Phase 2b Trial Testing Vamorolone Now Enrolling Boys Ages 4-6 with DMD

José Lopes, PhD avatar

by José Lopes, PhD |

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A Phase 2b trial of the investigational therapy vamorolone is 4-to-6-year-old boys with Duchenne muscular dystrophy (DMD) has begun to enroll patients.

Patient recruitment for the international ReveraGen BioPharma-sponsored, double-blind VISION-DMD trial (NCT03439670) is now ongoing. More information on study locations and contacts can be found here. Enrollment is expected to last approximately one year.

In addition, ReveraGen and Parent Project Muscular Dystrophy will host a webinar from 1-2 p.m. EST Wednesday to provide an overview of vamorolone’s development for DMD, including previous results showing improved muscle function, and details of the current Phase 2b trial. Those who would like to listen in must register here.

The trial is expected to include approximately 120 boys who have not yet been treated with glucocorticoids at nearly 30 sites in the U.S., Canada, Israel, U.K., Sweden, Australia, the Netherlands, Belgium, and the Czech Republic. Collaborators include the EU, Newcastle University, the University of Pittsburgh, and the Cooperative International Neuromuscular Research Group. The study is expected to last for about 24 months.

Participants will be randomized to one of four groups: low-dose (2 mg/kg/day) or high-dose vamorolone (6 mg/kg/day), prednisone (0.75 mg/kg/day), or placebo. After 24 weeks of treatment, the patients on prednisone or placebo will cross over to low- or high-dose vamorolone for another 24 weeks.

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The primary outcome measures are changes in muscle function assessed by the time to stand test and body size, measured through body mass index.

Secondary measures include safety assessments — such as bone and weight changes, cataracts, glaucoma, heart rate, blood pressure, respiratory rate, body temperature, pharmacological parameters, and adverse events — as well as efficacy tests, including range of motion in the ankles, the North Star Ambulatory Assessment, which measures motor abilities in children with DMD, and analysis of knee and elbow muscle strength.

Vamorolone is a steroid product that binds to the same receptors as glucocorticoids and has a very similar chemistry and 3D structure. However, it induces less proinflammatory gene expression when bound to the receptor, which could minimize safety concerns. This makes vamorolone a so-called dissociative steroidal therapy.

Glucocorticoids prednisone and Emflaza (deflazacort) are the current standard DMD treatments, but they may cause serious side effects such as increased bone fragility, delayed puberty, mood changes, and metabolic disturbances

In DMD, the hallmark loss of the dystrophin protein destabilizes the membranes of myofibers — a type of muscle cell. Vamorolone is intended to outperform prednisolone in stabilizing myofiber membranes while inhibiting a proinflammatory protein complex known as NF-ĸB, which controls gene expression and is activated at birth in the muscles of patients with DMD.

“DMD patients need an alternative to glucocorticoid standard of care, and it is our hope that this new VISIONDMD trial will provide data towards this end,” Michela Guglieri, MD, study co-chair and honorary consultant in human genetics — neurologist at The Newcastle upon Tyne Hospitals NHS Foundation Trust, said in a press release.

In a prior open-label Phase 2a trial (NCT02760264) in 48 boys with DMD able to walk, treatment with vamorolone led to dose-dependent reductions of proinflammatory proteins and creatine kinase activity, a biomarker of muscle disease activity.

In addition, vamorolone showed an improved safety profile over prednisolone, reflected by less insulin resistance, reduced bone resorption and formation (at 6 mg/kg), and a milder decrease in adrenal suppression — determined by first-in-morning cortisol — in comparison to prior data in adult volunteers. No severe treatment-emergent adverse events were found, with none definitely related to the therapy.

“This (VISION-DMD) trial builds on the promising preliminary safety and efficacy data in our completed Phase 2a trial,” said Eric Hoffman, PhD, ReveraGen’s CEO.

Development of vamorolone involved 12 international nonprofit foundations, along with the U.S. National Institutes of Health and Department of Defense, and the European Commission Horizons 2020 program.

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