STARFISH PIER: Study of Testosterone and rHGH in FSHD: Planning Infrastructure Execution and Readiness - PROJECT SUMMARY/ABSTRACT: Facioscapulohumeral muscular dystrophy (FSHD) is the second most common adult muscular dystrophy in the world with a global prevalence of ~4:100,000. Clinically, patients with FSHD experience progressive weakness, muscle wasting, and varied symptomatic burden. As adult patients with FSHD age, they frequently develop difficulty walking or lose the ability to ambulate due to profound weakness and muscle atrophy. Currently, there are no therapies that have been demonstrated to reverse or even slow the progressive symptoms associated with FSHD. A treatment that limits disease progression and/or reverses functional decline would be beneficial to this population. In 2022, we successfully completed a single center (University of Rochester), single-arm, proof-of-concept study to evaluate the safety and tolerability of daily rHGH (Genotropin®) combined with testosterone enanthate injections every 2 weeks in men with FSHD. Participants received study drugs for 24 weeks followed by a 12-week washout period. Participants received serial safety testing, laboratory testing, functional assessments, and disease burden monitoring during the study with no participants experiencing a serious adverse event. After 24 weeks, the six-minute walk distance increased by 37.3 meters (p=0.001), lean body mass improved by 2.2 kg (p<0.0001), body fat reduced by 1.3 kg (p=0.044), overall strength (standardized QMT, average % of predicted normal) increased by 3% (p=0.033), clinical function (FSHD-COM) improved by 12% (2.4 points; p=0.006), and total disease burden (FSHD-HI) reduced by 19% (6 points; p=0.043) from baseline. While this approach generated one of the largest gains of function in response to a therapy in FSHD, a larger placebo-controlled efficacy study is needed to further validate these results. The proposed one-year planning award allows for the completion of all of the preliminary steps needed to successfully initiate and eventually conduct such a study. Planning award activities will include but will not be limited to: 1) finalizing the study protocol, statistical analysis plan, data and safety monitoring plan, and all required study materials; 2) securing pharmaceutical contracts for study drugs; 3) identifying and securing partnerships with external collaborators and clinical sites; 3) initiating the IRB approval process; and, 4) applying for a NIAMS U01 clinical trial award to support the implementation and conduct of a multicenter phase 3 study. Ultimately, this phase 3 study will evaluate an extremely promising therapeutic approach for improving ambulation, strength, lean body mass, and symptomatic burden in a well-defined cohort of patients with FSHD and will pave the way for FDA approval of a potentially life-improving therapy for patients with this muscular dystrophy.
