Clinical Trials

Vamorolone has been studied in a series of clinical trials in both adult healthy volunteers (Phase I), and in DMD boys (Phase 2).

The Phase 1 studies were carried out in 86 adult volunteers in 2015. The volunteers received either a single dose of vamorolone (0.1 – 20.0 mg/kg) or 14 doses (2 weeks daily dosing; 1.0 – 20.0 mg/kg/day). These studies have been published and showed that vamorolone was safe to the highest doses tested (20.0 mg/kg/day; or about 10-15 times higher than typical corticosteroid doses in DMD). While clinical benefit of vamorolone could not be studied in healthy volunteers, there was evidence of lessened side effects based on blood biomarker studies.

Clinical trials in DMD boys were initiated in 2016 with a Phase 2a study (VBP15-002) in 48 boys (ages 4 to <7 years old). This study was carried out by the Cooperative International Neuromuscular Research Group (CINRG) – a clinical trial network that has also carried out the largest natural history studies of DMD. The Phase 2a study was a 4 week study, where vamorolone was given at one of 4 doses for 2 weeks (0.25, 0.75, 2.0 and 6.0 mg/kg/day), followed by a 2 week washout (no drug). The primary findings were that vamorolone seemed safe (consistent with adult volunteer studies), and that the pharmacokinetics were similar to traditional corticosteroids (good bioavailability with short half-life). The pharmacokinetics of the adult volunteers and DMD boys were also analyzed together to calculate population pharmacokinetics (PopPK), and this has also been published.

As the DMD boys completed the 4-week VBP15-002 study, they were enrolled into the VBP15-003 study (6-month extension), where they were maintained at the same dose as in the 4-week study (0.25 – 6.0 mg/mg/day). The 6-month treatment showed that higher doses of vamorolone (2.0 and 6.0 mg/kg/day) resulted in significant improvements in muscle function in DMD boys, and these studies were also published. The study of blood biomarkers also suggested that side effects of vamorolone were reduced compared to corticosteroids.

The large majority (46 of 48) of the boys enrolled in the VBP15-002/003 studies, their families and their physicians expressed a desire to continue treatment with vamorolone after they had completed these initial clinical trials. A 2-year long-term extension study was then implemented (VBP15-LTE), and this study permitted the physician, in discussion with patient families, to alter the dose of vamorolone. All the patients on the two lower doses (0.25 and 0.75 mg/kg/day) were escalated to the two higher doses (2.0 and 6.0 mg/kg/day) with most choosing the highest dose (6.0 mg/kg/day).

All patients in the long-term extension have completed 18-months of vamorolone treatment (mid-point of LTE). As reported at the 2019 World Muscle Society conference, patients treated for 18-months appear to show continued improvement, while lacking the corticosteroid side effect of stunting of growth seen with deflazacort and prednisone.

The LTE study is ongoing, although some patients have now completed the 2.5 years of vamorolone treatment (VBP15-002, VBP15-003, VBP15-LTE). The majority of patients, families and their physicians have expressed desire to continue treatment with vamorolone rather than transition to corticosteroid standard of care. An Expanded Access Protocol has been initiated in the USA for these patients completing the LTE, and similar mechanisms are being implemented in other countries to enable continued access to vamorolone after exit from clinical trials.

In 2018 a pivotal (Phase 3-type) clinical trial initiated enrollment (VBP15-004). This trial is recruiting DMD boys ages 4 to <7 years. Boys are randomized into one of four dose groups for 6 months (2.0 or 6.0 mg/kg/day vamorolone, prednisone [25%], or placebo [25%]), then all patients are treated with 2.0 or 6.0 mg/kg/day vamorolone for the next 6 months (total 1 year study). Patients completing the VBP15-004 study are offered continued access to vamorolone via an Expanded Access Protocol, or other mechanisms, as the regulations of each country permit.