Efficacy of Cyclophosphamide Versus Methylprednisolone in Patients With Secondary Progressive Multiple Sclerosis
Condition: Multiple Sclerosis, Chronic Progressive
MeSH terms: Multiple Sclerosis; Multiple Sclerosis, Chronic Progressive; Sclerosis
Study type: Interventional
Phase: Phase 3

Summary: 
      Preliminary not-controlled clinical studies of the efficacy of monthly intravenous
      cyclophosphamide administration in secondary progressive multiple sclerosis reported
      encouraging results, but no randomized controlled trial has been conducted so far. The
      primary objective of this trial is to evaluate the efficacy of IV cyclophosphamide as
      compared to IV methylprednisolone administered every 4 weeks during 1 year and every 8 weeks
      during 1 year, on the delay to confirmed disability deterioration as assessed by the Expanded
      Disability Status Scale (EDSS) in patients with secondary progressive multiple sclerosis. The
      secondary objectives are to evaluate safety, tolerability and efficacy at 2 years on the
      Multiple Sclerosis Functional Composite (MSFC), the percentage of patients with disability
      deterioration (EDSS) and the number of relapses. An intention-to-treat statistical analysis
      will be carried out.
    

Detailed description: 
      Background

      Preliminary not-controlled clinical studies of the efficacy of monthly intravenous
      cyclophosphamide administration in secondary progressive multiple sclerosis reported
      encouraging results, but no randomized controlled trial has been conducted so far. A slight
      efficacy of Methylprednisolone has been reported in this indication.

      Objectives

      The primary objective is to evaluate the efficacy of IV cyclophosphamide on the prevention of
      disability deterioration in patients with secondary progressive multiple sclerosis.

      The secondary objectives are to evaluate safety, tolerability and efficacy of IV
      cyclophosphamide on the Multiple Sclerosis Functional Composite (MSFC) and the number of
      relapses.

      Study design

      Randomized double-blind two-arm controlled trial.

      Intervention

      Experimental group : IV cyclophosphamide infusion administered every 4 weeks during 1 year
      and every 8 weeks during 1 year.

      Control group : IV methylprednisolone infusion administered every 4 weeks during 1 year and
      every 8 weeks during 1 year.

      Outcomes

      Primary outcome : delay to disability deterioration as assessed by the Expanded Disability
      Status Scale (EDSS: 0.5 or 1 point increase, depending on baseline score) evaluated every 4
      weeks for one year, then every 8 weeks for one year.

      Secondary outcomes : proportion of patients with disability deterioration (EDSS: 0.5 or 1
      point increase, depending on baseline score), Multiple Sclerosis Functional Composite (MSFC)
      and the Z scores of MSFC three components, number of MS relapses, proportion of patients with
      adverse events and delay of occurrence of adverse events, quality of life questionnaires.

        -  Quality of life questionnaires

        -  Disability self-assessment questionnaires Main time of assessment : 2 years.

      Sample size

      360 patients

      Statistical analysis

      Intention-to-treat analysis.
    

Intervention name(s): Cyclophosphamide (drug); Methylprednisolone (drug)
Intervention type(s): Drug; Drug
Intervention description(s): IV cyclophosphamide infusion administered every 4 weeks during 1 year and every 8 weeks during 1 year.; Control group : IV methylprednisolone infusion administered every 4 weeks during 1 year and every 8 weeks during 1 year.
Intervention MeSH terms: Methylprednisolone; Methylprednisolone Acetate; Methylprednisolone Hemisuccinate; Prednisolone; Prednisolone acetate; Cyclophosphamide; Prednisolone hemisuccinate; Prednisolone phosphate
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Multiple Sclerosis, Chronic Progressive; Cyclophosphamide; Methylprednisolone; Randomized Controlled Trials; Double-Blind Study