by June Kinoshita, Director of Research and Patient Engagement
Fulcrum’s announcement that it will proceed with a Phase 3 clinical trial of losmapimod is big news for the FSHD community. It means that the FDA has considered the data from the Phase 2b trial (ReDUX4) and provided guidance on the design of the Phase 3 trial. From this, we can infer the Phase 2b data provided a basis for determining which outcome measures to use and the number of patients the Phase 3 trial needs in order to deliver a statistically robust finding.
Here’s what we know so far
- The trial will be called REACH
- It plans to enroll volunteers starting in the second quarter of 2022
- It will enroll around 230 adults with FSHD, ages 18-65
- Both FSHD Type 1 and Type 2 patients will be eligible
- It will be randomized and placebo-controlled, meaning that of the 230 volunteers, half will be assigned at random to receive the drug, and half will receive placebo
- It will be double-blind, meaning that neither the volunteers nor researchers will know who is getting drug vs. placebo
- The trial will be conducted at multiple international locations
- Volunteers will take a 15 mg tablet twice a day and be evaluated over a 48-week treatment period
The trial’s “primary endpoint”—the measure that the FDA will consider the most important in its decision to approve the drug—is based on Reachable Workspace (RWS). RWS is a method that uses a wireless Kinect game controller to measure how far patients can move their arms in 3D space. (Dr. Jay Han explains RWS in this video.) We surmise that RWS was chosen as the primary endpoint because it correlates strongly with activities such as self-care, work, and daily tasks—abilities that directly affect patients’ quality of life. Our Voice of the Patient Report emphasized to the FDA how important retaining these abilities is to patients.
In the Phase 2b trial, RWS showed that people on placebo lost 2-4% of their arms’ range of motion, compared with 1.5% or less in people taking losmapimod. Some individuals on losmapimod had no change or even improved. The Phase 3 trial will aim to show whether this difference in RWS holds up in the larger group of patients.
The REACH trial will also measure muscle fat infiltration (MFI) using MRI, Patient Global Impression of Change (PGIC), Quality of Life in Neurological Disorders of the upper extremity (Neuro QoL UE), and patient-centered assessments of healthcare utilization. These are “secondary endpoints,” meaning that while they are important, the trial was not designed in terms of the number of patients to show statistically significant differences on these measures.
What we don’t know yet
- Other inclusion/exclusion criteria, such as degree of impairment
- Location of trial sites
- Dates when individual sites will begin recruiting
- Whether individuals who are excluded from the Phase 3 trial will have access to losmapimod.
What can you do to be “trial ready”?
- Make sure you have joined our Research Contact Registry
- Even if you have been a part of the FSHD Society for a while, we may not have all the information we need in our database. To ensure we have the most up to date information, please complete the form!
- Have a clinically approved genetic test to confirm your FSHD diagnosis
- If you haven’t been able to get a genetic test and think you qualify for the Phase 3 trial, keep an eye out for our email announcing our genetic testing program launching in April.
What is a clinical trial?. We explain the different trial phases and factors that go into the design of a clinical trial.
ReDUX4 trial exceeds expectations. We explain Fulcrum’s Phase 2b trial results.
UC Davis seeking volunteers and UC Irvine recruiting volunteers for study. The FSHD Society helped develop the Reachable Workspace by recruiting volunteers. Many of you responded to our calls to action in 2015 and 2019. Your participation has had a huge impact!