Long-Acting C-Terminal Peptide-Modified hGH (MOD-4023): Results of a Safety and Dose-Finding Study in GHD Children

J Clin Endocrinol Metab. 2017 May 1;102(5):1578-1587. doi: 10.1210/jc.2016-3547.


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.

Trial registration: ClinicalTrials.gov NCT01592500.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Child
  • Child, Preschool
  • Delayed-Action Preparations
  • Dose-Response Relationship, Drug
  • Dwarfism, Pituitary / drug therapy*
  • Dwarfism, Pituitary / metabolism
  • Europe
  • Female
  • Hormone Replacement Therapy
  • Human Growth Hormone / administration & dosage*
  • Humans
  • Insulin-Like Growth Factor Binding Protein 3 / metabolism
  • Insulin-Like Growth Factor I / metabolism
  • Male
  • Recombinant Proteins


  • Delayed-Action Preparations
  • IGFBP3 protein, human
  • Insulin-Like Growth Factor Binding Protein 3
  • Recombinant Proteins
  • Human Growth Hormone
  • Insulin-Like Growth Factor I

Associated data

  • ClinicalTrials.gov/NCT01592500