The effect of systemically administered recombinant human nerve growth factor in healthy human subjects

• Published in: Annals of neurology Vol. 36; no. 2; p. 244
• Main Authors: Petty, B G, Cornblath, D R, Adornato, B T, Chaudhry, V, Flexner, C, Wachsman, M, Sinicropi, D, Burton, L E, Peroutka, S J
• Format: Journal Article
• Language: English
• Published: United States 01.08.1994
• Subjects: Adolescent; Adult; Antibodies - analysis; Double-Blind Method; Female; Humans; Hyperalgesia - chemically induced; Injections, Subcutaneous; Male; Muscular Diseases - chemically induced; Nerve Growth Factors - administration & dosage; Nerve Growth Factors - pharmacology; Pain - chemically induced; Placebos; Recombinant Proteins - pharmacology
• ISSN: 0364-5134
• DOI: 10.1002/ana.410360221

This phase I double-masked, randomized, placebo-controlled study evaluated the safety of single intravenous or subcutaneous doses of recombinant human nerve growth factor (rhNGF) in healthy human volunteers at doses ranging from 0.03 to 1 micrograms/kg. No life-threatening adverse events were seen at any dose. At doses above 0.1 microgram/kg, subjects reported mild to moderate muscle pain, primarily in the bulbar and truncal musculature. The duration and severity of these myalgias varied in a dose-dependent manner, and women appeared to be more susceptible than men. Intravenous rhNGF produced earlier and more pronounced systemic effects than did identical subcutaneous doses. Subjects receiving subcutaneous rhNGF noted hyperalgesia at the injection site, a local effect persisting up to 7 weeks, that also varied in a dose-dependent manner. Antibodies to NGF were not detected in any subject. These results indicate that systemically administered rhNGF exerts a characteristic and reproducible biological effect in healthy subjects at very low doses and in a dose-dependent manner.