Neurology Clinical Trial Database
Vamorolone for DMD
Vamorolone Safety, Pharmacokinetics, and Exploratory Efficacy in Duchenne Muscular Dystrophy: A Phase II, Nonrandomized, Multiple-Dose Study in 2-<4-Year-Old Boys
Bottom Line
In 20 corticosteroid-naive boys aged 2-<4 years with DMD, 12 weeks of vamorolone (2 or 6 mg/kg/d) was well tolerated with no serious adverse events and stable growth, dose-dependent adrenal suppression (asymptomatic), dose-dependent pharmacokinetics, and dose-dependent gross motor improvement favoring 6 mg/kg/d.
Major Points
- Phase II, open-label, nonrandomized, multiple-dose study at 5 Canadian sites; 10 patients each received vamorolone 2 mg/kg/d then 6 mg/kg/d sequentially for 12 weeks, followed by an Expanded Access Protocol (EAP) with data snapshot at ~2 years of exposure.
- Safety: 70% (2 mg/kg/d) and 90% (6 mg/kg/d) had at least one TEAE; no deaths, no serious TEAEs, no discontinuations; most TEAEs were mild GI events (80% at 6 mg/kg/d) and infections (50% at 2 mg/kg/d, mainly nasopharyngitis).
- Adrenal suppression (morning cortisol ≤65 nmol/L) at week 12 occurred in 20% (2/10) at 2 mg/kg/d and 40% (4/10) at 6 mg/kg/d; all asymptomatic; 3 patients required hydrocortisone stress dosing during study.
- Growth: stable height, weight, and BMI z-scores over 12 weeks; ~2 years of EAP follow-up showed median CBL height-score 0.066, BMI-score 0.234; 8/19 patients had BMI-score change >0.5 suggesting excessive weight gain.
- Pharmacokinetics: dose-dependent Cmax and AUC with rapid absorption (Tmax ~2 h); no accumulation between day 1 and week 2; profile consistent with prior data in 4-<7 year-olds.
- Exploratory efficacy: median Bayley-III gross motor scaled score change from baseline to week 12 was 0.0 (2 mg/kg/d) vs 2.5 (6 mg/kg/d), suggesting dose-dependent motor benefit favoring 6 mg/kg/d.
- Bone turnover biomarkers (osteocalcin, CTX1, P1NP) and glucose metabolism markers (fasting glucose, HbA1c, insulin) remained stable at both doses.
- Class IV evidence given the small (n=20), open-label, nonrandomized design; no formal hypothesis testing was planned.
Design
Study Type: Phase II, open-label, nonrandomized, multiple-dose clinical trial
Randomization:
Blinding: Open-label
Enrollment Period: March 21, 2022 - June 17, 2024 (last patient completed VBP15-006)
Follow-up Duration: 12 weeks (primary); ~2 years median in EAP Canada extension
Centers: 5
Countries: Canada
Sample Size: 20
Analysis: Descriptive; no formal hypothesis testing; 20 participants (10 per dose group) considered sufficient for TEAE rate estimation and PK characterization
Inclusion Criteria
- Male sex
- Age 2-<4 years
- Duchenne muscular dystrophy confirmed by genetic testing and/or dystrophin deficiency on muscle biopsy
- Evidence of varicella zoster virus immunity
- Corticosteroid-naive (no prior oral glucocorticoid or oral immunosuppressive therapy)
- Ambulatory at baseline
- Written informed consent from parent/legal guardian
Exclusion Criteria
- Prior or current oral glucocorticoid or immunosuppressive therapy
- Immunosuppression
- Diabetes mellitus
- Major renal impairment
- Major hepatic impairment
Arms
| Field | Vamorolone 2 mg/kg/d | Vamorolone 6 mg/kg/d |
|---|---|---|
| Intervention | Oral vamorolone suspension (4% w/v in flavored syrup) 2 mg/kg/d once daily at breakfast | Oral vamorolone suspension (4% w/v in flavored syrup) 6 mg/kg/d once daily at breakfast |
| Duration | 12 weeks + EAP extension | 12 weeks + EAP extension |
Outcomes
| Outcome | Type | Control | Intervention | HR / OR / RR | P-value |
|---|---|---|---|---|---|
| Safety and tolerability: TEAEs, SAEs, and change from baseline to week 12 in height, weight, and BMI | Primary | 2 mg/kg/d: 70% (7/10) had ≥1 TEAE (18 events); 0 SAEs; median CBL height-score -0.04, weight-score -0.01, BMI-score 0.12 | 6 mg/kg/d: 90% (9/10) had ≥1 TEAE (39 events); 0 SAEs; median CBL height-score 0.09, weight-score 0.13, BMI-score -0.13 | Not applicable (descriptive) | |
