Cytokinetics (CYTK) Reports Positive CK-2017357 Phase II, Part A Dat in ALS Patients
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Cytokinetics, Incorporated (Nasdaq: CYTK) reports positive results from the first cohort, or Part A, of a continuing Phase II clinical trial of CK-2017357 in patients with amyotrophic lateral sclerosis (ALS). Data were presented at the 22nd International Symposium on ALS/MND in Sydney, Australia.
A poster titled "A Study to Evaluate Safety, Tolerability and Clinical Outcomes Following Repeated Doses of CK-2017357 in Patients with Amyotrophic Lateral Sclerosis" was presented by Jeremy M. Shefner, MD, PhD, Professor and Chair of the Department of Neurology at the Upstate Medical University at the State University of New York. The poster summarized data from Part A of this ongoing Phase II clinical trial. CK-2017357 selectively activates the fast skeletal muscle troponin complex by increasing its sensitivity to calcium, which increases skeletal muscle force in response to neuronal input and delays the onset and reduces the degree of muscle fatigue. CK-2017357 is the lead drug candidate from the company's skeletal muscle contractility program.
Phase II Clinical Trial Results From Part A
Part A of this Phase II clinical trial successfully met its primary objective of defining the tolerability and pharmacokinetic profile of CK-2017357 during two weeks of daily dosing in 24 ALS patients who were not taking riluzole concurrently. CK-2017357 was well-tolerated as a single agent at all dose levels from 125 mg daily to 375 mg daily for two weeks in these patients.
In Part A of this trial, 83% of patients in the combined CK-2017357 dose groups reported at least one treatment-emergent adverse event, compared with 67% of the patients receiving placebo. In the combined dose groups receiving CK-2017357, the most common and dose-related side effect reported was dizziness, observed in no patients receiving placebo and 8 of the 18 patients receiving CK-2017357. The dizziness did not persist beyond the second day of dosing in all but one of the patients studied. A total of 14 episodes of dizziness were reported, 12 of which were mild in severity. The incidence of dizziness appeared dose-related and self-limiting in all patients who completed study drug treatment except for one patient in whom it was mild in severity. Two patients withdrew early, both due to treatment-emergent dizziness. No serious adverse events were reported.
Plasma concentrations of CK-2017357 increased with escalating doses; however, there was considerable overlap between the dose groups in the range of observed plasma levels. As expected, due to the small sample size of 24 patients, the large inter-patient variability and the short, two-week duration, Part A of this trial lacked the statistical power to detect significant differences in clinical outcome measures. However, trends to improved clinical outcome measures were observed, especially at the highest CK-2017357 dose of 375 mg daily. Four of five patients who completed treatment in this dose group reported improvement in their Global Assessments and three of these five patients improved at least 1 point on the ALS Functional Rating Scale-Revised (ALSFRS-R). The changes observed in Maximum Voluntary Ventilation (MVV) after two weeks of dosing at 375 mg compare favorably to improvements observed at 24 hours after a single 500 mg dose of CK-2017357 in the prior Phase IIa Evidence of Effect clinical trial in ALS patients. Additional analyses from this ongoing clinical trial, including results from efficacy outcome measures, are expected to be presented at a later date.
Phase II Clinical Trial Design
This ongoing Phase II clinical trial is a double-blind, randomized, placebo-controlled trial designed to evaluate the safety and tolerability of multiple doses of CK-2017357 in patients with ALS. In Part A, 24 ALS patients who were not currently taking riluzole were randomized to one of four different treatment groups to receive daily oral doses of placebo or 125 mg, 250 mg, or 375 mg of CK-2017357, respectively, for two weeks. Clinical assessments took place at pre-determined times during the course of treatment. Patients also participated in follow-up evaluations one week after their final dose. Cytokinetics recently announced the initiation of a second cohort, or Part B, of this trial in 24 patients with ALS who are receiving riluzole.
