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Clinical Program

The initial clinical development program for vamorolone focuses on Duchenne muscular dystrophy (DMD). DMD is of particular interest as it is the most common single gene disorder, affecting roughly 1:5,000 young boys worldwide.

An initial Phase 2 clinical trial in 48 DMD boys has been completed and published (NCT02760264) (Conklin et al. 2018). The trial was carried out by the Cooperative International Neuromuscular Research Group (CINRG), with trial management by TRiNDS LLC. Dr. Paula Clemens of University of Pittsburgh was the Study Chair.

This study showed (from Abstract of publication), “This 2-week, open-label Phase IIa multiple ascending dose study (0.25, 0.75, 2.0, and 6.0 mg/kg/day) enrolled 48 boys with Duchenne muscular dystrophy (4 to <7 years), with outcomes including clinical safety, pharmacokinetics and pharmacodynamic biomarkers. The study design included pharmacodynamic biomarkers in three contexts of use: 1. Secondary outcomes for pharmacodynamic safety (insulin resistance, adrenal suppression, bone turnover); 2. Exploratory outcomes for drug mechanism of action; 3. Exploratory outcomes for expanded pharmacodynamic safety. Vamorolone was safe and well-tolerated through the highest dose tested (6.0 mg/kg/day) and pharmacokinetics of vamorolone were similar to prednisolone. Using pharmacodynamic biomarkers, the study demonstrated improved safety of vamorolone versus glucocorticoids as shown by reduction of insulin resistance, beneficial changes in bone turnover (loss of increased bone resorption and decreased bone formation only at the highest dose level), and a reduction in adrenal suppression. Exploratory biomarkers of pharmacodynamic efficacy showed an anti-inflammatory mechanism of action and a beneficial effect on plasma membrane stability, as demonstrated by a dose-responsive decrease in serum creatine kinase activity. With an array of pre-selected biomarkers in multiple contexts of use, we demonstrate the development of the first dissociative steroid that preserves anti-inflammatory efficacy and decreases steroid-associated safety concerns.”

These 48 DMD boys were then enrolled into a 24 week extension study (VBP15-003; NCT02760277) to determine dose-response of clinical efficacy outcomes (timed function tests and other measures of strength, agility and endurance). These data are pending publication.

Forty six of the 48 patients continued on to a 2 year Long Term Extension study (VBP15-LTE; NCT03038399). This study had options for dose escalations, and all patients increased their vamorolone dose to either 2.0 or 6.0 mg/kg/day. Some patients have completed the LTE (a total of 2.5 years of vamorolone treatment; VBP15-002/003/LTE). An Expanded Access Program (EAP) has been established in the USA for those patients, families and physicians wishing to remain on vamorolone treatment, rather than transitioning to glucocorticoid (prednisone, deflazacort) standard of care.

A double-blind, placebo- and prednisone-controlled clinical trial is currently enrolling DMD patients (VBP15-004; NCT03439670). This study is recruiting 120 DMD boys, ages 4 to <7 years that have not previously been treated with glucocorticoids (prednisone, deflazacort). The study is enrolling at over 20 sites in Canada, USA, Europe, Israel and Australia. The study is managed by TRiNDS LLC, and study Co-Chairs are Drs. Michela Guglieri (Newcastle University) and Paula Clemens (University of Pittsburgh). Contact information for queries regarding enrollment into this trial can be found at the clinicaltrials.gov website for NCT03439670.