht, Netherlands
    • St. Antonius Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Relapsing-remitting multiple sclerosis (RRMS) according to the McDonald criteria, revised by Polman 2010
• Natalizumab treatment for 12 months or longer at inclusion.
• An expanded disability status scale (EDSS) score of 0.0-6.0 at baseline.
• Natalizumab level of ≥15 μg/ml
• Written informed consent.

Exclusion Criteria:

• Any MS disease activity (radiologically or clinically) during the last 12 months of natalizumab treatment.
• Unable to undergo frequent MRI.
• The use of other immunomodulatory medication other than natalizumab.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: All patients in this study; Patients treated with natalizumab with a minimum of 1 year, without signs of disease activity (relapses, new T2 lesions on MRI) for a minimum of 1 year.	Drug: Natalizumab; Extending dose intervals of natalizumab from 4 weeks to maximum of 8 weeks based on trough natalizumab concentrations

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gadolinium enhancing T1 lesions on brain MRI	Occurrence and number of gadolinium enhancing T1 lesions of brain MRI	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
New T2 lesions on brain MRI	Occurrence and number of new T2 lesions on brain MRI	12 months
Relapses	scoring MS exacerbations	12 months
EDSS	Expanded Disability Status Scale: clinical scoring of disability in MS patients	12 months
MSFC	Multiple Status Functional Composite: clinical scoring of disability in MS patients	baseline and 12 months
patient perspective measured with the SF-36	questionnaire: Short Form-36	baseline and 12 months
patient perspective measured with the MSIS-29	questionnaire: Multiple Sclerosis Impact Scale-29	baseline and 12 months

Collaborators and Investigators

• Sponsor: Amsterdam UMC, location VUmc
• Collaborators: Erasmus Medical Center; St. Antonius Hospital; Rijnstate Hospital; OLVG; Prothya Biosolutions
• Investigators: Principal Investigator: Joep Killestein, Dr., Amsterdam UMC, location VUmc

Study record dates

Study Major Dates

• Study Start (Actual): November 3, 2016
• Primary Completion (Actual): June 21, 2019
• Study Completion (Actual): July 1, 2019

Study Registration Dates

• First Submitted: April 12, 2018
• First Submitted That Met QC Criteria: April 23, 2018
• First Posted (Actual): May 4, 2018

Study Record Updates

• Last Update Posted (Actual): July 12, 2019
• Last Update Submitted That Met QC Criteria: July 11, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Keywords: natalizumab
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Sclerosis; Physiological Effects of Drugs; Immunologic Factors; Natalizumab
• Other Study ID Numbers: NL56584.029.16

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• 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