The double-blind, placebo-controlled trial is expected to require nine months to complete enrollment of approximately 390 amyotrophic lateral sclerosis (ALS) volunteers at 30 to 40 US and Canadian clinical sites, and will evaluate the safety and efficacy of 400mg arimoclomol administered orally three times daily for a nine-month period. In order to maximize the amount of long-term safety and efficacy data from this trial, CytRx will continue double-blind arimoclomol administration for an additional nine months after collection of primary endpoint data to collect additional data on secondary endpoints.
The Phase IIb trial’s primary endpoint will be efficacy after nine months of dosing as determined by the revised ALS Functional Rating Scale (ALSFRS-R), which is used to determine a patient’s capacity and independence in 13 functional activities. Secondary Phase IIb efficacy endpoints include ALSFRS-R at 18 months and survival at 18 months, as well as pulmonary function, muscle strength, Motor Unit Number Estimate (MUNE) (a non-invasive test that estimates the number of functioning motor units), and quality of life, all of which will be measured at nine and 18 months.
The trial is designed in two tiers, both of which will receive the same dose for the same length of time. The first tier will enroll 24 ALS volunteers and will have a four-week safety lead-in phase designed with weekly clinical monitoring to assure that the safety previously observed in healthy volunteers is also observed in ALS volunteers. After the initial four weeks, dosing will continue uninterrupted and clinical monitoring will be reduced for the remainder of the study. Safety data from the first four-week period of Tier I will be reviewed by an independent data monitoring committee and, if no serious safety issues are identified, the remainder of the ALS volunteers will be enrolled without this safety lead-in phase (Tier II). With the exception of the first four weeks of Tier I, all 390 ALS volunteers enrolled in the Phase IIb trial will be followed every four weeks for the first nine months and every eight weeks for the remaining nine month trial period.
Jack Barber, chief scientific officer of CytRx, said: “We have taken multiple steps to maximize the probability of measuring efficacy in the Phase IIb clinical trial, including administering arimoclomol at a significantly higher dose than that used in our Phase IIa trial.”