Safety, Tolerability and Pharmacokinetics of the eNAMPT-Neutralizing ALT-100 Mab in Healthy Volunteers.

Abstract

Introduction: Human and preclinical studies have highlighted eNAMPT (extracellular nicotinamide phosphoribosyl transferase) as a druggable TLR4 ligand and DAMP involved in the pathobiology of diverse inflammatory, fibrotic and cancer disorders. This Phase 1 study assesses the safety, pharmacokinetics (PK) and pharmacodynamics (PD) of the humanized eNAMPT-neutralizing ALT-100 mAb as a strategy to address the unmet need for effective anti-inflammatory, anti-fibrotic therapeutics.

Materials and methods: Healthy male and female volunteers received a single intravenous ALT-100 dose (0.1, 0.4, 1.0, 4.0 mg/kg, n=24 dosed) or placebo (n=12 dosed) with 120-day monitoring (injection site, vital signs, hematology, coagulation, blood chemistry, urinalysis, PK/PD parameters, plasma biomarkers, anti-drug antibodies).

Results: ALT-100 was well tolerated at all doses without clinically significant changes in local tolerability, vital signs, or laboratory safety parameters. Treatment-emergent adverse events (TEAEs) were unrelated to ALT-100 mAb dose (mild/moderate in severity), and AEs were transient and resolved without clinical sequelae. There were no serious adverse events (SAEs). Median ALT-100 mAb plasma levels peaked at 0.62 hour after dosing (all doses). The mean maximum mAb plasma concentration (C_max) and mAb elimination half-life (T1/2) all increased in a dose-related manner between 0.4 mg/kg (17 days) and 4 mg/kg (27 days).

Conclusions: Single intravenous ALT-100 mAb doses are well tolerated in healthy participants with dose proportional PK and elimination half-life.