Background: ARG-007 is a cationic poly-arginine peptide consisting of 18 D-arginine residues developed by Argenica Therapeutics, with the goal of neuroprotection in ischaemic stroke and other neurological conditions. Pre-clinical studies with ARG-007 have demonstrated reduced infarct expansion compared with controls, no adverse effects in a model of intracerebral haemorrhage, and resistance to degradation by thrombolytic enzymes. Immunotoxicity studies showed no adverse immune responses. These data allowed for this first-in human study.
Aims:
1. Evaluate the safety and tolerability of escalating doses of ARG-007, by analysing incidence and severity of serious adverse (SAEs), adverse events (AEs), and clinically significant changes from baseline in clinical and laboratory parameters.
2. Determine the pharmacokinetic profile.
3. Assess immune reactivity.
Methods: Phase 1, double blind, randomised, placebo controlled trial in health adult volunteers. Four cohorts were randomly assigned to ARG-007 (0.03, 0.1, 0.2, and 0.3mg/kg) or placebo 3:1, administered by intravenous infusion over 10 minutes, then 48 hours of inpatient observation. The safety review committee reviewed safety data before proceeding to the next dose.
Results: 17 females, 15 males, mean age of 36.2 years participated. There were no SAEs. 13/24 (54.2%) subjects given ARG-007 reported at least one treatment emergent AE, compared to 5/8 (62.5%) given placebo; headache being the most common. AEs were not dose dependent.
Routine blood tests and vital signs showed no dose-related trend in changes over time.
Pharmacokinetic analysis revealed quantifiable seem levels from 5 minutes to 48 hours after the onset of the infusion, with a median half life of 12.4 to 15.8 hours. There were no notable trends in changes from baseline cytokine levels over time.
Conclusion: ARG-007 appears to be safe, have predictable pharmacokinetics, and no significant immunogenic response in healthy volunteers. A phase II study in large vessel occlusion stroke is planned.