Objective: Changes observed during adult GH deficiency (GHD) are most often reversed with the administration of recombinant human GH (rhGH). To avoid daily injections, a long-acting GH molecule has been obtained by covalent binding of polyethylene glycol (PEG) with rhGH (PEG-GH), allowing weekly s.c. injections. This study was designed to assess its efficacy and safety, in adult GHD subjects.
Design and methods: This was a randomized, double-blind, placebo-controlled, multiple-dose, parallel group study. Subjects were recruited from 34 centers. A total of 105 subjects with GHD were assigned a treatment. They received 6 weekly injections of either PEG-GH or placebo. Subjects were randomized into one out of four treatment groups (Groups A-D) or placebo (Group E). Groups A, B, and C received 1, 3, and 4 mg PEG-GH respectively, for the first 3 weeks followed by 2, 6, and 8 mg PEG-GH respectively, for the remaining 3 weeks. Group D received 4 mg PEG-GH for 6 weeks. Group E received placebo. The study was suspended because of the development of lipoatrophy in certain subjects and restarted with an injection rotation plan, before being terminated due to further subjects developing lipoatrophy.
Results: A total of 13 cases of injection-site lipoatrophy were reported, of which ten were in females and three occurred after the first injection; all cases were independent of PEG-GH dose or IGF1 levels, either basal or under treatment.
Conclusion: The unpredictable occurrence of injection-site lipoatrophy with weekly long-acting pegylated GH molecules may be a limiting factor for their development.
Trial registration: ClinicalTrials.gov NCT00308464.