First-in-man study with a novel PEGylated recombinant human insulin-like growth factor-I

Area of Science:

• Pharmacology
• Endocrinology
• Drug Development

Background:

• Insulin-like growth factor-I (IGF-I) is crucial for growth and metabolism.
• Unmodified recombinant human IGF-I (rhIGF-I) has limitations in therapeutic use.
• PEGylation is a strategy to improve drug pharmacokinetics.

Purpose of the Study:

• To assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of RO5046013 in humans.
• To compare RO5046013 with unmodified rhIGF-I.
• To evaluate the effects of PEGylated IGF-I on growth hormone (GH) secretion.

Main Methods:

• A single-center, randomized, double-blinded, placebo-controlled, single ascending dose study.
• 62 healthy volunteers received RO5046013 via subcutaneous injection or intravenous infusion.
• Safety, tolerability, pharmacokinetics, and pharmacodynamics were evaluated; rhIGF-I served as active comparator.

Main Results:

• RO5046013 demonstrated a prolonged half-life (140-200h) and dose-proportional exposure.
• The drug was safe and well-tolerated, with injection site erythema as the most common adverse event.
• RO5046013 caused minimal GH suppression compared to rhIGF-I, and no hypoglycemia occurred.

Conclusions:

• PEGylation of IGF-I significantly enhances its half-life.
• RO5046013 reduces negative GH feedback and hypoglycemia risk compared to rhIGF-I.
• PEGylated IGF-I presents a promising therapeutic alternative for relevant diseases.