PDNMS: Towards Personalized Dosing of Natalizumab in Multiple Sclerosis

Sponsor

Amsterdam UMC, location VUmc (Other)

Overall Status

Completed

CT.gov ID

NCT03516526

Collaborator

Prothya Biosolutions (Industry), Erasmus Medical Center (Other), St. Antonius Hospital (Other), OLVG (Other), Rijnstate Hospital (Other)

Enrollment

Locations

Arm

31.9

Actual Duration (Months)

12.2

Patients Per Site

0.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Multiple Sclerosis	Drug: Natalizumab	Phase 4

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 Design

Study Type:

Interventional

Actual Enrollment :

61 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Towards Personalized Dosing of Natalizumab in Multiple Sclerosis

Actual Study Start Date :

Nov 3, 2016

Actual Primary Completion Date :

Jun 21, 2019

Actual Study Completion Date :

Jul 1, 2019

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Gadolinium enhancing T1 lesions on brain MRI [12 months]
Occurrence and number of gadolinium enhancing T1 lesions of brain MRI

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	Country
1	OLVG	Amsterdam	Netherlands
2	VU medical center	Amsterdam	Netherlands
3	Rijnstate Hospital	Arnhem	Netherlands
4	Erasmus medical center	Rotterdam	Netherlands
5	St. Antonius Hospital	Utrecht	Netherlands

Sponsors and Collaborators

Amsterdam UMC, location VUmc
Prothya Biosolutions
Erasmus Medical Center
St. Antonius Hospital
OLVG
Rijnstate Hospital

Investigators

Principal Investigator: Joep Killestein, Dr., Amsterdam UMC, location VUmc

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Zoé van Kempen, Coordinating investigator, Amsterdam UMC, location VUmc

ClinicalTrials.gov Identifier:

NCT03516526

Other Study ID Numbers:

NL56584.029.16

First Posted:

May 4, 2018

Last Update Posted:

Jul 12, 2019

Last Verified:

Jul 1, 2019

Individual Participant Data (IPD) Sharing Statement:

Undecided

Plan to Share IPD:

Undecided

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Product Manufactured in and Exported from the U.S.:

Keywords provided by Zoé van Kempen, Coordinating investigator, Amsterdam UMC, location VUmc

natalizumab

Additional relevant MeSH terms:

Multiple Sclerosis

Sclerosis

Natalizumab

Study Results

No Results Posted as of Jul 12, 2019