A Study to Assess the Efficacy and Safety of Vamorolone in Boys With Duchenne Muscular Dystrophy (DMD)
Condition: Duchenne Muscular Dystrophy
MeSH terms: Muscular Dystrophies; Muscular Dystrophy, Duchenne
Study type: Interventional
Phase: Phase 2

Summary: 
      Brief Summary: This Phase IIb study is a randomized, double-blind, parallel group, placebo
      and active-controlled study to evaluate the efficacy, safety, PD, and population PK of
      vamorolone administered orally at daily doses of 2.0 mg/kg and 6.0 mg/kg versus prednisone
      0.75 mg/kg/day and placebo over a Treatment Period of 24 weeks, and to evaluate persistence
      of effect over a Treatment Period of 48 weeks in ambulant boys ages 4 to <7 years with DMD.
    

Detailed description: 
      This Phase IIb study is a randomized, double-blind, parallel group, placebo and
      active-controlled study to evaluate the efficacy, safety, PD, and population PK of vamorolone
      administered orally at daily doses of 2.0 mg/kg and 6.0 mg/kg versus prednisone 0.75
      mg/kg/day and placebo over a Treatment Period of 24 weeks, and to evaluate persistence of
      effect over a Treatment Period of 48 weeks in ambulant boys ages 4 to <7 years with DMD.

      The study is comprised of a 5-week Pretreatment Screening Period, a 1-day Pretreatment
      Baseline Period, a 24-week Treatment Period #1 (Weeks 1-24), a 4-week Transition Period
      (Weeks 25-28), a 20-week Treatment Period #2 (Weeks 28 + 1 day to 48), and a 4-week
      Dose-tapering Period (Weeks 49-52).

      Subjects will be randomized to one of six treatment groups in a 2:2:1:1:1:1 ratio, where the
      two prednisone groups in Treatment Period #1 (Groups 3 and 4) will be combined and the two
      placebo groups in Treatment Period #1 (Groups 5 and 6) will be combined, effectively
      resulting in a 1:1:1:1 randomization (vamorolone 2.0 mg/kg/day : vamorolone 6.0 mg/kg/day :
      prednisone 0.75 mg/kg/day : placebo) for Treatment Period #1.

      Subjects will be stratified based on age at study entry (<6 vs. ≥ 6 years). During the 4-week
      Transition Period between Treatment Period #1 and Treatment Period #2, all subjects will
      continue on the same oral suspension (vamorolone 2.0 mg/kg or 6.0 mg/kg, or matching placebo)
      they received during Treatment Period #1 and all subjects will have their tablet dose tapered
      to zero. Thus, subjects randomized to receive vamorolone during Treatment Period #1 (Groups 1
      and 2) will continue to receive vamorolone at the same dose, while subjects randomized to
      receive prednisone will have their dose tapered to zero, and subjects randomized to placebo
      will continue to receive placebo.

      The prednisone group will be used as an active control comparison for safety and efficacy
      endpoints as requested by the European Medicines Agency (EMA). The placebo group will be used
      as comparator for efficacy endpoints (superiority model) as requested by the EMA and Food and
      Drug Administration (FDA) protocol advisory board. Although glucocorticoids are part of the
      care recommendations for DMD, their adverse effect profile has limited their use. The age at
      which glucocorticoids should be started in DMD boys is uncertain, ranging from 4 to 7 years,
      based on a balance between benefits and side effects. In view of the age inclusion criteria
      and duration of the placebo-controlled study period (6 months), the use of a placebo group
      has been considered acceptable as in clinical practice it will not cause a real delay in
      prescription of an accepted treatment for this condition. Any exposure of placebo longer than
      6 months was considered unethical.

      At the end of the Treatment Period #2, subjects may be given access to vamorolone through an
      additional study or general access program, or given the option to transition to standard of
      care treatment for DMD (may include glucocorticoids). Subjects completing VBP15-004 and
      enrolling directly into an additional vamorolone study or general access program to receive
      vamorolone will not need to taper their vamorolone dose prior to enrollment. All other
      subjects will begin a 4-week double-blind Dose-tapering Period during which the dose of study
      medication will be progressively reduced and discontinued.
    

Intervention name(s): Vamorolone; Prednisone; Placebo; Vamorolone; Prednisone; Placebo; Vamorolone; Vamorolone
Intervention type(s): Drug; Drug; Other; Drug; Drug; Other; Drug; Drug
Intervention description(s): Oral administration of 2.0 mg/kg/day for the duration of the study.; Oral administration of 0.75 mg/kg/day for 24 weeks.; Oral administration of placebo daily for 24 weeks.; Oral administration of 6.0 mg/kg/day for the duration of the study.; Oral administration of 0.75 mg/kg/day for 24 weeks.; Oral administration of placebo daily for 24 weeks.; Oral administration of 2.0 mg/kg/day for 20 weeks.; Oral administration of 6.0 mg/kg/day for 20 weeks.
Other intervention name(s): VBP15; VBP15; VBP15; VBP15
Intervention MeSH terms: Prednisone
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Duchenne Muscular Dystrophy; Vamorolone