New Phase 2b Trial of Tirasemtiv (CK-2017357) in ALS

Update (Oct. 29, 2012): This article has been updated to reflect the fact that the trial is now open to recruitment.

South San Francisco biotechnology company Cytokinetics announced Sept. 10, 2012, that it plans to conduct a new phase 2b clinical trial of its oral drug tirasemtiv (formerly CK-2017357) in people with amyotrophic lateral sclerosis (ALS). The trial is set to launch later this year.

On Oct. 29, the company announced in a press release that the trial is now open to recruitment.

The new trial marks the fourth phase 2 trial for tirasemtiv, Cytokinetics' leading drug candidate for ALS. The first, second and third phase 2 trials, which have been completed, had different study designs from the new trial.

"We are pleased to further evaluate tirasemtiv in patients with ALS, building upon our prior clinical experience obtained in trials of shorter duration," Andrew A. Wolff, Cytokinetics’ senior vice president of clinical research and development and chief medical officer, said in a press release. "Our recent interactions with regulatory authorities in the United States and Europe have informed this progress to the next stage of clinical development for tirasemtiv."

The U.S. Food and Drug Administration (FDA) granted tirasemtiv orphan drug status March 10, 2010. (Orphan drug status provides financial incentives for the development of drugs for rare diseases.)

About the new trial

The new phase 2b trial is designed to evaluate the safety, tolerability and efficacy (how well the therapy works) of tirasemtiv in people with ALS.

Approximately 400 trial participants at study sites in the United States and Europe will be randomly assigned to one of two groups. Those in the treatment group will receive twice-daily doses of tirasemtiv for three months, while those in the control group will receive an inactive substance (placebo). Those who are taking riluzole (brand name Rilutek) at the time of enrollment and who are assigned to the treatment group will receive riluzole at a daily dose of 50 milligrams.

Investigators will measure changes in motor function using the ALS Functional Rating Scale-Revised (ALSFRS-R), a validated ratings scale used by physicians to assess symptom progression in people with ALS. The team also will evaluate measurements of pulmonary, respiratory and skeletal muscle function.

Building on encouraging results

Tirasemtiv is thought to increase the sensitivity of muscle fibers to calcium, resulting in a potential increase in muscle force generation. (To read a manuscript describing Tirasemtiv's mechanism of action, visit the Cytokinetics home page and click on the Nature Medicine paper on activation of fast skeletal muscle troponin under "Recent Scientific Publications.")

Data from two completed phase 2 clinical trials were presented at the April 2012 American Academy of Neurology (AAN) Annual Meeting in New Orleans.

In one of the two trials, tirasemtiv was tested first in people with ALS who were not receiving riluzole, and then in a group of people with ALS who received riluzole at a dose of 50 milligrams per day. The drug appeared to be generally safe and well-tolerated, with no major differences noted between those who received riluzole and those who did not. Although the trial was not designed to evaluate the efficacy of tirasemtiv, analysis suggested encouraging trends in muscle and pulmonary function.

In the second phase 2 trial, a twice-daily dose of tirasemtiv also appeared to be generally safe and well-tolerated. The majority of trial participants safely took tirasemtiv at a dose of 250 milligrams two times per day. As with the first trial, this trial was not designed to evaluate the effects of tirasemtiv on the various outcome measures, but positive trends were seen in motor and pulmonary function. 

Data from an earlier phase 2a clinical trial that evaluated single doses of tirasemtiv were presented in December 2010 at the 21st International Symposium on ALS/MND in Orlando, Fla. In all three previous phase 2 trials, tirasemtiv was found to be safe and well-tolerated. In addition, it has demonstrated encouraging trends to improvement in functional abilities, and in measures of respiratory and skeletal muscle strength and endurance in trial participants.

To participate

As of Oct. 29, 2012, the phase 2b study of tirasemtiv (formerly CK-2017357) is open to approximately 400 men and women with ALS who are at least 18 years old and meet other study criteria. See Study of Safety, Tolerability & Efficacy of CK-2017357 in Amyotrophic Lateral Sclerosis (ALS), or enter NCT01709149 in the search box at, or contact Jean Masonek at

About Clinical Trials

About Clinical Trials

A clinical trial is a test, in humans, of an experimental treatment. Although it's possible that benefit may be derived from participating in a clinical trial, it's also possible that no benefit, or even harm, may occur.

MDA has no ability to influence who is chosen to participate in a clinical trial.

To learn more, see Understanding Clinical Trials and Being a Co-Adventurer, which is about neuromuscular disease clinical trials. To see a continuously updated database of clinical trials, go to

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