A multinational, multicenter, single visit, exploratory pharmacogenetic trial and long-term follow-up of the PRISMS (Prevention of Relapses and Disability by Interferon beta-1a Subcutaneously in Multiple Sclerosis) trial

This is a Phase IV, interventional, multinational, multicenter, long-term
follow-up, single visit, exploratory pharmacogenetic trial involving subjects
who previously participated in the PRISMS trial. The PRISMS study (6789) took
place 15 years ago and subsequently a follow-up study (PRISMS LTFU 22930,
Long-Term Follow-Up) was performed 8 years later to assess long-term efficacy
and safety.

Primary objective:
* To analyze the association between single nucleotide polymorphisms (SNP)
markers and treatment response. Treatment response is based on the Expanded
Disability Status Scale (EDSS) progression and relapse outcomes over the first
2 years of treatment in the PRISMS trial.

Secondary objectives:
* To assess disease progression in subjects over the long term (14-15 years
after initial randomization).
* To assess long term immunogenicity.

Tertiary objectives:
* To analyze the association between genetic markers with responses to
treatment over 2, 4, 7-8 years and 15-16 years after the initial randomization
for efficacy parameters
* To analyze the association between genetic markers with responses to
treatment over 2, 4, 6 and 7-8 years after initial randomization for safety
parameters
* To explore the association between genetic biomarkers and other possible
prognostic indicators

To address the trial objectives, a single visit will be performed. Subjects
originally randomized in the PRISMS trial (560 subjects) will be recalled for
this single visit, where possible. During the visit, medical and treatment
history from the final visit of the PRISMS trial 6789 or the PRISMS LTFU 22930
will be retrospectively collected and a medical assessment and a blood
collection for pharmacogenetics (PGx) analysis and immunogenicity assessment
will be performed.

This trial will consist of a single visit.

the following assessments will be performed:
* Medical examination:
* Multiple sclerosis (MS) history and MS treatment history review
* Neurological examination, including the EDSS score
* Blood sampling for:
* Genetic markers
* BAbs/NAbs
For safety reasons, subjects will be kept under observation for 30 minutes
after blood sampling has been performed.

New scientific knowledge and technologies have become available, which were not
available fifteen years ago, at the time the initial PRISMS study occured. In
particular, great advances have been made in human genomics and technologies
with the completion of the Human Genome Project and HapMap Project. 15 years
after the initial PRISMS study, Merck-Serono has made significant progress in
the understanding of the clinical and biological effects of Rebif. About 40% of
subjects could potentially benefit from more efficient treatment. The present
study will help understanding the molecular basis underlying the response to
Rebif while involving very minor risks or burden for the patients, who will
undergo a single visit and single blood sampling without changing their current
treatment.
Risks;
The needle sticks may cause local pain, bruising, swelling, lightheadedness,
dizziness and rarely, fainting and/or a possible infection from the needle
stick.