Duchenne Muscular Dystrophy MedDRA version: 28.0 Level: PT Classification code 10013801 Term: Duchenne muscular dystrophy System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Interventions
Trade Name: Agamree
Product Name: Agamree
Product Code: VBP15
Pharmaceutical Form: Oral suspension
INN or Proposed INN: Vamorolone
Current Sponsor code: VBP15
Concentration unit: % (W/W) percent weigh
Sponsors
Santhera Pharmaceuticals (Schweiz) AG
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, 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 clinical picture consistent with typical DMD; 3. Subject is male, 2 to =65 y
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 used mineralocorticoid receptor agents, such as spironolactone, eplerenone, canrenone (canrenoate potassium), prorenone (prorenoate potassium), or mexrenone (mexrenoate potassium) within 4 weeks prior to enrollment; 4. Subject has a history of primary hyperaldosteronism; 5. Subject has evidence of symptomatic cardiomyopathy [Note: Asymptomatic cardiac abnormality on investigation would not be exclusionary]; 6. If 2 to <4 years of age, 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 no longer than 1 month cumulative, with last use at least 3 months prior to enrollment, will be considered for eligibility on a case-by-case basis, unless discontinued for intolerance. Inhaled and/or topical glucocorticoids are permitted if last use is at least 4 weeks prior to enrollment or if administered at stable dose beginning at least 4 weeks prior to enrollment and anticipated to be used at the stable dose regimen for the duration of the study]; 7. Subject has an allergy or hypersensitivity to the study medication or to any of its constituents; 8. Subject has used idebenone within 4 weeks prior to enrollment; 9. Subject has severe behavioral or cognitive problems that preclude participation in the study, in the opinion of the Investigator; 10. 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; 11. Subject is taking (or has taken within 4 weeks prior to enrollment) herbal remedies and supplements which can impact muscle strength and function (e.g., Co-enzyme Q10, creatine, etc); 12. Subject is taking (or has taken within 3 months prior to enrollment) any medication indicated for DMD, including Exondys51, Exondys53, Exondys45, Viltepso and Translarna; 13. Subject has been administered a live attenuated vaccine within 14 days prior to the first dose of study medication; 14. Subject is currently taking any other investigational drug or has taken any other investigational drug within 3 months prior to enrollment; 15. Subject has previously been enrolled in the VBP15-006 study or any other vamorolone 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 negative anti-varicella IgG antibody test result.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the safety and tolerability of vamorolone administered orally at daily doses of 2.0 mg/kg and 6.0 mg/kg over a 3-month treatment period in boys ages 2 to <4 and 7 to <18 years with DMD.;Secondary Objective: 1. To evaluate the pharmacokinetics of vamorolone administered orally in boys ages 2 to <4 and 7 to <18 years with DMD; 2. To confirm the vamorolone exposure in boys ages 2 to <4 and 7 to18 years with DMD at 2.0 and 6.0 mg/kg and to adjust the doses if appropriate to achieve similar vamorolone AUCs across the entire pediatric age range.;Primary end point(s): Safety Endpoints (Endpoints Related to the Primary Objective) The following safety endpoints were evaluated for all age groups to address the primary objective. •Treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) •Change from Baseline to Week 12 in height, weight and body mass index (BMI) (absolute, percentile and Z-score) •Change from Baseline to each of the scheduled on-treatment and post-treatment assessment time points in vital signs •Cushingoid features (based on medical history and physical examination) Change from Baseline to each of the scheduled on-treatment and post-treatment assessment time points (changes from Baseline were to recorded as AEs) • Change from Baseline to each of the scheduled on-treatment and post-treatment assessment time points in clinical laboratory values -Hematology and clinical chemistry -Lipid profile (triglycerides, total cholesterol, low density lipoprotein [LDL], high density lipoprotein [HDL]) -Vitamin D level • Change from Baseline to each of the scheduled on-treatment and post-treatment assessment time points in 12-lead electrocardiogram (ECG) • Eye examination for detection of clinically significant abnormalities. Change from baseline to Week 12. ;Timepoint(s) of evaluation of this end point: All AEs and SAEs had to be recorded in the source documents and eCRF from the date of the subject’s written infor | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Pharmacokinetic Endpoints (Endpoints Related to a Secondary Objective) •Pre-dose and post-dose plasma concentration measurements of vamorolone at Day 1 and Week 2 •Other PK parameters (including AUCs and other relevant PK parameters) related to the other secondary endpoint ;Timepoint(s) of evaluation of this end point: Day 1 and Week 2 | — |
Countries
Canada
Contacts
Public ContactChief Medical Officer
Santhera Pharmaceuticals (Schweiz) AG
Outcome results
None listed