Phase 1 study and population PK/PD modeling of long-acting growth hormone, GB08, to guide pediatric dosing

Area of Science:

• Endocrinology
• Pharmacology
• Biotechnology

Background:

• Growth hormone deficiency (GHD) treatment faces challenges with daily injections and adverse effects, impacting patient adherence.
• Novel therapies like GB08, a recombinant human growth hormone fused to an Fc fragment (Fc-GH), aim to reduce injection frequency and improve safety.
• Fc-fusion technology leverages extended half-life to potentially enhance treatment convenience.

Purpose of the Study:

• To evaluate the safety, immunogenicity, pharmacokinetics (PK), and pharmacodynamics (PD) of GB08 in healthy adults.
• To establish dosing strategies for a Phase 2 trial in pediatric GHD patients based on PK/PD modeling.
• To compare GB08's profile with existing GH therapies.

Main Methods:

• A randomized, double-blind, placebo-controlled single ascending dose trial was conducted.
• A randomized, open-label, parallel-group positive control trial compared GB08 to Jintrolong and Norditropin.
• Safety (adverse events), immunogenicity, PK, and PD were assessed following single doses of GB08 or positive controls.

Main Results:

• GB08 exhibited a favorable safety profile with mild to moderate adverse events and low immunogenicity.
• Pharmacokinetics and pharmacodynamics demonstrated dose-dependent effects, with a half-life of 81.7–110.0 hours, supporting weekly administration.
• Population PK/PD modeling identified an optimal adult dose of 0.7 mg/kg, with allometric scaling suggesting 0.8 mg/kg for pediatric GHD.

Conclusions:

• GB08 offers potential advantages over short-acting GH therapies, including improved treatment adherence and a potentially safer profile.
• The study provides crucial data to guide the dosing strategy for upcoming Phase 2 trials in pediatric GHD.
• GB08 represents a promising advancement in the long-term management of GHD.