The primary objective of this clinical trial is to assess the safety and tolerability of CK-2017357, after multiple oral doses to steady state plasma concentrations, in patients with ALS. A secondary objective of this clinical trial is to evaluate the ALSFRS-R, other measures of pulmonary function, muscle strength and fatigue, and physician and patient global assessments in these patients while receiving two weeks of treatment with CK-2017357 at the indicated doses or placebo.
A poster titled "A Study to Evaluate Safety, Tolerability and Clinical Outcomes Following Repeated Doses of CK-2017357 in Patients with Amyotrophic Lateral Sclerosis" was presented by Jeremy M. Shefner, MD, PhD, Professor and Chair of the Department of Neurology at the Upstate Medical University at the State University of New York. The poster summarized data from Part A of this ongoing Phase II clinical trial. CK-2017357 selectively activates the fast skeletal muscle troponin complex by increasing its sensitivity to calcium, which increases skeletal muscle force in response to neuronal input and delays the onset and reduces the degree of muscle fatigue. CK-2017357 is the lead drug candidate from the company's skeletal muscle contractility program.
Phase II Clinical Trial Results From Part A
Part A of this Phase II clinical trial successfully met its primary objective of defining the tolerability and pharmacokinetic profile of CK-2017357 during two weeks of daily dosing in 24 ALS patients who were not taking riluzole concurrently. CK-2017357 was well-tolerated as a single agent at all dose levels from 125 mg daily to 375 mg daily for two weeks in these patients.
In Part A of this trial, 83% of patients in the combined CK-2017357 dose groups reported at least one treatment-emergent adverse event, compared with 67% of the patients receiving placebo. In the combined dose groups receiving CK-2017357, the most common and dose-related side effect reported was dizziness, observed in no patients receiving placebo and 8 of the 18 patients receiving CK-2017357. The dizziness did not persist beyond the second day of dosing in all but one of the patients studied. A total of 14 episodes of dizziness were reported, 12 of which were mild in severity. The incidence of dizziness appeared dose-related and self-limiting in all patients who completed study drug treatment except for one patient in whom it was mild in severity. Two patients withdrew early, both due to treatment-emergent dizziness. No serious adverse events were reported.
Plasma concentrations of CK-2017357 increased with escalating doses; however, there was considerable overlap between the dose groups in the range of observed plasma levels. As expected, due to the small sample size of 24 patients, the large inter-patient variability and the short, two-week duration, Part A of this trial lacked the statistical power to detect significant differences in clinical outcome measures. However, trends to improved clinical outcome measures were observed, especially at the highest CK-2017357 dose of 375 mg daily. Four of five patients who completed treatment in this dose group reported improvement in their Global Assessments and three of these five patients improved at least 1 point on the ALS Functional Rating Scale-Revised (ALSFRS-R). The changes observed in Maximum Voluntary Ventilation (MVV) after two weeks of dosing at 375 mg compare favorably to improvements observed at 24 hours after a single 500 mg dose of CK-2017357 in the prior Phase IIa Evidence of Effect clinical trial in ALS patients. Additional analyses from this ongoing clinical trial, including results from efficacy outcome measures, are expected to be presented at a later date.
Phase II Clinical Trial Design
This ongoing Phase II clinical trial is a double-blind, randomized, placebo-controlled trial designed to evaluate the safety and tolerability of multiple doses of CK-2017357 in patients with ALS. In Part A, 24 ALS patients who were not currently taking riluzole were randomized to one of four different treatment groups to receive daily oral doses of placebo or 125 mg, 250 mg, or 375 mg of CK-2017357, respectively, for two weeks. Clinical assessments took place at pre-determined times during the course of treatment. Patients also participated in follow-up evaluations one week after their final dose. Cytokinetics recently announced the initiation of a second cohort, or Part B, of this trial in 24 patients with ALS who are receiving riluzole.
The primary objective of this clinical trial is to assess the safety and tolerability of CK-2017357, after multiple oral doses to steady state plasma concentrations, in patients with ALS. A secondary objective of this clinical trial is to evaluate the ALSFRS-R, other measures of pulmonary function, muscle strength and fatigue, and physician and patient global assessments in these patients while receiving two weeks of treatment with CK-2017357 at the indicated doses or placebo.
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