title: Preliminary clinical findings on NEUMUNE as a potential treatment for acute radiation syndrome.
abstract: 5-androstenediol (5-AED) has been advanced as a possible countermeasure for treating the haematological component of acute radiation syndrome (ARS). It has been used in animal models to stimulate both innate and adaptive immunity and treat infection and radiation-induced immune suppression. We here report on the safety, tolerability and haematologic activity of 5-AED in four double-blinded, randomized, placebo-controlled studies on healthy adults including elderly subjects. A 5-AED injectable suspension formulation (NEUMUNE) or placebo was administered intramuscularly as either a single injection, or once daily for five consecutive days at doses of 50, 100, 200 or 400 mg. Subjects (n = 129) were randomized to receive NEUMUNE (n = 95) or the placebo (n = 34). NEUMUNE was generally well-tolerated; the most frequent adverse events were local injection site reactions (n = 104, 81%) that were transient, dose-volume dependent, mild to moderate in severity, and that resolved over the course of the study. Blood chemistries revealed a transient increase (up to 28%) in creatine phosphokinase and C-reactive protein levels consistent with intramuscular injection and injection site irritation. The blood concentration profile of 5-AED is consistent with a depot formulation that increases in disproportionate increments following each dose. NEUMUNE significantly increased circulating neutrophils (p < 0.001) and platelets (p < 0.001) in the peripheral blood of adult and elderly subjects. A dose-response relationship was identified. Findings suggest that parenteral administration of 5-AED in aqueous suspension may be a safe and effective means to stimulate innate immunity and alleviate neutropenia and thrombocytopenia associated with ARS.
authors.affiliation: Harbor Biosciences, 9171 Towne Centre Drive, San Diego, CA 92122, USA.
authors.forename: Dwight R
authors.initials: DR
authors.lastname: Stickney
authors.forename: Jessie R
authors.initials: JR
authors.lastname: Groothuis
authors.forename: Clarence
authors.initials: C
authors.lastname: Ahlem
authors.forename: Mike
authors.initials: M
authors.lastname: Kennedy
authors.forename: Barry S
authors.initials: BS
authors.lastname: Miller
authors.forename: Nanette
authors.initials: N
authors.lastname: Onizuka-Handa
authors.forename: Karen M
authors.initials: KM
authors.lastname: Schlangen
authors.forename: Daniel
authors.initials: D
authors.lastname: Destiche
authors.forename: Chris
authors.initials: C
authors.lastname: Reading
authors.forename: Armando
authors.initials: A
authors.lastname: Garsd
authors.forename: James M
authors.initials: JM
authors.lastname: Frincke
mesh_terms: D054508:Acute Radiation Syndrome / Q000188:drug therapy*; D000328:Adult; D000368:Aged; D015114:Androstenediol / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged
chemical_list: D015114:Androstenediol