A PLACEBO-CONTROLLED TRIAL OF RECOMBINANT HUMAN CILIARY NEUROTROPHIC (RHCNTF) FACTOR IN AMYOTROPHIC-LATERAL-SCLEROSIS

Preclinical investigations indicated that recombinant human ciliary ne urotrophic factor (rhCNTF) may have potential as therapy for amyotroph ic lateral sclerosis (ALS). We evaluated the safety and efficacy of rh CNTF in a prospective, double-blind, placebo-controlled trial in 570 p atients with ALS. Patients were randomized to receive 0.5, 2, or 5 mu g/kg/day rhCNTF, or placebo, for 6 months. The primary efficacy end po int was the change from baseline to the last on-treatment value of a c ombination meg ascore for limb strength (maximum voluntary isometric c ontraction) and pulmonary function. Secondary end points included indi vidual arm and leg megascores, pulmonary function tests, an activities -of-daily-living outcome measure, and survival. The four treatment gro ups were similar at baseline with respect to age, sex, disease duratio n, and muscle strength values. At all doses tested, rhCNTF had no bene ficial effect on the primary or secondary end points. Certain adverse events, as follows, appeared to be dose related: injection site reacti ons, cough, asthenia, nausea, anorexia, weight loss, and increased sal ivation. There was an increased number of deaths at the highest dose l evel. rhCNTF had no benefical effect on any measure of ALS progression . There were increased adverse events in the 5 mu g/kg group and incre ased deaths.