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

7 Citations (Scopus)

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

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Human Growth Hormone
Insulin-Like Growth Factor I
Safety
Peptides
Growth Hormone
Endocrinology
Pharmacodynamics
Pharmacokinetics
Somatomedins
Labels
Injections
Hormone Replacement Therapy
Compliance
Half-Life
Therapeutics
Growth

ASJC Scopus subject areas

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

Cite this

Long-Acting C-Terminal Peptide-Modified hGH (MOD-4023) : Results of a safety and dose-finding study in Ghd children. / Zelinska, Nataliya; Iotova, Violeta; Skorodok, Julia; Malievsky, Oleg; Peterkova, Valentina; Samsonova, Lubov; Rosenfeld, Ronald (Ron); Zadik, Zvi; Jaron-Mendelson, Michal; Koren, Ronit; Amitzi, Leanne; Raduk, Dmitri; Hershkovitz, Oren; Hart, Gili.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 102, No. 5, 01.05.2017, p. 1578-1587.

Research output: Contribution to journalArticle

Zelinska, N, Iotova, V, Skorodok, J, Malievsky, O, Peterkova, V, Samsonova, L, Rosenfeld, RR, 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, vol. 102, no. 5, pp. 1578-1587. https://doi.org/10.1210/jc.2016-3547
Zelinska, Nataliya ; Iotova, Violeta ; Skorodok, Julia ; Malievsky, Oleg ; Peterkova, Valentina ; Samsonova, Lubov ; Rosenfeld, Ronald (Ron) ; Zadik, Zvi ; Jaron-Mendelson, Michal ; Koren, Ronit ; Amitzi, Leanne ; Raduk, Dmitri ; Hershkovitz, Oren ; Hart, Gili. / Long-Acting C-Terminal Peptide-Modified hGH (MOD-4023) : Results of a safety and dose-finding study in Ghd children. In: Journal of Clinical Endocrinology and Metabolism. 2017 ; Vol. 102, No. 5. pp. 1578-1587.
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T2 - Results of a safety and dose-finding study in Ghd children

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AU - Skorodok, Julia

AU - Malievsky, Oleg

AU - Peterkova, Valentina

AU - Samsonova, Lubov

AU - Rosenfeld, Ronald (Ron)

AU - Zadik, Zvi

AU - Jaron-Mendelson, Michal

AU - Koren, Ronit

AU - Amitzi, Leanne

AU - Raduk, Dmitri

AU - Hershkovitz, Oren

AU - Hart, Gili

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N2 - 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).

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