Journal of neurology · 2026
Results of a phase II open-label, multiple-dose study of vamorolone (VBP15-006) in 7- to < 18-year-old boys with duchenne muscular dystrophy.
СтатьяКлиническое исследование II фазыНазвание и аннотация: Перевод в очереди
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Lochmüller Hanns, Gonorazky Hernan, Nigro Elisa, Mah Jean K, Alemán Alberto, Yaworski Amanda, Oskoui Maryam, Sbrocchi Anne Marie, Selby Kathryn, de Vera Ana, McAdam Laura, Gresko Ekaterina, Linden Aki, Dutreix Catherine, Hoffman Eric P
Аннотация
BACKGROUND: Vamorolone is a dissociative glucocorticoid receptor agonist for treating Duchenne muscular dystrophy (DMD). The VBP15-006 study assessed vamorolone safety, tolerability, and pharmacokinetics in 2- to < 4 and 7- to < 18-year-old boys with DMD. Results for 7- to < 18-year-old boys, either corticosteroid (CS)-untreated or switching from prior CS treatment, are reported here. Exploratory objectives included efficacy and pharmacodynamic biomarkers related to safety.
METHODS: In this phase II, open-label, multiple-dose study, participants received 2 or 6 mg/kg/day vamorolone for 12 weeks, followed by treatment in an expanded access protocol (EAP Canada).
RESULTS: 34 participants (12 CS-untreated, 22 CS-treated) aged 7- to < 18 years were enrolled. Most treatment-emergent adverse events were mild. All 34 participants completed VBP15-006 and entered EAP Canada. During EAP Canada, CS-untreated participants maintained stable linear growth, while CS-treated participants exhibited catch-up growth consistent with serum bone biomarkers (median total vamorolone exposure 1.3 and 1.7 years, respectively). Some weight gain occurred, especially in CS-untreated participants receiving 6 mg/kg/day. Dose-dependent adrenal suppression occurred in CS-untreated and CS-treated participants; 2 individuals who switched from deflazacort to vamorolone 2 mg/kg/day had generalized weakness consistent with adrenal insufficiency. Vamorolone showed dose-dependent pharmacokinetics, rapid clearance, and no accumulation. There were no relevant efficacy changes in CS-treated and CS-untreated groups at either dose.
CONCLUSIONS: Vamorolone demonstrated a consistent safety profile in 7- to < 18-year-old boys with DMD. Switching to 6 mg/kg/day vamorolone appeared to mitigate adrenal insufficiency risk. There was no negative effect on growth, and catch-up growth occurred in previously CS-treated individuals switching to vamorolone.
TRIAL REGISTRATION: ClinicalTrials.gov: NCT05185622, NCT03863119. First submitted 09-11-2021.
METHODS: In this phase II, open-label, multiple-dose study, participants received 2 or 6 mg/kg/day vamorolone for 12 weeks, followed by treatment in an expanded access protocol (EAP Canada).
RESULTS: 34 participants (12 CS-untreated, 22 CS-treated) aged 7- to < 18 years were enrolled. Most treatment-emergent adverse events were mild. All 34 participants completed VBP15-006 and entered EAP Canada. During EAP Canada, CS-untreated participants maintained stable linear growth, while CS-treated participants exhibited catch-up growth consistent with serum bone biomarkers (median total vamorolone exposure 1.3 and 1.7 years, respectively). Some weight gain occurred, especially in CS-untreated participants receiving 6 mg/kg/day. Dose-dependent adrenal suppression occurred in CS-untreated and CS-treated participants; 2 individuals who switched from deflazacort to vamorolone 2 mg/kg/day had generalized weakness consistent with adrenal insufficiency. Vamorolone showed dose-dependent pharmacokinetics, rapid clearance, and no accumulation. There were no relevant efficacy changes in CS-treated and CS-untreated groups at either dose.
CONCLUSIONS: Vamorolone demonstrated a consistent safety profile in 7- to < 18-year-old boys with DMD. Switching to 6 mg/kg/day vamorolone appeared to mitigate adrenal insufficiency risk. There was no negative effect on growth, and catch-up growth occurred in previously CS-treated individuals switching to vamorolone.
TRIAL REGISTRATION: ClinicalTrials.gov: NCT05185622, NCT03863119. First submitted 09-11-2021.