Assignment 2010). 2. AIM OF THE STUDY The aim

Assignment B3: Clinical
Development Phase III

 

1. USED ARTICLE
The used article is ”Oral Fingolimod or Intramuscular Interferon for Relapsing
Multiple Sclerosis” (Cohen & Barkhof, 2010).

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2. AIM OF THE STUDY
The aim of the study
is to evaluate the efficacy, safety and tolerability of oral fingolimod
compared with intramuscular interferon during a 12-month observation

·        
Indication area and reference drug
The indication area
is Relapsing Remitting Multiple Sclerosis (RRMS). The reference drug is interferon
beta-1a (Avonex)

·        
The intended therapeutic action of the study
drug
Oral fingolimod prevents normal lymphocyte egress from lymphoid tissues, thus
reducing the infiltration of autoaggressive lymphocytes into the Central
Nervous System (CNS), where they would cause inflammation and tissue damage. This
action of fingolimod is primarily mediated by modulation of sphingosine-1-phosphate-receptor
1 (S1P1). An oral treatment option for RRMS is also highly desirable by
patients.

3. THE PHARMACOLOGICAL OR BIOLOGICAL MECHANISM
OF ACTION OF THE REFERENCE DRUG
Interferon beta-1a intramuscular
injection is used to reduce the number of episodes of symptoms and slow the
development of disability in patients with RRMS. It is a immunomodulator. It is
not known how interferon beta-1a works to treat MS.

4. CLINICAL ENDPOINTS
The primary efficacy end point was the Annualized Relapse Rate (ARR),
which was defined as the number of confirmed relapses during a 12-month period.
The two key secondary end points were the number of new or enlarged
hyperintense lesions on T2-weighted MRI scans at 12 months and the
time to confirmed disability progression.

5. STUDY DESIGN
It is a
12-month, phase 3, multicentre, randomized, double-blind, double dummy,
parallel-group study. Randomization was performed centrally in blocks of six
within each site and was stratified according to site. During the trial,
patients, study personnel, MRI evaluators, steering-committee members, and the
study statistician were unaware of study-group assignments and leukocyte
counts. Capsules, syringes, and packaging materials for active and placebo
treatments were indistinguishable. Patients were instructed to cover injection
sites at visits and not to discuss adverse events with clinical evaluators. An
independent physician monitored patients after the first dose of the oral study
drug was administered. Employees of the sponsor working independently of the
study team monitored first-dose safety data. An independent data and safety
monitoring board evaluated overall safety in the fingolimod phase 3 program.

 

·        
Characteristics and numbers of subjects

Inclusion criteria:

o  
Aged between 18 and 55 years.

o  
Diagnosed with RRMS

o  
Had at least one documented relapse during
previous year or at least two during previous 2 years.

o  
A score of 0 to 5.5 on the Expanded Disability
Status Scale (EDSS).

Exclusion criteria:

o  
A documented relapse or corticosteroid
treatment within 30 days before randomization

o  
Active infection

o  
Macular edema

o  
History with immunosuppressive drugs

o  
Clinically significant coexisting systemic
disease

 

A total of 1280 patients
enrolled the study.

 

·        
Duration of the study
The duration of the
study is 12 months.

·        
Time of measuring clinical endpoints

o  
Primary endpoint: The ARR are measured during a period of 12 months
throughout the treatment with fingolimod or interferon beta-1a  

o  
Secondary endpoint 1: MRI scans are obtained at
screening and at 12 months.

o  
Secondary endpoint 2: The time to confirmed disability
progression are measured during a period of 12 months. EDSS scores are determined
every 3 months

·        
The considerations for dosages and route of
administration of the study drug
The route of
administration of the study drug is oral, with a daily dose of either 1.25 or
0.5 mg.

·        
Route and dose of reference drug
The route of the
reference drug is intramuscular, with weekly dose of 30g.

·        
Which medical centers were involved?
A total of 172 clinical
centers in 18 countries were involved.

6. RESULTS OF THE CLINICAL STUDY
A total of 1153 patients completed the study.

·        
Relapse rates:
There was a significantly greater reduction of the ARR in both fingolimod
groups. Relapse-related measures also significantly favoured fingolimod .The ARR
for fingolimod 0.5mg was 0.16 and the ARR for interferon beta-1a was 0.33
(P