INTRANASALLY APPLIED RECOMBINANT LEUKOCYTE-A INTERFERON IN NORMAL VOLUNTEERS .2. DETERMINATION OF MINIMAL EFFECTIVE AND TOLERABLE DOSE

In an attempt to find a dose of recombinant leukocyte A interferon (rIFN-.alpha.A) that is both efficacious against rhinovirus challenge and is tolerable, double-blind, placebo-controlled studies were performed; 56 normal volunteers received either placebo or 1 of 2 relatively small doses of rIFN-.alpha.A (i.e., 2.4 .times. 106 U [2.4 M] or 0.7 .times. 106 .+-. [0.7 M]/day) for 4 days. The frequency of illness was significantly lower in the group given doses of 2.4 M than in a group of volunteers given placebo (29% vs. 73%; P < 0.032); the frequencies of illness in the group given doses of 0.7 M and in a placebo group were similar (67% vs. 63%). The rates of infection in these pairs of groups were not significantly different from each other. No significant local or systemic reactions were noted during the 4 days of rIFN-.alpha.A administration. In a 26-day tolerance study, 15% of volunteers given 2.4 M doses of rIFN-.alpha.A developed bloody mucus and nasal mucosal erosions, while no such local reactions were noted in volunteers given 0.7 M doses or in those given placebo. Thus, increasing doses of rIFN-.alpha.A were associated with both increasing efficacy against rhinovirus-induced illness and increasing frequency of local adverse reactions.