Duchenne muscular dystrophy (DMD) MedDRA version: 20.0 Level: PT Classification code 10013801 Term: Duchenne muscular dystrophy System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Interventions
Product Name: Vamorolone
Product Code: VBP15
Pharmaceutical Form: Oral suspension
INN or Proposed INN: VAMOROLONE
CAS Number: 13209-41-1
Current Sponsor code: VBP15
Concentration unit: % (W/W) percent
Sponsors
ReveraGen BioPharma, Inc.
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: 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: • Dystrophin immunofluorescence and/or immunoblot showing complete dystrophin deficiency, and clinical picture consistent with typical DMD, OR • 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 • 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; 3. Subject is =4 years and 13.0 kg and =39.9 kg at the Screening Visit; 5. Subject is able to walk independently without assistive devices; 6. Subject is able to complete the Time to Stand Test (TTSTAND) without assistance in =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 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 glucocorticoids or other oral immunosuppressive agents for indication other than DMD for no longer than 1 month cumulative, with last use at least 3 months prior to first dose of study medication, will be considered for eligibility on a case-by-case basis, unless discontinued for intolerence. 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 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 behavioural 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 has been administered a live attenuated vaccine within 14 days prior to the first dose of study medication; 15. 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; 16.Subject has a sibling who is currently enrolled in any vamorolone study or Expanded Access Program, or who intends to enroll in any vamorolone study or Expanded Access Program during the subject's participation in the VBP15-004 study; or 17. 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1. To compare the efficacy of vamorolone administered orally at daily doses of 6.0 mg/kg over a 24-week treatment period vs. placebo in ambulant boys ages 4 to <7 years with DMD; and 2. To evaluate the safety and tolerability of vamorolone administered orally at daily doses of 2.0 mg/kg and 6.0 mg/kg in ambulant boys ages 4 to <7 years with DMD.;Secondary Objective: 1. To compare the efficacy of vamorolone administered orally at daily doses of 2.0 mg/kg over a 24-week treatment period vs. placebo in ambulant boys ages 4 to <7 years with DMD; 2. & 3. To compare the safety (secondary obj. 2) and the safety (secondary obj. 3) of vamorolone administered orally at daily doses of 2.0 mg/kg and 6.0 mg/kg over a 24-week treatment period vs. daily prednisone 0.75 mg/kg in ambulant boys ages 4 to <7 years with DMD; 4. & 5. To compare the efficacy (secondary obj. 4.) and the safety (secondary obj. 5.) of vamorolone administered orally at daily doses of 2.0 mg/kg and 6.0 mg/kg over a 48-wk treatm. period in ambulant boys ages 4 to <7 years with DMD vs. respectively untreated DMD historical controls and prednisone-treated DMD historical controls; 6. To evaluate the population pharmacokinetics of vamorolone administered orally at daily doses of 2.0 mg/kg and 6.0 mg/kg in ambulant boys ages 4 to <7 years with DMD.;Primary end point(s): Primary Clinical Efficacy Endpoint 1. Time to Stand Test (TTSTAND) velocity (rise/second): Comparison of vamorolone 6.0 mg/kg/day dose level group versus the placebo group in change from baseline to the Week 24 assessment. For safety endpoints and pharmacodynamic endpoints see E.5.2;Timepoint(s) of evaluation of this end point: See E.5.1. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary Efficacy Endpoints 1. Change from baseline to Week 24 for the following comparisons: • TTSTAND velocity, vamorolone 2.0 mg/kg/day vs placebo • 6 Minute Walk Test (6MWT) meters walked, vamorolone 6.0 mg/kg/day vs. placebo • 6 Minute Walk Test (6MWT) meters walked, vamorolone 2.0 mg/kg/day vs. placebo • Time to Run/Walk (TTRW) 10 meters velocity, vamorolone 6.0 mg/kg/day vs. placebo • Time to Run/Walk (TTRW) 10 meters velocity, vamorolone 2.0 mg/kg/day vs. placebo • 6MWT meters walked, vamorolone 6.0 mg/kg/day vs. prednisone • 6MWT meters walked, vamorolone 2.0 mg/kg/day vs. prednisone 2. Change from baseline to each of the scheduled study assessment time points for each treatment group up to Week 48 for: • Time to Stand Test (TTSTAND) velocity (rise/second); • Time to Climb (4 Steps) Test (TTCLIMB) velocity (tasks/second); • Time to Run/Walk Test (TTRW) velocity (meters/second) to complete 10 meters of a 14 meter course; • Total distance traveled, in meters, in completing the Six-minute Walk Test (6MWT); • North Star Ambulatory Assessment (NSAA); • Hand-held myometry (elbow flexors and knee extensors); and • Range of motion in the ankles (ROM) Safety Endpoints 1. BMI z-score: Change from baseline to each of the scheduled on-treatment and post-treatment assessment time points; 2. Treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) by system organ class (SOC): Overall by treatment, by treatment and relationship, and by treatment and intensity (see Section 7.5); 3. Vital signs (sitting blood pressure, heart rate, respiratory rate, and body temperature): Change from baseline to each of the scheduled on-treatment and post-treatment assessment time points; 4. Body weight and height: Change from baseline to each of the scheduled on-treatment and post-treatment assessment time points; 5. Cushingoid features: Change from baseline to each of the scheduled on-treatment and post-treatment assessment time points (changes | — |
Countries
Australia, Belgium, Canada, Czechia, Czech Republic, Germany, Greece, Israel, Italy, Netherlands, Spain, Sweden, United Kingdom, United States
Contacts
Public ContactChrista van Kan
PSR Group B.V.
Outcome results
None listed