To document the long-term safety and tolerability of teriflunomide in MS patients with relapses.
ID
Source
Brief title
Condition
- Demyelinating disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint is the safety of teriflunomide. Safety parameters include
adverse events, Physical examinations, vital signs, blood and urine laboratory
parameters and ultra-sound image of pancreas.
Secondary outcome
The secondary endpoints are the proportion of disability free patients and
annualized MS relapse rate.
MRI variables: burden of disease defined as the total volume of T2 lesions
(primary MRI variable), number of enhanced T1 lesion, total volume of post
-gadolinium T1 hypo intense lesion (black holes), atrophy, total volume of
enhanced T1 lesions, and Z4 composite score (exploratory variable)
Background summary
A double-blind, placebo controlled efficacay study (EFC6049) of two doses of
teriflunomide (7 and 14 mg) in patients with multiple sclerosis with relapses
was ongoing. This study was extended with the LTS5050 study. This LTS6050
study was for the second time extended, until 292 weeks and will allow to
gather long-term safety information and additional efficacy information.
Study objective
To document the long-term safety and tolerability of teriflunomide in MS
patients with relapses.
Study design
International, multi-center study:
Parallel, double-blind study of two fixed doses of teriflunomide (7 and 14
mg/day), maintaining the double-blind status of the treatment in the previous
study. Patients receiving placebo in the previous EFC6049 study will be
randomized to either 7 or 14mg/day. Other patients will be blindly maintained
on treatment dose group 7 mg or 14 mg. After randomisation the treatment period
is maximal 288 weeks.
A post-treatment phase of 4 weeks is planned for all patients discontinuing
study drug, with a washout procedure.
Intervention
Patients will be randomized in two groups, one group with 7 mg teriflunomide
and one group with 14 mg teriflunomide.
Study burden and risks
The common side effects reported in patients taking teriflunomide during
clinical studies are: nasopharyngitis (upper respiratory infection), flu
symptoms, throat pain, hair thinning/loss, nausea, elevated liver function
test, headache, paresthesia (abnormal skin sensations like numbness or
tingling), hypoesthesia (diminished sensation), pain (limb, joint, or back),
diarrhea, constipation, rash, itching 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.
Teriflunomide breaks down in the body to a compound that has been shown to
cause changes in DNA (genetic material) in test tube studies. The long-term
effects of these findings in humans are unknown. However, these changes have
the possibility of contributing to cell diseases, including cancer.
Side effects of washout medication
Side effects reported for cholestyramine include as common: constipation,
stomach pain, nausea, diarrhea, heartburn or indigestion, abdominal gas,
vomiting, belching, dizziness, headache; and as rare: bleeding tendencies,
weight loss. Side effects for activated charcoal include black stools, nausea
and constipation. Charcoal may also reduce the effectiveness of other drugs
and should be taken at least 2 hours before or 1 hour after other drugs.
Kampenringweg 45 D-E
Gouda 2803 PE
NL
Kampenringweg 45 D-E
Gouda 2803 PE
NL
Listed location countries
Age
Inclusion criteria
- Patients who have completed the last study visit of the previous study (EFC6049) and do not meet criteria for treatment withdrawal;- Female patients of childbearing potential must agree to comply with the contraception requirement described in section 7.4 of the protocol.;- Female patients have demonstrated not to be pregnant by serum pregnancy test or breast feeding at the time of study entry.;- McDonald's criteria must continue to support the diagnosis of clinically definite MS (see protocol appendix A).;- An informed consent must be obtain in writing from the patient for this extension study prior to enrollment. Patients must demonstrate a willingness and ability to participate in a long term safety and efficacy trial with the opportunity to continue treatment on either 7 mg or 14 mg/day of teriflunomide under double-blind conditions, until availability of the results for study EFC6049 (HMR1726D/3001). Patients must actively refuse existing approved therapies. ;In addition a supplemental HIV-testing informed consent will be required for patients who have not yet signed it in the main study (EFC6049) in order to have an HIV testing at baseline and yearly.
Exclusion criteria
- Patients who do not complete the EFC6049 (HMR1726D/3001) study.;- Patients who developed clinically relevant cardiovascular, hepatic, endocrine, or other major systematic disease making implementation of the protocol or interpretation of the study results difficult or that would put the patient at risk by participing in the study.;- Any known condition or circumstance that would prevent in the investigator's opinion, compliance or completion of the study.;- Pregnancy;- Breast-feeding;- Women of child-bearing potential, except if they satisfy all conditions described in protocol section7.4.;- Patients wishing to parent children during the course of the trial, or following the trial except if they agree to follow the appropriate drug washout procedure when they stop their study participation (protocol section 10.2);- Patients requiring treatment during the study period with drugs not permitted by the study protocol (Protocol section 8.9.2);- Prior use within 4 weeks before randomization or concomitant use of cholestyramine and/or activated charcoal;- Patients with a history of recent and clinically significant drug or alcohol abuse;- Liver function impairment or persisting ALT or direct bilirubin elevations of more than 1.5-fold the upper limit of normal;- Mental conditions rendering the patient unable to understand the nature, scope and possible consequence of 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 | EUCTR2006-003361-14-NL |
| ClinicalTrials.gov | NCT00134563 |
| CCMO | NL21148.040.07 |