To assess the effect of teriflunomide in comparison to placebo, on frequency of multiple sclerosis (MS) relapses in patients with relapsing forms of MS who are treated with interferon beta (IFN-β)
ID
Source
Brief title
Condition
- Demyelinating disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Annualized relapse rate, defined as number of relapses per patientyear.
Secondary outcome
Key secondary endpoints:
• Brain MRI measure of number of gadolinium enhancing (Gdenhancing)
T1-weighted hypointense lesions (T1)-lesions.
• Time to disability progression.
Background summary
Multiple sclerosis (MS) is an inflammatory condition that damages the myelin of
the central nervous system resulting in neurological impairment and,
frequently, severe disability. It is the most frequent cause of disability in
young adults, after car accidents. The disease affects
approximately 2.5 million people worldwide at an incidence of 7 in 100
000/year. The following disease-modifying drugs are approved for the treatment
of MS: Avonex (interferon beta-1a), Betaseron or Extavia (interferon beta-1b),
Copaxone (glatiramer acetate), Rebif (interferon beta-1a), Novantrone
(mitoxantrone), and Tysabri®. Interferon beta (IFN-β) has been used as first
line disease-modifying drug in the treatment of
RMS for more than a decade. However it is only partially effective, as most
patients continue to have clinical relapses even while under treatment. Some
patients remain on IFN-β since they perceive the treatment to be somewhat
beneficial, even though it does not completely control disease activity. In
these cases, the patients could benefit from having a tighter control on their
disease, and one option is to use an adjunct therapy to improve efficacy.
Therefore, the purpose of this study is to assess the efficacy and safety of 7
mg and 14 mg of teriflunomide in comparison to the placebo in patients with
relapsing MS who are treated with IFN-β.
Study objective
To assess the effect of teriflunomide in comparison to placebo, on frequency of
multiple sclerosis (MS) relapses in patients with relapsing forms of MS who are
treated with interferon beta (IFN-β)
Study design
Approximately 1455 patienten will be randomized in 3 parallel groups of
terflunomide 7 mg, teriflunomide 14 mg and placebo on top IFN-β based on a
1:1:1 randomization ration . Teriflunomide and placebo are double-blind. The
treatment duration is
approximately 48 weeks for the last patient recruited.
Intervention
Patients treated with IFN-β will be randomized in the placebo-, teriflunomide 7
mg or teriflunomide 14 mg arm. Patients will use the teriflunomide or placebo
till the end of the trial or untill treatment discontinuation.
Study burden and risks
The common side effects reported in patients taking teriflunomide during
clinical studies are nasopharyngitis (upper respiratory infection), flu
symptoms, hair thinning/loss, nausea, elevated liver function test, paresthesia
and hypoesthesia (abnormal skin sensations like numbness and tingling), pain
(limb, joint or back), diarrhea, constipation, rash, and abdominal pain. An
increase in blood pressure (usually mild) may occur. Blood tests have shown a
mild decrease in the number of white blood cells but are not common.
Teriflunomide may reduce your immune defense, which may increase susceptibility
to infections.
Side effects reported for cholestyramine commonly include: constipation,
stomach pain, nausea, diarrhea, heartburn or indigestion, abdominal gas,
vomiting, belching, dizziness, and headache; and rarely include: bleeding
tendencies, and weight loss. Side effects for activated charcoal include
black stools, nausea and constipation.
Kampenringweg 45- E
Gouda 2803 PE
NL
Kampenringweg 45- E
Gouda 2803 PE
NL
Listed location countries
Age
Inclusion criteria
Patient with relapsing forms of multiple sclerosis (MS) treated with Interferon beta (IFN-β) defined by:
- Stable dose of IFN-β for at least 6 months prior to randomization,and
- Disease activity in the 12 months prior to randomization and after first 3 months of IFN-β treatment (at least one relapse supported by Expanded Disability status Scale (EDSS) or equivalent neurological examination, or, at least one brain or spinal cord Magnetic Resonance Imaging (MRI) with at least one T1 gadolinium enhancing lesion).
Exclusion criteria
< 18 years of age or >= 56 years of age.
McDonald*s criteria for MS diagnosis not met at time of screening visit.
EDSS score > 5.5 at randomization visit.
A relapse within 30 days prior randomization.
Human Immunodeficiency Virus (HIV) positive patient.
Prior use within 6 months preceding randomization or concomitant use of nataluzimab and any other immunosuppressant agents such as azathioprine, cyclophosphamide, cyclosporin, methotrexate, mycophenolate or fingolimod.
Prior use in the 3 months preceding randomization of cytokine therapy (except baseline IFN-β), glatiramer acetate or intravenous immunoglobulins, or concomitant use of these treatments.
Prior use within 2 years preceding randomization or concomitant use of cladribine and mitoxantrone.
Pregnant or breast-feeding women or those who plan to become pregnant during the study.
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 | EUCTR2010-023172-12-NL |
| CCMO | NL34295.060.10 |
| Other | Zie sectie J. |