Two randomized, double-blind, placebo-controlled, dose-escalation phase 1 studies evaluating BTH1677, a 1, 3–1,6 beta glucan pathogen associated molecular pattern, in healthy volunteer subjects

• Published in: Investigational new drugs Vol. 34; no. 2; pp. 202 - 215
• Main Authors: Halstenson, C. E., Shamp, T., Gargano, M. A., Walsh, R. M., Patchen, M. L.
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.04.2016; Springer Nature B.V
• Subjects: Adolescent; Adult; Antibodies; Antigens; beta-Glucans - administration & dosage; beta-Glucans - adverse effects; beta-Glucans - pharmacokinetics; beta-Glucans - pharmacology; Cancer therapies; Clinical trials; Demography; Dose-Response Relationship, Drug; Double-Blind Method; Drug dosages; Electrocardiography; Female; Glucans - administration & dosage; Glucans - adverse effects; Glucans - pharmacokinetics; Glucans - pharmacology; Glucose; Healthy Volunteers; Hepatitis; Hormone replacement therapy; Humans; Immune system; Male; Medical laboratories; Medicine; Medicine & Public Health; Natural products; Oncology; Pathogen-Associated Molecular Pattern Molecules - administration & dosage; Pathogen-Associated Molecular Pattern Molecules - pharmacokinetics; Pathogen-Associated Molecular Pattern Molecules - pharmacology; Pathogens; Pharmaceutical sciences; Pharmaceuticals; Pharmacokinetics; Pharmacology/Toxicology; Phase I Studies; Placebos; Studies; Yeast; Young Adult; United States > US; BTH1677; Imprime PGG; Safety; Pharmacokinetics; Beta glucan; Pathogen associated molecular pattern
• ISSN: 0167-6997; 1573-0646
• DOI: 10.1007/s10637-016-0325-z

Summary Background BTH1677 is a beta glucan pathogen associated molecular pattern (PAMP) currently being investigated as a novel cancer therapy. Here, the initial safety and pharmacokinetic (PK) results of BTH1677 in healthy subjects are reported. Subjects and Methods In the Phase 1a single-dosing study, subjects were randomized (3:1 per cohort) to a single intravenous (iv) infusion of BTH1677 at 0.5, 1, 2, 4, or 6 mg/kg or placebo, respectively. In the Phase 1b multi-dosing study, subjects were randomized (3:1 per cohort) to 7 daily iv infusions of BTH1677 at 1, 2, or 4 mg/kg or placebo, respectively. Safety and PK non-compartmental analyses were performed. Results Thirty-six subjects ( N  = 24 Phase 1a; N  = 12 Phase 1b) were randomized to treatment. No deaths or serious adverse events occurred in either study. Mild or moderate adverse events (AEs) occurred in 67 % of BTH1677-treated subjects in both studies. Treatment-related AEs (occurring in ≥10 % of subjects) included dyspnea, flushing, headache, nausea, paraesthesia, and rash in Phase 1a and conjunctivitis and headache in Phase 1b. BTH1677 serum concentration was linear with dose. Clearance, serum elimination half-life (t 1/2 ) and volume of distribution (Vss) were BTH1677 dose-independent. In Phase 1b, area under the curve, t 1/2 , and Vss values were larger at steady state on days 6–30 versus day 0. Conclusions BTH1677 was well tolerated after single doses up to 6 mg/kg and after 7 daily doses up to 4 mg/kg.