Delayed start analysis of efficacy outcomes in placebo to vamorolone crossover participants in VBP15-004


Clinical Trials

Poster Number: 89


Utkarsh Dang, PhD, Carleton University, Michela Guglieri, MD, John Walton Muscular Dystrophy Research Centre, Newcastle University, Newcastle upon Tyne, UK., Paula R. Clemens, MD, University of Pittsburgh School of Medicine, VA Pittsburgh Healthcare System, Pittsburgh, PA, USA, Seth Perlman, MD, Seattle Childrens, Edward Smith, MD, Duke University Hospital, Iain Horrocks, MD, Richard Finkel, MD, St. Jude Children’s Research Hospital, Memphis, TN, USA., Jean Mah, MD, University of Calgary, Nicolas Deconinck, MD, Centre de Référence Neuromusculaire and Paediatric Neurology Department, Hôpital Universitaire des E, Nathalie Goemans, MD, UZ Leuven, Jana Haberlova, MD, Volker Straub, MD, PhD, John Walton Muscular Dystrophy Research Centre and Newcastle Hospitals NHS Foundation Trust, UK, Amy Harper, MD, VCU Health, Perry Shieh, MD, University of California, Los Angeles, David Geffen School of Medicine, Liesbeth de Waele, MD, Diana Castro, MD, University of Texas Southwestern, Dallas, TX, USA., Michele Yang, MD, Monique Ryan, Dr, Murdoch Children's Research Institute, Craig McDonald, MD, UC Davis Health, Mar Tulinius, MD, Queen Silvia Children’s Hospital, Gothenburg, Sweden., Richard Webster, MD, The Children’s Hospital at Westmead, Sydney, Australia., Hugh McMillan, MD, Department of Pediatrics, Children’s Hospital of Eastern Ontario, Ottawa, ON, Canada, Nancy Kuntz, MD, Ann & Robert H. Lurie Children’s Hospital, Chicago, IL, USA., Giovanniu Baranello, MD, Dubowitz Neuromuscular Centre, UCL Great Ormond Street Institute of Child Health, London, UK., Stefan Spinty, MD, Alder Hey Children's Hospital, Liverpool, UK, Anne-Marie Childs, MD, Annie Sbrocchi, MD, Kathryn Selby, MD, Children's & Wowen's Health Centre of BC, Yoram Nevo, MD, Juan Vilchez, MD, Neuromuscular and Ataxias Research Group, Instituto de Investigación Sanitaria La Fe,Valencia, Spain, Andres Nascimento-Osorio, MD, Hospital Sant Joan de Déu, Unidad de Patología Neuromuscular, Universidad de Barcelona, Spain, Erik Niks, MD, Leiden University Medical Center, Imelda de Groot, MD, Radboud University Medical Center, Marina, Marina Katsalouli, Agia Sophia Children's Hospital, CINRG and VBP15-004 Investigators

Background: Vamorolone is a dissociative steroidal anti-inflammatory that seeks to retain efficacy and reduce safety concerns compared to corticosteroids via changes to structure/activity relationships with the glucocorticoid receptor. An open label study in Duchenne muscular dystrophy (DMD) suggested a favorable efficacy-safety profile, which was recently confirmed in a double blinded, prednisone- and place-controlled 48-week vamorolone trial with crossover (VBP15-004).
Objective: To present delayed start analysis of efficacy outcomes from VBP15-004.
Methods: Steroid-naïve boys with DMD (5.4±0.9 years; n=121) randomized to placebo for 24 weeks (Period 1) crossed-over to two vamorolone groups (2.0 or 6.0 mg/kg/day) for Period 2. An ancillary SAP pre-specified comparison of timed function test velocities (stand [TTSTANDV], climb [TTCLIMBV], and run/walk 10m [TTRWV], six-minute walk distance, and NSAA data from participants initially assigned to placebo (delayed-starters) vs. those assigned and retained on vamorolone throughout (early-starters). Change was modeled at weeks 12, 24, 40, and 48 using mixed models for repeated measures for early-starters (vamorolone 2.0 mg/kg/day [n=30]; vamorolone 6.0 mg/kg/day [n=28]) and delayed-starters (placebo->vamorolone 2.0 mg/kg/day [n=14]; placebo->vamorolone 6.0 mg/kg/day [n=14]).
Results: There was an improvement in multiple efficacy outcomes in delayed starters post-crossover to vamorolone after 24 weeks (e.g., TTSTANDV week 48 vs week 24; p < 0.05). Early-starters (vamorolone 6.0 mg/kg/day) had increased outcome means compared with delayed-starters (placebo->vamorolone 6.0 mg/kg/day) for all 5 outcomes at all timepoints with 1 exception (TTRWV at week 48). At 48 weeks, only the mean for TTCLIMBV was statistically significant between early- and delayed-starters (p<0.05). Other comparisons (e.g., vamorolone 2.0 mg/kg/day throughout vs. placebo->vamorolone 2.0 mg/kg/day or pooled dose groups) yielded similar findings for the most part.
Conclusions: A delayed start analysis of early-starters vs. delayed-starters showed that the initial disease-modifying effect of vamorolone with early initiation was maintained over follow-up period (although not always statistically significant). This global assessment of efficacy is supportive of the efficacy profile of vamorolone.