Our main objective is to prove that extending dose intervals guided by serum concentrations of natalizumab, will not result in radiological or clinical disease activity.
ID
Source
Brief title
Condition
- Demyelinating disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint is the number of patients developing gadolinium (Gd+)
enhancing lesions on brain MRI.
Secondary outcome
The secondary endpoints are new or enlarging T2 lesions on brain MRI,
progression on the expanded disability status scale (EDSS) and clinical
relapses and measurements of the quality of life by the SF-36.
Background summary
Natalizumab is an efficacious second line treatment for relapsing remitting
multiple sclerosis (RRMS). Despite the knowledge of a large variation in
pharmacokinetics
and patient characteristics, treatment with natalizumab in MS is the same for
every patient with a 300mg infusion every four weeks. We believe that most
patients have natalizumab concentrations largely exceeding the threshold of
optimal efficacy just before a new infusion of natalizumab.
Study objective
Our main objective is to prove that extending dose intervals guided by serum
concentrations of natalizumab, will not result in radiological or clinical
disease activity.
Study design
A prospective multi-center, single arm trial.
Intervention
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. If serum concentration is
between 10-15µg/ml patients will remain on their current schedule. If serum
concentration drops below 10µg/ml the infusion schedule will be put back with
one week with a minimum of a four week interval between infusions.
Study burden and risks
Patients will be exposed to 3-monthly hospital visits for clinical follow-up
brain MRI scans. Patients will receive two additional MRI-scans (the normal
frequency of brain MRI is one yearly) during the study period. JC-virus
positive patients (who have chance of developing progressive mulifocal
leukoencephalopathy) are already used to this frequency of MRI-scans.
We expect that patients will receive less natalizumab infusions based on serum
concentrations. The risk of extending intervals between natalizumab infusion is
disease activity, clinically or radiologically. The risks of disease activity
is minimized by the frequent measurements of the concentration of natalizumab.
Patients will be monitored thoroughly. In case of any sign of disease activity
the dose interval will be reset to 4 weeks for the remaining study period
De Boelelaan 1118
amsterdam 1081 HZ
NL
De Boelelaan 1118
amsterdam 1081 HZ
NL
Listed location countries
Age
Inclusion criteria
- 18 years or older.
- 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 more than 15 µg/ml just prior natalizumab infusions for 2 consecutive months.
- Written informed consent.
Exclusion criteria
- Any MS disease activity (radiologically or clinically) during natalizumab treatment, with exclusion of the first three months of treatment.
- Unable to undergo frequent MRI.
- The use of other immunomodulatory medication other than natalizumab.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2016-000345-31-NL |
| CCMO | NL56584.029.16 |