Clinical Trial: Minocycline as add-on to Interferon Beta-1a [IFN Beta-1a] (Rebif®) in Relapsing-Remitting Multiple Sclerosis [RRMS]

Study Status: Terminated
Recruit Status: Terminated
Study Type: Interventional

Official Title: A Multi-centre, Double Blind, Randomized, Placebo Controlled, Parallel Group Trial Investigating Minocycline Versus Placebo as Add-on Therapy in Patients Who Are on Treatment With Interferon-beta-1a 4

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 Summary:

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
    Sponsor: Merck KGaA

    Current Primary Outcome: Number of Participants Who Experienced First Documented Relapse [ Time Frame: Baseline up to 96 weeks (+/- 1 week) or early termination (ET) ]

    Documented relapse: development of new/exacerbation of existing neurological symptoms, persisting for >48 hrs and with previous period for >30 days with stable/improving condition. Exacerbation = at least (>=)1 point increase in 2 functional systems/2 points increase in 1 system,either in pyramidal, cerebral, brain-stem, sensory, bowel and bladder, visual, cerebral or other functional system or >=0.5 point increase on expanded disability status scale (EDSS) which assesses disability in 8 functional systems with overall score ranging from 0 (normal) to 10 (death due to multiple sclerosis [MS]).


    Original Primary Outcome: Time to first relapse [ Time Frame: During the period of 2 years ]

    The median time to first relapse was recorded in days and months


    Current Secondary Outcome:

    • Number of Participants With Documented Relapses [ Time Frame: Baseline up to 96 weeks (+/- 1 week) or ET ]
      Documented relapse: development of new/exacerbation of existing neurological symptoms, persisting for >48 hrs and with previous period for >30 days with stable/improving condition. Exacerbation was >=1 point increase in 2 functional systems /2 points increase in 1 system, either in pyramidal, cerebral, brain-stem, sensory, bowel and bladder, visual, cerebral or other functional system or >=0.5 point increase on EDSS which assesses disability in 8 functional systems with overall score ranging from 0 (normal) to 10 (death due to MS).
    • Number of New or Enlarging Lesions on Time Constant 2 (T2) Weighted Magnetic Resonance Imaging (MRI) [ Time Frame: Final visit (96 weeks [+/- 1 week]) or ET ]
      Inflammatory disease activity was assessed by MRI measurement of the number of new or enlarging T2 lesions.
    • Changes in Brain Volume Measured on Magnetic Resonance Imaging (MRI) [ Time Frame: Screening , final visit (96 weeks [+/- 1 week]) or ET ]
      Changes in brain volume were measured as the brain parenchymal fraction using MRI scans.


    Original Secondary Outcome:

    • Mean number of relapses per subject [ Time Frame: During the period of 2 years ]
      A documented relapse is defined as the development of new or the exacerbation of existing neurological symptoms or signs, in the absence of fever, persisting for more than 48 hours and with a previous period for more than 30 days with a stable or an improving condition
    • Number of new or enlarging lesions on T2 weighted magnetic resonance imaging (MRI) [ Time Frame: Screening and final visit (after 96 weeks) ]
      MRI will be performed after screening and after 96 weeks in a limited number of 120 subjects in selected centers. The appearance of new lesions, enlargement of existing lesions and the total lesion load will be measured on T2 weighted scans
    • Brain atrophy [ Time Frame: After 96 weeks at final visit ]
      Brain atrophy will be measured as the brain parenchymal fraction using MRI scans measured after 96 weeks.
    • Time to confirmed progression in disability [ Time Frame: Baseline to 96 weeks ]
      Time to onset of disability progression sustained over at least six months based on change from baseline in Expanded Disbaility Statsu Scale (EDSS) in subjects with relapsing-remitting multiple sclerosis who recently started treatment with IFN-beta-1a.
    • Number of PD/T2 active lesions over Year 1 and 2 [ Time Frame: Year 1 to Year 2 ]
    • Percentage of PD/T2 Active Scans per Subject over Year 1 and Year 2 [ Time Frame: During the period of 2 years ]
    • Burden of disease [ Time Frame: Baseline to Year 2 ]
      The burden of disease (BOD) is the total area of lesions (abnormal plaques) in the brain, measured in mm2. Percentage change from baseline at Year 1 and Year 2 will be presented by treatment group.
    • Relapse count at Year 1 [ Time Frame: After first year of treatment ]
    • Relapse Free Subjects at Year 1 and Year 2 [ Time Frame: During the period of 2 years ]
    • Total number of documented and undocumented relapses [ Time Frame: During the period of 2 years ]
    • Severity of relapses [ Time Frame: During the period of 2 years ]


    Information By: Merck KGaA

    Dates:
    Date Received: May 28, 2010
    Date Started: February 2006
    Date Completion:
    Last Updated: December 2, 2013
    Last Verified: December 2013