A clinical trial of an experimental drug for ALS -- halted almost two years ago due to safety concerns –- has been given the green light to continue with a revised protocol, says CytRx Corp. of Los Angeles, the drug’s manufacturer.
The U.S. Food and Drug Administration placed a hold on the phase 2b trial of arimoclomol in January 2008, saying it wanted to see more toxicity data from previously completed animal studies. CytRx announced on Dec. 2, 2009, that it had received FDA permission to continue human testing.
The new trial is not yet officially open, but it soon will begin recruiting participants.
Arimoclomol represents a new strategy in ALS — enhancement of molecules called "chaperones," which help regulate cellular repair. According to CytRx, arimoclomol can detect proteins that are misfolded and potentially toxic and refold them into their correct, nontoxic shapes.
About the trial
The trial is funded by CytRx, with several MDA clinics and ALS centers serving as study sites. The two principal investigators are Merit Cudkowicz, director of the MDA/ALS Center at Massachusetts General Hospital in Boston; and Jeremy Shefner, director of the MDA/ALS Center at the State University of New York Upstate Medical University in Syracuse.
The new trial will test arimoclomol in groups of 20 to 30 people with ALS, starting with a dosage level of 100 milligrams three times a day, and increasing the dosage level by 75 milligrams per dose up to a maximum of 400 milligrams three times daily. An independent safety monitoring board will review results before each dosage increase.
Each group will receive arimoclomol for three months. Fifteen people will receive a combination of arimoclomol at various dose levels, plus riluzole (Rilutek), an established treatment for ALS, at a fixed dose of 50 milligrams twice daily. Another five to 15 people will receive a placebo plus 50 milligrams of riluzole twice a day.
In addition to looking at safety (the primary goal of this phase of clinical testing), the investigators will evaluate participants' scores on the revised ALS Functional Rating Scale, as well as their vital capacity (a respiratory measurement). However, the trial is designed only to note extreme responses in these two categories.
For information about the FDA’s actions, see the CytRx press release, CytRx Announces That FDA Lifts Clinical Hold of Arimoclomol in ALS (12/02/09).
SOD1 arimoclomol trial
A different phase 2-3 study of arimoclomol already is underway, focusing on the SOD1-related form of familial ALS. It was not affected by the halting of the phase 2b arimoclomol trial in ALS.
Like all experimental treatments, arimoclomol carries risks. The FDA's green light on resumption of the phase 2b trial implies that the agency believes testing this drug in ALS at this time is justified and that appropriate safeguards are in place to help protect trial participants.
Editor's note: This article was slightly modified on Jan. 29, 2010. Contact information for the phase 2b arimoclomol trial was removed, because the trial is not yet recruiting.