Scp776, A Novel IGF-1 Fusion Protein for Acute Therapy to Promote Escape From Apoptosis in Tissues Affected by Ischemic Injury: 2 Randomized Placebo-Controlled Phase 1 Studies in Healthy Adults.

Abstract

Apoptosis is a major driver of cell loss and infarct expansion in ischemic injuries such as acute ischemic stroke (AIS) and acute myocardial infarction (AMI). Insulin-like growth factor-1 (IGF-1) can mitigate cell death and potentiate recovery following acute ischemic injury, but short half-life and nonspecificity limit its therapeutic potential. Scp776 is an IGF-1 fusion protein designed to target damaged tissue and promote apoptosis escape and is in clinical development as an acute therapy for AIS and AMI. Two phase 1 placebo-controlled studies in healthy volunteers evaluated safety, tolerability, pharmacokinetic profile, and pharmacodynamics under single (1, 2, or 4 mg/kg) or multiple (6, 6.2, or 7.25 mg/kg total doses) dosing regimens. In addition, a blood glucose management plan was developed and implemented to mitigate hypoglycemia that may develop following scp776 injection. Scp776 was well tolerated in healthy volunteers (n = 51) without serious adverse events. Exposure increased in a near dose-proportional manner with a mean half-life across all doses of 8 hours. Adaptive dextrose infusions maintained normal blood glucose levels with occasional mild hypoglycemic events. These results informed scp776 dose selection and the design of blood glucose monitoring protocols for phase 2 studies.