Results of VBP15-006: a Phase 2 open-label, multiple dose study of vamorolone in boys with DMD aged 2–<4 and 7–<18 years.

Topic:

Clinical Trials

Poster Number: V407

Author(s):

Jean K Mah, MD, Alberta Children’s Hospital Research Institute, University of Calgary, Calgary, Alberta, Canada, Hernan D. Gonorazky, MD, CSCN, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada, Hanns Lochmuller, MD, Children’s Hospital of Eastern Ontario Research Institute, Alberto Aleman, Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, Canada, Amanda Yaworski, Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, Canada, Maryam Oskoui, MD, Department of Pediatrics and Neurology & Neurosurgery, McGill University, Montreal, Quebec, Canada, Anne Marie Sbrocchi, MD, FRCPC, Department of Pediatrics and Neurology & Neurosurgery, McGill University, Montreal, Quebec, Canada, Ana de Vera, MD, Santhera Pharmaceuticals (Switzerland) Ltd, Pratteln, Switzerland, Catherine Dutreix Dutreix, Santhera Pharmaceuticals (Switzerland) Ltd, Pratteln, Switzerland, Ekaterina Gresko, Santhera Pharmaceuticals (Switzerland) Ltd, Pratteln, Switzerland, Aki Linden, Santhera Pharmaceuticals (Switzerland) Ltd, Pratteln, Switzerland, Anders Berglund, Santhera Pharmaceuticals (Switzerland) Ltd, Pratteln, Switzerland, Pascal Charef, Santhera Pharmaceuticals (Switzerland) Ltd, Pratteln, Switzerland, Eric Hoffman, PhD, Reveragen BioPharma, Rockville, Maryland, United States of America, Jesse Damsker, PhD, Reveragen BioPharma, Rockville, Maryland, United States of America, Kathryn Selby, MD, The University of British Columbia, Children's and Women's Health Centre, Vancouver, Canada

Background: Vamorolone, a dissociative corticosteroid, is approved for treatment of boys with Duchenne muscular dystrophy (DMD) in the USA, Europe and UK.
Objective: VBP15-006 (NCT05185622) was a Phase 2 open-label, multiple dose study in Canada, designed to confirm the safe and tolerable dose(s) of Vamorolone for 2–<4 years and 7–<18 years boys with DMD, based upon safety and PK data over 12 weeks treatment. Methods: Participants (N=54) were allocated to Vamorolone 2 or 6 mg/kg/day dose groups by age at study baseline. Participants aged 2–<4 years were corticosteroid (CS)-naïve and treated with Vamorolone 2 mg/kg/day (n=10; median age 3.3 years) or 6 mg/kg/day (n=10; median age 3.5 years). Participants aged 7–<18 years were either CS-untreated (Vamorolone 2 mg/kg/day [n=6; median age 8.0 years] or 6 mg/kg/day [n=6; median age 8.0 years]), or CS-treated (Vamorolone 2 mg/kg/day [n=6; median age 10.2 years] or 6 mg/kg/day [n=16; median age 13.0 years]). Results: All subjects completed the study. Baseline characteristics were as expected for the CS-naïve and previously untreated subjects. Median past CS exposure in the 7–<18 years CS-treated Vamorolone 2 and 6 mg/kg/day groups was 54.1 and 93.1 months, respectively. Baseline co-morbidities in CS-treated subjects included fractures, cataracts, psychiatric and endocrine disorders. At baseline, severe growth delay (median height percentile of 1.6 (0.2;16.8)), was reported for 7–<18 years CS-treated Vamorolone 6 mg/kg/day group. Vamorolone showed dose-dependent pharmacokinetics over dose range of 2 to 6 mg/kg, with maximum concentration reached within 2-4 hours, and a half-life of 2 hours. Exposures were consistent with moderate variability at both doses after single and multiple dosing across all age groups. Dose-dependent increases in adverse events were seen across all age groups; none led to study discontinuation or death. Conclusions: These results support potential use of Vamorolone across a broad age range in children with DMD.