Long-Acting C-Terminal Peptide-Modified hGH (MOD-4023): Results of a safety and dose-finding study in Ghd children

Nataliya Zelinska, Violeta Iotova, Julia Skorodok, Oleg Malievsky, Valentina Peterkova, Lubov Samsonova, Ronald (Ron) Rosenfeld, Zvi Zadik, Michal Jaron-Mendelson, Ronit Koren, Leanne Amitzi, Dmitri Raduk, Oren Hershkovitz, Gili Hart

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Context: Daily injections are required for growth hormone (GH) replacement therapy, which may cause low compliance as a result of inconvenience and distress in patients. Objective: C-terminal peptide-modified human GH (MOD-4023) is developed for once-a-week dosing regimen in GH-deficient (GHD) adults and children. The present trial was a safety and dose-finding study for weekly MOD-4023 in GHD children. Design: A multicenter, open-label, randomized, controlled phase 2 study in children with GHD, evaluating the safety, tolerability, pharmacokinetics/pharmacodynamics, and efficacy of three different weekly MOD-4023 doses, compared with daily recombinant human GH (r-hGH). Setting: The trial was conducted in 14 endocrinology centers in Europe. Patients: Fifty-three prepubertal children with GHD completed 12 months of treatment with either MOD-4023 (N = 42) or r-hGH (N = 11). Interventions: C-terminal peptide-modified hGH (MOD-4023) was administered weekly at a dose of either 0.25, 0.48, or 0.66 mg/kg/wk and compared with daily hGH at a dose of 0.24 mg/kg/wk. Results: MOD-4023 showed an estimated half-life approximately fivefold to 10-fold longer when compared with daily r-hGH. Insulin-like growth factor (IGF)-I and IGF-binding peptide 3 showed a dose-dependent increase during MOD-4023 treatment. IGF-I standard deviation score for MOD-4023 did not exceed +2. All MOD-4023 cohorts demonstrated adequate catch-up growth. The 0.66 mg/kg/wk dose demonstrated efficacy closest to daily r-hGH. No serious adverse events were observed during MOD-4023 treatment, and its tolerability was consistent with known properties of r-hGH. Conclusions: This study confirms the long-acting properties of MOD-4023 and shows a promising safety and tolerability profile. This provides support for initiation of a phase 3 study in GHD children using a single weekly injection of MOD-4023. (J Clin Endocrinol Metab 102: 1578-1587, 2017).

Original languageEnglish (US)
Pages (from-to)1578-1587
Number of pages10
JournalJournal of Clinical Endocrinology and Metabolism
Volume102
Issue number5
DOIs
StatePublished - May 1 2017

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

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    Zelinska, N., Iotova, V., Skorodok, J., Malievsky, O., Peterkova, V., Samsonova, L., Rosenfeld, R. R., Zadik, Z., Jaron-Mendelson, M., Koren, R., Amitzi, L., Raduk, D., Hershkovitz, O., & Hart, G. (2017). Long-Acting C-Terminal Peptide-Modified hGH (MOD-4023): Results of a safety and dose-finding study in Ghd children. Journal of Clinical Endocrinology and Metabolism, 102(5), 1578-1587. https://doi.org/10.1210/jc.2016-3547