A Potential Steroid Alternative Customized for Duchenne
Questions and Answers
What stage is this research?
Vamorolone is a multi-functional drug that shows anti-inflammatory, membrane stabilization, and mineralocorticoid receptor antagonist activities. While it is a steroidal drug, it is not a corticosteroid, and current data suggest that it does not lead to some of the side effects associated with corticosteroids in DMD (deflazacort, prednisone), such as growth stunting. Open label Phase 2 studies (VBP15-002; VBP15-003) have been completed in 46 DMD boys, and the data obtained suggested improvements in strength and mobility over a 6-month treatment period. 43 of these boys enrolled in a 2-year long-term extension study (VBP15-LTE); some have completed the LTE and enrolled in Expanded Access for continued vamorolone treatment. Currently, boys with DMD are being enrolled in the pivotal clinical trial (VBP15-004; Phase 2b/3), the trial requested by the FDA that was designed to get critical information about how vamorolone is working (efficacy) in order to file for drug approval. During the first 6 months of this trial, one quarter of the boys will receive a placebo, one quarter will receive prednisone, and half will receive vamorolone (either 2 mg/kg/day or 6 mg/kg/day). After 6 months, ALL of the boys will transition to vamorolone. Upon finishing the trial, there is an Expanded Access Program available so participants can continue to receive vamorolone. We are enrolling 120 boys with Duchenne (4 to 6 years, steroid naïve); we plan to complete enrollment by the end of 2019. This study is recruiting at about 30 sites in the following countries: US, CANADA, UNITED KINGDOM, ISRAEL, AUSTRALIA, SWEDEN, NETHERLANDS, CZECH REPUBLIC, BELGIUM, SPAIN, GREECE.
Other trials that are finished or ongoing:
- A Phase 2a clinical trial (VBP15-002) of 48 Duchenne boys (4 to 6 years old, steroid naïve) is complete. This was a 2- week treatment trial, with a focus on safety and biomarkers. This study has been published.
- A Phase 2a extension clinical trial (VBP15-003) in Duchenne boys is also complete. Boys received 6 months of treatment with vamorolone; 46 of the 48 boys who enrolled in VBP15-002 entered and finished this study. The study showed that vamorolone was safe up to the highest dose (6 mg/kg) and showed dose-responsive improvements in strength and mobility measures.
- The Long Term Extension study (VBP15-LTE) is a 2-year continuation study of the same boys who were enrolled in VBP15-003, with all boys increasing vamorolone dose to 2.0-6.0 mg/kg/day. At the time of writing, 43 boys continue in or have finished this study; no one has withdrawn from the trial due to a safety concern. In this trial, we are evaluating the long-term safety of vamorolone, and comparing safety to boys treated with prednisone in a natural history study.
- Expanded access is available for participants who have finished vamorolone trials and wish to continue vamorolone treatment. We are continuing to monitor long-term safety of vamorolone during expanded access.
What is the goal or purpose of this research study?
The goal of this research is to see if vamorolone (an investigational drug) is effective (improves or stabilizes muscle strength and function) and safe in boys with Duchenne.
Vamorolone is being developed as a potential replacement for corticosteroids (deflazacort, prednisone); it is not used in combination with corticosteroids.
If trials show that vamorolone is safe and effective, it could potentially be approved for DMD.
Who is funding this research study?
Many non-profit foundations and governments have funded the vamorolone program. A complete description of funders can be found at http://www.reveragen.com/about-us/partnerships/
The National Institute of Neurological Disorders and Stroke (1R44NS095423-01) and the National Institute of Arthritis and Musculoskeletal and Skin Diseases (1U34AR068616-01) have provided funding for VBP15-002, VBP15-003, and VBP15-004 trials.
The European Union’s Horizon 2020 research and innovation program under grant agreement No 667078 has provided funding for VBP15-004 (via Newcastle University, UK).
To date, ReveraGen has worked through public-private partnerships to develop other aspects of the vamorolone development program:
- PPMD ($750,000) and Foundation to Eradicate Duchenne ($250,000) have co-funded the chronic toxicology studies
- MDA USA, and three UK foundations (Joining Jack, Duchenne Research Fund, Duchenne Children’s Trust) provided $2M for the Phase 1 trial.
- Additional funding has provided by the Save Our Sons, NIH TRND, CDMRP Department of Defense, CureDuchenne, and the Duchenne Alliance Research Foundation (Save Our Sons, Michael’s Cause, Pietro’s Fight, Alex’s Wish, and Ryan’s Quest).
- Grants for design of a clinical trial in younger (2-4 year) and older (8-18 year) DMD boys has been provided by DuchenneUK and Save Our Sons.
ReveraGen has received funding via option agreements with Actelion, Idorsia and Santhera.
Who is eligible to participate in this research study?
Boys with Duchenne who have never taken steroids and who are ages 4, 5, or 6 at study entry.
Additional eligibility criteria may apply and can be discussed with a study team member.
How long will this research study last, and will I have access to the investigational drug once the study has ended?
The currently recruiting VBP15-004 study is a 1-year study for each patient enrolled.
After completion of the study, participants may continue to receive vamorolone via ReveraGen’s Expanded Access Program, under IND (see clinicaltrials.gov, NCT03863119) in the US, or possibly via compassionate use in other countries.
Where does this research study take place?
The actively recruiting VBP15-004 study will take place at sites located in the USA, Canada, Europe, Israel, and Australia.
Detailed site information can be found on clinicaltrials.gov (NCT03439670).
How many visits to the study site are necessary?
Approximately 15 visits over about 12 months. There are no mandated site visits for the Expanded Access Program, but your child must continue to receive regular clinical care with visits to the physician prescribing vamorolone.
All drug dosing is taken by mouth and is taken each morning at home. Vamorolone is a flavored liquid suspension.
Can any visits be done locally?
Visits for the VBP15-004 trial must be done at one of the participating sites.
Will I get paid for participating in this research study?
No, but travel, stay, and meal expenses are paid for by the study.
Why should I consider participating in this research study?
Participation will help determine whether vamorolone is a safe and effective therapy for Duchenne.
If vamorolone is shown to be safe and effective for Duchenne, vamorolone may be available to other children with Duchenne instead of corticosteroids. If vamorolone is safe and effective in Duchenne, this could lead to other studies of vamorolone in disorders where corticosteroids are used.
The vamorolone program includes many innovations in clinical trial design that, if successful, may speed other drug development programs, including blood biomarkers and mobile health outcomes.
ReveraGen is focused on keeping patients at the center, providing continued access to vamorolone for trial participants.
Where can I learn more about this research study?
You can learn more about this study at https://vision-dmd.info/ or www.reveragen.com, or www.clinicaltrials.gov.
For parent queries, contact Suzanne Gaglianone at Suzanne.firstname.lastname@example.org; for physician queries contact Laurie Conklin, MD at email@example.com