Long-acting FC-fusion rhGH (GX-H9) shows potential for up to twice-monthly administration in GH-deficient adults

in European Journal of Endocrinology
Correspondence should be addressed to E J Lee; Email: ejlee423@yuhs.ac
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Objective

Hybrid Fc-fused rhGH (GX-H9) is a long-acting recombinant human growth hormone (GH) under clinical development for both adults and children with GH deficiency (GHD). We compared the safety, pharmacokinetics and pharmacodynamics of weekly and every other week (EOW) dosages of GX-H9 with those of daily GH administration in adult GHD (AGHD) patients.

Design

This was a randomized, open-label, active-controlled and dose-escalation study conducted in 16 endocrinology centers in Europe and Korea.

Methods

Forty-five AGHD patients with or without prior GH treatment were enrolled. Patients with prior GH treatments were required to have received the last GH administration at least 1 month prior to randomization. Subjects were sequentially assigned to treatment groups. Fifteen subjects were enrolled to each treatment group and randomly assigned to receive either GX-H9 or Genotropin (4:1 ratio). GX-H9 dosage regimens for Groups 1, 2 and 3 were 0.1 mg/kg weekly, 0.3 mg/kg EOW and 0.2 mg/kg EOW, respectively. All Genotropin-assigned subjects received 6 µg/kg Genotropin, regardless of treatment group. Main outcome analyses included measurements of serum insulin-like growth factor 1 (IGF-I), safety, pharmacokinetics, pharmacodynamics and immunogenicity.

Results

Mean GX-H9 peak and total exposure increased with an increase in dose after a single-dose administration. The mean IGF-I response was sustained above baseline over the intended dose interval of 168 h for the weekly and 336 h for the EOW GX-H9 groups. Safety profiles and immunogenicity were not different across the treatment groups and with Genotropin.

Conclusions

GX-H9 has the potential for up to twice-monthly administration.

Downloadable materials

  • Supplementary Figure 1
  • Supplementary Table 1 ANCOVA of lipid parameters (HDL-C, LDL-C, lipoprotein alpha, total cholesterol, and triglycerides), BMI, waist circumference, hip circumference, and waist to hip ratio at Week 12 (per-protocol set)
  • Supplementary Table 2 Summary of adverse events (safety set)

 

     European Society of Endocrinology

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Figures

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    Overall study design. Each group consisted of different subjects. After confirming an absence of safety issues, administration of GX-H9 at the applicable doses proceeded. EOW, every other week.

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    Serum concentrations of GX-H9 in the per-protocol set. The data are expressed as means ± standard deviations with linear and semilogarithmic scales. (A) A linear scale is shown, and (B) a semilogarithmic scale is shown.

  • View in gallery

    Changes in IGF-I and IGFBP-3 SDS in the per-protocol set. The data are expressed as means ± standard deviations with linear scales. (A) IGF-I SDS are shown, and (B) IGFBP-3 SDS are shown. Yellow boxes indicate a range of ±2 SDS. IFGBP-3, IGF-binding protein 3; IGF-I, insulin-like growth factor I; SDS, standard deviations.

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