| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Duchenne Muscular Dystrophy (DMD) |
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| E.1.1.1 | Medical condition in easily understood language |
| Duchenne Muscular Dystrophy (DMD) |
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| E.1.1.2 | Therapeutic area | Diseases [C] - Musculoskeletal Diseases [C05] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10013801 |
| E.1.2 | Term | Duchenne muscular dystrophy |
| E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
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| E.1.3 | Condition being studied is a rare disease | Yes |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
Primary:
1. To evaluate the long-term safety and tolerability of vamorolone, administered orally at daily doses up to 6.0 mg/kg over a 24-month Treatment Period, in young boys with DMD who completed protocol VBP15-003; and
2. To compare the efficacy, as measured by the Time to Stand Test (TTSTAND), of vamorolone administered orally at daily doses up to 6.0 mg/kg over a 24-month Treatment Period vs. untreated DMD historical controls in young boys with DMD.
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| E.2.2 | Secondary objectives of the trial |
1. To investigate the effects of vamorolone, administered orally at daily doses up to 6.0 mg/kg over a 24-month Treatment Period on serum pharmacodynamic (PD) biomarkers of safety (insulin resistance, adrenal axis suppression, and bone turnover);
2. To investigate the effects of vamorolone, administered orally at daily doses up to 6.0 mg/kg over a 24-moth Treatment Period, on muscle strength, mobility and functional exercise capacity vs. untreated DMD historical controls as measured by Time to Run/Walk Test (TTRW), North Star Ambulatory Assessment (NSAA), Time to Climb Test (TTCLIMB), 6-minute Walk Test (6MWT), and Quantitative Muscle Testing (QMT) in young boys with DMD; and
3. To compare the safety, as assessed by bone age, spine fractures, BMI z-score, and height z-score, of vamorolone administered orally at daily doses up to 6.0 mg/kg over a 24-month Treatment Period vs. prednisone- and deflazocort-treated historical control boys with DMD. |
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| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Subject’s parent or legal guardian has provided written informed consent and HIPAA authorization (if applicable) prior to any VBP15-LTE longterm extension study-specific procedures;
2. Subject has previously completed study VBP15-003 up to and including the Week 24 Final assessments, prior to enrolling in the VBP15-LTE study at the conclusion of the VBP15-003 Week 24 Visit [Note: if entering the
dose-tapering period, subject is enrolling within 8 weeks after the VBP15-003 final visit following dose-tapering]; and
3. Subject and parent/guardian are willing and able to comply with scheduled visits, study drug administration plan, and study procedures.
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| E.4 | Principal exclusion criteria |
1. Subject had a serious or severe adverse event in study VBP15-003 that, in the opinion of the Investigator, was probably or definitely related to vamorolone use and precludes safe use of vamorolone for the subject in this long-term extension study;
2. Subject has current or history of major renal or hepatic impairment, diabetes mellitus or immunosuppression;
3. Subject has current or history of chronic systemic fungal or viral infections;
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 evidence of symptomatic cardiomyopathy. [Note: Asymptomatic cardiac abnormality on investigation would not be exclusionary];
6. 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 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 glucocorticoids
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. Subject has used idebenone within 4 weeks prior to the first dose of study
medication;
8. Subject has an allergy or hypersensitivity to the study medication or to any
of its constituents;
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 currently taking any investigational drug, or has taken any investigational drug other than vamorolone within 3 months prior to the start of study treatment.
Note: Subjects may be re-evaluated if ineligible due to a transient condition
which would prevent the subject from participating.
