CytRx has been permitted to re-enter the clinic with its orally administered molecular chaperone drug candidate Arimoclomol as a therapeutic treatment for amyotrophic lateral sclerosis (ALS or Lou Gehrig’s disease), following the FDA acceptance of a revised clinical trial protocol.
The company said that the clinical trial protocol accepted by the FDA is a tiered, placebo-controlled, double-blind ascending dose study. The study is designed to test progressive groups each with between 20 and 30 ALS patients over a three-month treatment period.
Fifteen patients will receive a combination of Arimoclomol at various dose levels and Riluzole at a fixed dose of 50mg twice daily, with between five and 15 ALS patients receiving placebo and Riluzole at the same fixed dose. The first group will receive Arimoclomol 100mg capsules three times daily.
For every four weeks, another group of ALS patients will begin three-month testing with six patients receiving Arimoclomol dosing three times daily at a 75mg per dose increase from the prior group. The maximum dose in the protocol allows for testing arimoclomol is at 400mg three times daily. An independent safety monitoring board will review safety results prior to initiating each consecutive increase in dosage level.
The trial’s endpoints include a preliminary evaluation of efficacy using two widely accepted surrogate markers, the revised ALS Functional Rating Scale (ALSFRS-R), which is used to determine patient’s capacity and independence in 13 functional activities, and vital capacity (VC), an assessment of lung capacity. The trial is powered to monitor only extreme responses in these two categories.
Reportedly, in August 2009, CytRx reported that Arimoclomol had exhibited both neuroprotective and neuroregenerative effects in brain cells of animals induced with stroke, offering insights into its mechanism of action.
Daniel Levitt, chief medical officer of CytRx, said: “The revised protocol allows for a safety assessment and a preliminary efficacy evaluation in ALS patients treated with arimoclomol at levels up to four times the dose administered in prior Phase IIa clinical trial and open label extension study.
“Arimoclomol will be administered in combination with riluzole (Rilutek), the only currently FDA-approved treatment for ALS, which typically prolongs life by approximately two months. We currently estimate that data from this trial, should all tiers be completed, will be available approximately 18 months from the time the trial starts.”