Pharmacokinetic and pharmacodynamic profile of a new sustained-release GH formulation, LB03002, in children with GH deficiency

Abstract

Objective: LB03002 is a novel, sustained-release recombinant human GH, developed for once-a-week s.c. injection. To evaluate the suitability for long-term GH replacement therapy in children with GH deficiency (GHD), the present study assessed the pharmacokinetic (PK) and pharmacodynamic (PD) profiles of LB03002 at three doses. Study design and patients: The randomised, comparator-controlled, assessor-blinded, phase II study assessed 37 (24 boys, 13 girls) pre-pubertal, GH-naïve children with GHD, in 11 European centres, for PK and PD analyses. GH, IGF1 and IGFBP3 concentrations were measured following the last daily GH dose and the first and 13th once-a-week administration of LB03002 at doses of 0.2, 0.5 or 0.7 mg/kg. Results: GH C max values after the three doses of LB03002 were increased up to fourfold, with a clear dose proportionality. For each LB03002 dose, GH area under the concentration versus time curve did not increase from the first to 13th (month 3) administration, indicating no accumulation of circulating GH. IGF1 C max showed a progressive increase during LB03002 administration. Conversely, IGFBP3 showed a rapid increase in C max . IGF1 SDS were fully normalised after 3 months of treatment, whereas IGFBP3 SDS were already in the normal range for all the three LB03002 dosages after 1 week. Conclusions: At the doses used, LB03002 has a suitable profile for long-term treatment to promote growth in children with GHD. The quantitative changes in IGF1 and IGFBP3 indicate adequate stimulation of the IGF system by LB03002 and the pattern of increase is comparable with that seen in GHD children in a standard IGF1 generation test using daily GH.

Three-Year Efficacy and Safety of LB03002, a Once-Weekly Sustained-Release Growth Hormone (GH) Preparation, in Prepubertal Children with GH Deficiency (GHD)

“…The PK/PD profile of weekly injections of LB03002 in children with GHD was found to be comparable to that seen in adults, with elevated serum GH concentrations lasting up to 120 h and normalized IGF-I concentration after sc injections (8). The present report details the growth response to LB03002 administered once per week over a period of 3 yr, compared with daily GH injection, in a group of 51 prepubertal GH-naive children with a diagnosis of GHD.…”

“…Although the PK and PD properties of different formulations have been published (3)(4)(5)(6)(7)(8), clinical data on their use is still very limited and available only from relatively short-term studies performed either in children (9) or adults (10) with GHD. In children, only one study has evaluated the efficacy and safety of a depot GH preparation over the period of 1 yr (9).…”

Status of long-acting-growth hormone preparations — 2015

“…A 12-month follow-up in these patients showed that the changes in body composition were maintained [31]. In a phase 2 study of 37 prepubertal children, LB03002 given weekly in increasing doses of 0.2, 0.5 or 0.7 mg/kg showed a dose-related increase (normalization) in IGF-I levels [32]. Three years of GH therapy using LB03002 at doses of 0.5 and 0.7 mg/kg/week achieved similar growth as daily injections of GH (0.003 mg/kg/day).…”

Efficacy and safety of LB03002, a once-weekly sustained-release human GH for 12-month treatment in Korean children with GH deficiency

“…The pharmacokinetic and pharmacodynamic profile of LB03002 has been established in both children and adults with GH deficiency (GHD) (6,7). Preliminary efficacy and safety results from studies on GH-deficient children and adults have shown LB03002 to be a suitable candidate for long-term replacement therapy in patients with GHD (8,9).…”