Clinical and Biological Effects of Recombinant Interferon-β Administered Intravenously Daily in Phase I Trial

Abstract

Interferon-β serine (IFN-β_ser) was administered intravenously (i.v.) daily for 14 days at doses of 3, 10, 30 x 10⁶ units to 19 patients. In this Phase I trial, IFN-γ_ser was tolerated without limiting fever or subjective toxicities. At 30 x 10⁶ units, 3 patients developed hematologic toxicity and dose escalation was thus terminated. No patient developed detectable binding or neutralizing antibody to IFN-β. A significant (p < 0.006) increase in serum β₂-microglobulin and a significant ( < 0.005) increase in 2′, 5′-oligoadenylate synthetase (2-5A) in peripheral mononuclear cells were identified. Increase in these proteins did not correlate with dose or with the disappearance of serum IFN over the first 5 h after injection. Two patients, one with renal carcinoma and one with melanoma, had objective responses. This trial further confirms safety and biological potency of this synthetic mutant of IFN-β.