Clinical trial NCT01134627
Conditions: Multiple Sclerosis, Relapsing-Remitting
Keywords: Multiple Sclerosis, Relapsing-Remitting Interferon-β Rebif® Minocycline
Sponsor: Merck KGaA, Darmstadt, Germany
Start date: 2006-02-01; Completion date: 2011-04-01
Enrollment: 305 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This is a multicentric, double-blind, placebo-controlled, randomized, parallel group study to estimate the effect of minocycline as add-on to interferon beta-1a (IFN beta-1a) in subjects with relapsing-remitting multiple sclerosis (RRMS).

Detailed description:
Interferon beta-1a is the approved standard therapy in RRMS. The beneficial effects of minocycline in the experimental autoimmune encephalomyelitis (EAE) model and its possible inhibitory effect on the degradation of IFN beta-1a suggest that minocycline treatment may have beneficial effects in MS as add-on therapy in subjects who are on treatment with IFN beta-1a. Adjuvant treatment with minocycline is easy to administer, well tolerated and relatively inexpensive. This is a multicentric, double blind, placebo controlled, randomized, parallel group study. Eligible subjects already started with IFN beta-1a (Rebif®) will be randomized 1:1 for treatment with either minocycline 2\*100 mg daily as add-on therapy or placebo. The subjects will be examined clinically at baseline and after 12, 24, 48, 72 and 96 weeks. Laboratory tests (hematology and clinical chemistry) will be performed at baseline and after 4, 8, 12, 24, 36, 48, 60, 72, 84 and 96 weeks (at 4, 8, 36, 60 and 84 weeks only an additional liver enzyme test will be scheduled). The MRI (T1-weighted and T2-weighted) before treatment and after 96 weeks and immunological studies before treatment and after 48 weeks will be performed in a limited number of subjects in selected centers.

OBJECTIVES

Primary Objective:

The effect of minocycline versus placebo in subjects receiving treatment with IFN beta-1a on the time to the first documented relapse

Secondary Objectives:

* To estimate the effect of minocycline versus placebo in subjects receiving treatment with IFN beta-1a on the mean number of documented relapses per subject up to year 2
* To estimate, in a limited number of 120 subjects at pre-selected sites, the effect of minocycline versus placebo in subjects receiving treatment with IFN beta-1a on the number of new or enlarging lesions on T2-weighted MRI, changes in brain volume measured on MRI

Tertiary Objectives:

* Time to onset of disability progression sustained over at least 6 months based on change from baseline in EDSS in subjects with RRMS who recently started treatment with IFN beta-1a. (Disability progression is defined as an increase of: 1.0 point on the EDSS if EDSS was \>= 1.0 at baseline; and 1.5 point on the EDSS if EDSS was 0.0 at baseline)
* Time to sustained progression by 2 points in 1 Functional System or 1 point in 2 Functional Systems
* The total number of reported relapses (documented and undocumented). An undocumented relapse is defined as the appearance of new symptoms or worsening of an old symptom, in the absence of fever, over at least 24 hours that could be attributed to MS activity, preceded by stability or improvement for at least 30 days
* The requirement for treatment with glucocorticoids due to relapses
* The time to first relapse
* The number of relapse-free (documented and undocumented relapses) subjects without progression
* The disease activity measured on the integrated disability status scale (IDSS)
* The number of subjects with a permanent loss of disability of 1.0 score on the EDSS, confirmed at 2 consecutive visits with an interval of 6 months
* The total area of MS lesions on T1 and T2-weighted MRI
* Analyze the safety with respect to the combination of Rebif® and minocycline
* Rate of dose reduction of IFN beta-1a (Rebif®)
* Relapse severity based on the EDSS and IDSS
* Immunological analyses in a limited number of subjects (MRI subgroup)
* Frequency of increase of liver enzymes according to World Health Organization (WHO) II criteria

Arms: arm 1: None arm 2: None
Interventions: intervention 1: Minocycline intervention 2: Placebo
Intervention descriptions: intervention 1: Participants who are self-administering Rebif® (IFN beta-1a) 44 microgram (mcg) as subcutaneous (sc) injection thrice weekly will also receive minocycline 100 milligram (mg) tablet twice daily as an add-on therapy in accordance with clinical practice for 96 weeks. intervention 2: Participants who are self-administering Rebif® (IFN beta-1a) 44 mcg as sc injection thrice weekly will also receive placebo tablets twice daily for 96 weeks.

Protocol documents: