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: Vamarolone
Product Code: VBP15
Pharmaceutical Form: Oral suspension
INN or Proposed INN: vamorolone
CAS Number: 13209-41-1
Concentration unit: mg/kg milligram(s)/kilogram
Concentration
Sponsors
ReveraGen BioPharma, Inc.
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: 1. Participant’s parent or legal guardian has provided written informed consent/Health Insurance Portability and Accountability Act (HIPAA)authorization prior to any study-related procedures; 2. Participant has a confirmed (by Central Genetic Counselor) diagnosis of DMD as defined as: a) Dystrophin immunofluorescence and/or immunoblot showing complete dystrophin deficiency, and clinical picture consistent with typical DMD, OR b) 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 c) 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 typical clinical picture of DMD; Participant is = 4 years and =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Participant has current or history of major renal or hepatic impairment, diabetes mellitus or immunosuppression; 2. Participant has current or history of chronic systemic fungal or viral infections; 3. Participant has had an acute illness within 4 weeks prior to the first dose of study medication; 4. Participant 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. Participant has evidence of symptomatic cardiomyopathy [Note: Asymptomatic cardiac abnormality on investigation would not be exclusionary]; 6. Participant 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 no longer than 3 months 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. Inhaled and/or topical corticosteroids prescribed for an indication other than DMD are permitted but must be administered at stable dose for at least 3 months prior to study drug administration]; 7. Participant has used idebenone within 4 weeks prior to the first dose of study medication; 8. Participant has an allergy or hypersensitivity to the study medication or to any of its constituents; 9. Participant has severe behavioral or cognitive problems that preclude participation in the study, in the opinion of the Investigator; 10.Participant 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; 11.Participant is taking any other investigational drug currently or has taken any other investigational drug within 3 months prior to the start of study treatment; or 12.Participant has previously been enrolled in the study. Note: Any parameter/test may be repeated at the Investigator's discretion during Screening and/or Day 1 to determine sustainability and 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 if ineligible due to negative anti-varicella IgG antibody test result.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the safety and tolerability of multiple ascending oral doses of vamorolone in ambulant boys ages 4-< 7 years with DMD;Secondary Objective: 1. To investigate the single-dose and multiple-dose pharmacokinetics (PK) of oral vamorolone at multiple dose levels in ambulant boys ages 4-< 7 years with DMD; 2. To investigate the effects of single and multiple oral doses of vamorolone on serum pharmacodynamic (PD) biomarkers in ambulant boys ages 4-< 7 years with DMD; 3. To evaluate metabolites of vamorolone in Metabolites in Safety Testing (MIST) assessments following administration of multiple ascending oral doses.;Primary end point(s): Safety Endpoints 1. Treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs), by system organ class (SOC): overall by treatment, by treatment and relationship, by treatment and outcome, and by treatment and intensity (Common Terminology Criteria for Adverse Events [CTCAE] grade); 2. Vital sign [supine blood pressure (BP), heart rate, respiratory rate, oral temperature] values: change from Pretreatment to each of the scheduled on-treatment and post-treatment assessment time points; 3. Body weight: change from Pretreatment to each of the scheduled ontreatment and post-treatment assessment time points; 4. Clinical laboratory values: change from Pretreatment to each of the scheduled on-treatment and post-treatment assessment time points in: - Hematology and biochemistry - Lipid profile (triglycerides, total cholesterol, low density lipoprotein [LDL], high density lipoprotein [HDL]) - Urinalysis (urine protein and glucose); 5. Concentrations of serum metabolites of vamorolone; 6. 12-lead electrocardiogram (ECG) results: change from Pretreatment to Day 14 and Day 28; and 7. Physical examination findings of abnormality.;Timepoint(s) of evaluation of this end point: See E.5.1 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Pharmacodynamic Endpoints 1. Concentration of acute and chronic serum PD biomarkers (change from Pretreatment to on-treatment and post-treatment time points): osteocalcin, serum aminoterminal propeptide of type I collagen (P1NP), carboxy-terminal telopeptide (CTX), cortisol, ACTH, 17- hydroxyprogesterone, testosterone, corticosterone, and 11- deoxycortisol, insulin, and glucose and SomaScan and proteomics profiling. Exploratory Clinical Efficacy Endpoints All exploratory clinical efficacy measures are assessed as change from Pretreatment to each of the scheduled on-treatment and post-treatment assessment time points: 1. Quantitative Muscle Testing (QMT): unilateral elbow and knee muscle flexion and extension; 2. Time to Stand Test (TTSTAND) from a supine position; 3. Time to Climb 4 Steps Test (TTCLIMB); 4. Time to Run/Walk 10 meters Test (TTRW); 5. North Star Ambulatory Assessment (NSAA); and 6. Six-minute Walk Test (6MWT). Acceptability of vamorolone by a 5-point hedonic scale. Assessed ontreatment and post-treatment assessment time points Pharmacokinetic Endpoints Plasma PK parameters derived from serial blood samples collected 0.5 hour pre-dose and 1, 2, 4, 6, and 8 hours after the first and final doses of study drug on Day 1 and Day 14.;Timepoint(s) of evaluation of this end point: See E.5.2 | — |
Countries
Australia, Canada, Israel, Sweden, United Kingdom, United States
Contacts
Public ContactJesse Damsker
ReveraGen BioPharma Inc
Outcome results
None listed