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| E.5 End points |
| E.5.1 | Primary end point(s) |
Safety Endpoints:
1. BMI z-score: Comparison with prednisone- and deflazacort-treated historical control groups for change from Baseline to Month 12 and Month 24;
2. BMI z-score: Change from Baseline to each of the scheduled on-treatment and post-treatment assessment time points;
3. Height z-score: Comparison with prednisone- and deflazacort-treated historical control groups for change from Baseline to Month 12 and Month 24;
4. 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
5. Vital signs [blood pressure, heart rate, respiratory rate, oral body temperature]: Change from Baseline to each of the scheduled on-treatment and post-treatment assessment time points;
6. Body weight: Change from Baseline to each of the scheduled on-treatment and post-treatment assessment time points;
7. Clinical laboratory values (hematology and biochemistry): Change from Baseline to each of the scheduled on-treatment and post-treatment assessment time points;
8. Lipid profile (triglycerides, total cholesterol, low density lipoprotein [LDL], high density lipoprotein [HDL]): Change from Baseline to each of the scheduled on-treatment and post-treatment assessment time points;
9. Urinalysis by dipstick and microscopic analysis: Change from Baseline to each of the scheduled on-treatment and post-treatment assessment time points;
10. 12-lead electrocardiogram (ECG): Change from Baseline to each of the scheduled on-treatment and post-treatment assessment time points;
11. Hand x-ray: bone age at Month 24;
12. Spine x-ray: Spine fractures at Month 24.
Data for the following additional safety outcomes will be listed only: Physical examination findings at Pretreatment, Month 12, and Month 24.
Clinical Efficacy Endpoint:
Time to Stand Test (TTSTAND) velocity (rise/second): Comparison with a historical natural history (untreated) control group for change from Baseline to Month 24. |
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| E.5.1.1 | Timepoint(s) of evaluation of this end point |
Clinical Efficacy Endpoint at Baseline, Month 24
Safety Endpoints: see E.5.1 |
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| E.5.2 | Secondary end point(s) |
Clinical Efficacy Endpoints:
1. Time to Stand Test (TTSTAND) velocity (rise/second): Comparison with a historical natural history (untreated) control group for change from Baseline to Month 12;
2. Time to Stand Test (TTSTAND): Change from Baseline to each of the scheduled on-treatment and post-treatment assessment time points;
3. Time to Climb (4 Steps) Test (TTCLIMB): Change from Baseline to each of the scheduled on-treatment and post-treatment assessment time points;
4. North Star Ambulatory Assessment (NSAA): Change in timed assessments and total score from Baseline to each of the scheduled on-treatment and post-treatment assessment time points;
5. Total distance traveled, in meters, in completing the Six-minute Walk Test (6MWT): Change from Baseline to each of the scheduled on-treatment and posttreatment assessment time points;
6. Time to Run/Walk Test (TTRW): Change from Baseline to each of the scheduled on-treatment and post-treatment assessment time points; and
7. Quantitative Muscle Testing (QMT): Change from Baseline to each of the scheduled on-treatment and post-treatment assessment time points.
Pharmacodynamic Endpoints:
Concentrations of serum PD biomarkers of adrenal suppression, insulin resistance, and bone turnover.
Exploratory Endpoints
1. Pediatric Outcomes Data Collection Instrument (PODCI): Change from baseline to each of the scheduled on-treatment and post-treatment assessment time points;
2. Levels of additional exploratory PD biomarkers; and
3. DNA testing for established genetic modifiers of DMD.
Endpoints for Subject Reported Outcomes
Safety endpoints based on subject reports of AEs are listed in the protocol (section 2.2.1.2). Additionally, subjects’ parents/legal guardians will be asked to complete the Pediatric Outcomes Data Collection Instrument. No other subject-reported outcomes are planned.
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| E.5.2.1 | Timepoint(s) of evaluation of this end point |
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| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | No |
| E.8.1.1 | Randomised | No |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | Yes |
| E.8.1.7.1 | Other trial design description |
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| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
| E.8.4 | The trial involves multiple sites in the Member State concerned | No |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 2 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Australia |
| Canada |
| Israel |
| United States |
| United Kingdom |
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| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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| Date of final analysis of the study data according to SAP (Statistical Analysis Plan) |
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| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | 2 |
| E.8.9.1 | In the Member State concerned days | 7 |
| E.8.9.2 | In all countries concerned by the trial years | 3 |
| E.8.9.2 | In all countries concerned by the trial months | 2 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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