Summary

for males ages 4-7 (full criteria)
at Davis, California and other locations
study started
estimated completion
Craig McDonald, MD

Description

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.

Official Title

A Phase IIb Randomized, Double-blind, Parallel Group, Placebo- and Active-controlled Study With Double-Blind Extension to Assess the Efficacy and Safety of Vamorolone in Ambulant Boys With Duchenne Muscular Dystrophy (DMD)

Details

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.

A total of approximately 120 subjects will be randomized (2:2:1:1:1:1) to treatment.

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.

At the end of the Treatment Period #2, subjects will be given the option of enrolling into a long-term extension study (VBP15-005) or to transition to standard of care treatment for DMD (may include glucocorticoids). Subjects completing VBP15-004 and enrolling directly into VBP15 005 will not need to taper their vamorolone dose prior to enrollment into VBP15 005. 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.

Keywords

Duchenne Muscular Dystrophy Vamorolone Muscular Dystrophies Muscular Dystrophy, Duchenne Prednisone

Eligibility

You can join if…

Open to males ages 4-7

  1. Subject's parent(s) or legal guardian(s) has (have) provided written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization, where applicable, prior to any study-related procedures; participants will be asked to give written or verbal assent according to local requirements
  2. Subject has a centrally confirmed (by TRiNDS central genetic counselor[s]) diagnosis of DMD as defined as:
  3. Dystrophin immunofluorescence and/or immunoblot showing complete dystrophin deficiency, and clinical picture consistent with typical DMD, OR
  4. Identifiable mutation within the DMD gene (deletion/duplication of one or more exons), where reading frame can be predicted as 'out-of-frame,' and clinical picture consistent with typical DMD, OR
  5. Complete dystrophin gene sequencing showing an alteration (point mutation, duplication, other) that is expected to preclude production of the dystrophin protein (i.e., nonsense mutation, deletion/duplication leading to a downstream stop codon), with a clinical picture consistent with typical DMD;
  6. Subject is ≥ 4 years and <7 years of age at time of enrollment in the study;
  7. Subject weighs >13.0 kg and ≤ 39.9 kg at the Screening Visit;
  8. Subject is able to walk independently without assistive devices;
  9. Subject is able to complete the Time to Stand Test (TTSTAND) without assistance in <10 seconds, as assessed at the Screening Visit;
  10. Clinical laboratory test results are within the normal range at the Screening Visit, or if abnormal, are not clinically significant, in the opinion of the Investigator. [Note: Serum gamma glutamyl transferase (GGT), creatinine, and total bilirubin all must be ≤ upper limit of the normal range at the Screening Visit];
  11. Subject has evidence of chicken pox immunity as determined by presence of IgG antibodies to varicella, as documented by a positive test result from the local laboratory at the Screening Visit;
  12. Subject is able to swallow tablets, as confirmed by successful test swallowing of placebo tablets during the Screening Period; and
  13. . Subject and parent(s)/guardian(s) are willing and able to comply with scheduled visits, study drug administration plan, and study procedures.

You CAN'T join if...

  1. Subject has current or history of major renal or hepatic impairment, diabetes mellitus or immunosuppression;
  2. Subject has current or history of chronic systemic fungal or viral infections;
  3. Subject has had an acute illness within 4 weeks prior to the first dose of study medication;
  4. Subject has used mineralocorticoid receptor agents, such as spironolactone, eplerenone, canrenone (canrenoate potassium), prorenone (prorenoate potassium), mexrenone (mexrenoate potassium) within 4 weeks prior to the first dose of study medication;
  5. Subject has a history of primary hyperaldosteronism;
  6. Subject has evidence of symptomatic cardiomyopathy [Note: Asymptomatic cardiac abnormality on investigation would not be exclusionary];
  7. Subject is currently being treated or has received previous treatment with oral glucocorticoids or other immunosuppressive agents [Notes: Past transient use of oral or inhaled glucocorticoids or other oral immunosuppressive agents for indication other than DMD for no longer than 3 months cumulative, with last use at least 3 months (or last use at least one month prior for inhaled glucocorticoids) prior to first dose of study medication, will be considered for eligibility on a case-by-case basis. Inhaled and/or topical glucocorticoids prescribed for an indication other than DMD are permitted if last use is at least 4 weeks prior to first dose of study medication or are administered at stable dose beginning at least 4 weeks prior to first dose of study medication, and are anticipated to be used at the stable dose regimen for the duration of the study];
  8. Subject has an allergy or hypersensitivity to the study medication or to any of its constituents;
  9. Subject has used idebenone within 4 weeks prior to the first dose of study medication;
  10. . Subject has severe behavioral or cognitive problems that preclude participation in the study, in the opinion of the Investigator;
  11. . Subject has previous or ongoing medical condition, medical history, physical findings or laboratory abnormalities that could affect safety, make it unlikely that treatment and follow-up will be correctly completed or impair the assessment of study results, in the opinion of the Investigator;
  12. . Subject is taking (or has taken within 4 weeks prior to the first dose of study medication) herbal remedies and supplements which can impact muscle strength and function (e.g., Co-enzyme Q10, creatine, proglandine, etc);
  13. . Subject is taking (or has taken within 3 months prior to the first dose of study medication) any medication indicated for DMD, including Exondys51 and Translarna;
  14. . Subject is currently taking any other investigational drug or has taken any other investigational drug within 3 months prior to the first dose of study medication; or
  15. . Subject has previously been enrolled in the study.

Note: Any parameter/test may be repeated at the Investigator's discretion during Screening to determine reproducibility. In addition, subjects may be rescreened if ineligible due to a transient condition which would prevent the subject from participating, such as an upper respiratory tract infection or injury, or if ineligible due to negative anti-varicella IgG antibody test result.

Locations

  • University of California Davis accepting new patients
    Davis California 95616 United States
  • University of California Los Angeles accepting new patients
    Los Angeles California 90095 United States

Lead Scientist

  • Craig McDonald, MD
    Professor, Physical Medicine and Rehabilitation. Authored (or co-authored) 125 research publications

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
ReveraGen BioPharma, Inc.
Links
Sign up for this study
ID
NCT03439670
Phase
Phase 2
Study Type
Interventional
Last Updated