The Phase 2 FORTITUDE-ALS (NCT03160898) study will soon be recruiting 450 eligible ALS patients from centers in the United States and Canada to evaluate the change from baseline in the percent predicted slow vital capacity (SVC), a measure of the strength of respiratory muscles, and other measures of skeletal muscle function after treatment with CK-2127107.
Participants will be randomized equally into four groups to receive 150 mg, 300 mg, or 450 mg of CK-2127107 twice daily, or a placebo, for 12 weeks. Researchers will also explore the effect of CK-2127107 in self-assessed respiratory function, speech, handwriting abilities, and quality of life.
CK-2127107 is a next-generation fast skeletal muscle troponin activator (FSTA) designed to slow down calcium release, leading to an increase in skeletal muscle contractility. The motor protein responsible for converting chemical energy into mechanical force is called skeletal muscle myosin, which interacts with the protein actin. This actin-myosin interaction is dependent on changes in intracellular calcium levels, which is why CK-2127107 targets calcium release.
According to Cytokinetics, in nonclinical models of SMA, a skeletal muscle activator was shown to increase skeletal muscle force and power, delay the onset of disease, and reduce the degree of muscle fatigue.
The U.S. Food and Drug Administration granted CK-2127107 orphan drug designation for spinal muscular atrophy (SMA), which also is associated with skeletal muscle degeneration.
CK-2127107 is being developed by Cytokinetics in collaboration with Astellas Pharma. The primary goal of the alliance is to advance new therapies for diseases and conditions associated with muscle degeneration.
“Starting FORTITUDE-ALS reflects our increased commitment to explore the potential of our muscle-biology directed investigational therapies for the potential treatment of people with ALS,” Fady I. Malik, MD, PhD, Cytokinetics’ executive vice president of research and development, said in a press release.
“Under our collaboration with Astellas, we look forward to now exploring the potential of this next-generation FSTA in a fourth patient population in which it may alter the decline of muscle function and performance. This clinical trial offers an opportunity to assess exploratory measures of patient function that may also prove informative in further quantifying ALS disease progression,” Malik added.
Also included in the Cytokinetics-Astellas collaboration is the development of Cytokinetics’ lead therapy candidate, tirasemtiv, also an FSTA, for the treatment of ALS. Tirasemtiv has received orphan drug and fast-track designations by the FDA and orphan medicinal product designation by the European Medicines Agency (EMA) for the potential treatment of ALS.