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Address correspondence to Dr Cedarbaum, Regeneron Pharmaceuticals, Inc., 777 Old Saw Mill River Rd., Tarrytown, NY 10591.
Ciliary neurotrophic factor (CNTF) is a neuroactive cytokine found in Schwann cells, which appears to be released in response to nerve injury. The ALS CNTF Treatment Study (ACTS) clinical trial was a phase II-III randomized, placebo-controlled, double-blind study designed to evaluate the safety, tolerability, and efficacy of subcutaneous administration of recombinantly produced human CNTF (rHCNTF) in slowing disease progression in 730 patients with amyotrophic lateral sclerosis (ALS). Patients were randomized to receive 30 µg/kg or 15 µg/kg rHCNTF or placebo subcutaneously three times a week for 9 months. The primary endpoint of the study, the slope of decline of isometric muscle strength in treated versus placebo patients, showed no statistically significant difference between rHCNTF and placebo-treated patients, and was complicated by an initial statistically significant decrease in strength early in rHCNTF-treated patients. Mortality was similar in all three study arms. There were no statistically significant treatment effects among the secondary measures. Side effects of rHCNTF included anorexia, weight loss, and cough and were sufficient to limit dosing in many patients.
This study was funded in its entirety by a grant from Regeneron Pharmaceuticals, Inc. Several individuals involved in the conduct of the study, including members of the Data Safety Monitoring Board and the staff of the Data Management and Analysis Center, were paid consultants or were otherwise under contract to Regeneron Pharmaceuticals or were receiving research support outside of the clinical trial from Regeneron. None of the study participants, other than employees of Regeneron Pharmaceuticals, Inc., were permitted to hold stock in Regeneron Pharmaceuticals during the time the study was ongoing.
Address reprint requests to Dr. Benjamin R. Brooks, ALS Clinical Research Center, Department of Neurology, University of Wisconsin Medical Center, Madison, WI 53792.
Received September 6, 1995. Accepted in final form October 10, 1995.
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