Abstract

Background: Sustained-release GH formulations may provide a strategy for improving treatment compliance and persistence in GH-deficient patients. Objective: The aim of the study was to examine efficacy and safety of LB03002, a sustained-release GH formulation for once-weekly administration. Design: We conducted a phase III, 12-month, multinational, randomized, open-label, comparator-controlled trial with a 12-month uncontrolled extension. Patients: Prepubertal GH treatment-naive GH-deficient children (mean age, 7.8 y) participated in the study. Intervention: We administered once-weekly LB03002 (n = 91) or daily GH (n = 87) for 1 year, followed by once-weekly LB03002 for all patients for another year (LB03002 throughout, n = 87; switched to LB03002, n = 80). Outcome Measures: Height, height velocity (HV), IGF-1, GH antibodies, and adverse events were determined throughout. Primary analysis was noninferiority of LB03002 vs daily GH at 1 year by analysis of covariance. Results: Mean +/- SD HV during year 1 was 11.63 +/- 2.60 cm/y with LB03002, and 11.97 +/- 3.09 cm/y with daily GH, with increases from baseline of 8.94 +/- 2.91 and 9.04 +/- 3.19 cm/y, respectively. The least square mean HV difference for LB03002 - daily GH was -0.43 cm/y (99% confidence interval, -1.45 to 0.60 cm/y). Mean HV also remained above baseline in year 2 (8.33 +/- 1.92 cm/y in the LB03002 throughout group, and 7.28 +/- 2.34 cm/y in the switched to LB03002 group). Injection site reactions occurred more frequently in LB03002-treated patients but were considered mild to moderate in >90% of cases. Conclusions: Growth response with once-weekly LB03002 in GH-deficient children is comparable to that with daily GH, achieving expected growth rates for 24 months. Once-weekly LB03002 is a strong candidate for long-term GH replacement in GH-deficient children.