| PK: Cmax day 1 (geometric mean) | Secondary | 2 mg/kg/d: 246.8 ng/mL | 6 mg/kg/d: 781.7 ng/mL | Descriptive | |
| PK: Cmax week 2 (geometric mean) | Secondary | 2 mg/kg/d: 349.3 ng/mL | 6 mg/kg/d: 719.5 ng/mL | Descriptive | |
| Tmax | Secondary | ~2 h | ~2 h | Descriptive | |
| Adrenal suppression (cortisol ≤65 nmol/L) at week 12 | Secondary | 2 mg/kg/d: 20% (2/10) | 6 mg/kg/d: 40% (4/10) | Descriptive | |
| Bayley-III GMSS median change from baseline to week 12 (exploratory) | Secondary | 2 mg/kg/d: 0.0 (Q1;Q3: 0.0; 1.0) | 6 mg/kg/d: 2.5 (Q1;Q3: 2.0; 4.0) | Descriptive | |
| Bone turnover (CTX1) median CBL, ng/L | Secondary | 2 mg/kg/d: -35.5 | 6 mg/kg/d: 228.0 | Descriptive | |
| Fasting glucose median CBL, mmol/L | Secondary | 2 mg/kg/d: -0.165 | 6 mg/kg/d: -0.385 | Descriptive | |
| HbA1c median CBL | Secondary | 2 mg/kg/d: 0.001 | 6 mg/kg/d: 0.000 | Descriptive | |
| Ease of administration (cooperatively without opposition) | Secondary | 2 mg/kg/d: 9/10 | 6 mg/kg/d: 9/10 | Descriptive | |
| Any TEAE | Adverse | 70% (2 mg) vs 90% (6 mg) | |||
| Any drug-related TEAE | Adverse | 10% (2 mg) vs 70% (6 mg) | |||
| Serious TEAE | Adverse | 0% vs 0% | |||
| Discontinuations due to TEAE | Adverse | 0% vs 0% | |||
| Deaths | Adverse | 0 vs 0 | |||
| GI disorders (SOC) | Adverse | 10% (2 mg) vs 80% (6 mg) | |||
| Diarrhea | Adverse | 0% vs 30% | |||
| Abdominal pain upper | Adverse | 0% vs 20% | |||
| Toothache | Adverse | 0% vs 20% | |||
| Endocrine disorders (adrenal suppression) | Adverse | 0% vs 50% | |||
| Infections and infestations | Adverse | 50% (2 mg) vs 30% (6 mg) | |||
| Nasopharyngitis | Adverse | 40% vs 30% | |||
| Musculoskeletal disorders | Adverse | 0% vs 40% | |||
| Pain in extremity | Adverse | 0% vs 20% | |||
| Pyrexia | Adverse | 10% vs 10% | |||
| Psychiatric disorders (irritability, aggression, lip biting, mood swings) | Adverse | 0% vs 20% (all mild, no treatment required) | |||
Subgroup Analysis
Post hoc Bayley-III GMSS by age: patients ≤3.5 y had median CBL 0.5 (2 mg/kg/d, n=4) vs 2.0 (6 mg/kg/d, n=2); patients >3.5 y had 0.0 (n=5) vs 2.5 (n=8), showing dose-dependent motor improvement across age subgroups.
Criticisms
- Small sample size (n=20; 10 per arm) limits precision of safety and efficacy estimates
- Open-label, nonrandomized, single-country (Canada) design provides only Class IV evidence
- Sequential (not concurrent) allocation to dose groups introduces potential temporal confounding
- No placebo or classic corticosteroid comparator; efficacy interpretation relies on historical controls
- Short 12-week primary treatment period is insufficient to fully evaluate long-term growth, bone health, or motor function; EAP follow-up used routine-care data quality only
- Bayley-III is validated only up to 3.5 years, but was used in all participants; efficacy signal driven partly by patients above the validated age range
- PK terminal half-life and AUC-infinity could not be calculated due to sparse sampling; high interpatient variability
- Industry-sponsored study (Santhera/ReveraGen); several coauthors are company employees
- Age distribution skewed toward the upper end of the 2-<4 y range (median 3.4 y), limiting generalizability to the youngest patients
- Fasting insulin data unavailable for 2 mg/kg/d group due to central-laboratory sample-handling oversight
Funding
Santhera Pharmaceuticals (sponsor); vamorolone codeveloped with ReveraGen BioPharma
Based on: Vamorolone for DMD (Neurology, 2026)
Authors: Mah JK, Gonorazky HD, Nigro E, et al.
Citation: Neurology 2026;106(11):e218066
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