Cytokinetics revealed preliminary data on the characteristics of patients with spinal muscular atrophy (SMA) screened for a Phase 2 trial to investigate the safety, tolerability and pharmacokinetics of CK-2127107.
Data were presented by Cytokinetics’ director of clinical research, Stacy Rudnicki, MD, at the Cure SMA 2017 Annual SMA Conference in Orlando, Florida.
The Phase 2 trial (NCT02644668) is an exploratory and hypothesis-generating study designed to include two groups of SMA patients (types II, III and IV) — cohort 1 and cohort 2. Patients will be assigned either CK-2127107 or a placebo. Data presented at the SMA meeting referred to patients in cohort 1.
The study planned to enroll 18 ambulatory patients (who maintain the ability to walk) with SMA types III or IV, as well as 18 non-ambulatory patients, with type II or III SMA. Enrolled patients are 12 years or older. Those assigned to the CK-2127107 group, in cohort 1, will first receive the drug in a suspension formulation and then oral doses (150 mg, twice daily) for eight weeks. Those assigned to placebo are dosed in the same regimen.
Patients in cohort 2 will be randomized to receive either CK-2127107 (450 mg) or a placebo, twice daily for eight weeks.
The trial includes the analysis of muscular function, fatigue and respiratory capacity. Ambulatory patients also will be tested in the six-minute walk (a measure of the respiratory capacity) and timed-up-and-go tests (measuring a person’s motility and balance); non-ambulatory patients will be tested for functionality and arm strength. All patients in this cohort also will be able to report their outcomes with the SMA Health Index.
According to the data presented at the meeting on the characteristics of patients screened for cohort 1:
- SMA patients had a mean age of 27.7 years;
- SMA patients had the disease for 22.2 years and a confirmed diagnosis for 11.6 years;
- 19 patients were ambulatory, all with SMA type III, whereas 20 patients (15 with SMA type III and five with SMA type II) were non-ambulatory;
- In terms of respiratory capacity, on average, patients had a forced vital capacity (FVC) of 84 percent of predicted, a maximal expiratory pressure (MEP) of 88.7 cm H2O and a maximal inspiratory pressure (MIP) of -99.4 cm H2O;
- compared to non-ambulatory patients, ambulatory patients presented a better score on motor measurements, such as the Hammersmith Functional Motor Scale Expanded (HFMSE, 18.9 versus 48.8, respectively) and the Revised Upper Limb Module (RULM, 28 versus 39.27, respectively);
- ambulatory patients also scored 17.7 seconds in the timed-up-and-go and 290.7 meters in the six-minute walk tests.
- Not all patients met the inclusion criteria for the study. The main reason was an HFMSE score that was too increased in walking patients, or too decreased in non-walking patients. No other differences were found between the enrolled patients.
“The baseline demographics we observed in Cohort 1 are consistent with our expectations for the patient population targeted in this first Phase 2 clinical trial of CK-2127107,” Fady I. Malik, MD, PhD and executive vice president of Research and Development at Cytokinetics, said in a press release. “Adolescent and adult patients with SMA have previously had limited opportunities to participate in clinical trials and we are pleased to be gaining real-world insights into how to optimize design and inclusion criteria for future trials that may enroll this growing patient population.”
CK-2127107 has been granted Orphan Drug designation by the Food and Drug Administration (FDA) as a potential treatment for SMA.