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

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

Author information

1
National Children's Specialized Clinical Hospital, Kiev 04021, Ukraine.
2
University Hospital 'Sv. Marina', Varna 9010, Bulgaria.
3
St. Petersburg State Pediatric Medical Academy, St. Petersburg 194100, Russia.
4
Bashkir State Medical University, Ufa 450000, Russia.
5
Institute of Pediatric Endocrinology, Moscow 117036, Russia.
6
Russian Medical Academy of Postgraduate Education, Moscow 123995, Russia.
7
Oregon Health and Science University, Portland, Oregon 97239.
8
Kaplan Medical Center, Rehovot 7661041, Israel.
9
OPKO Biologics, Kiryat Gat 8211804, Israel.
10
2nd Children City Clinic, Minsk 220017, Belarus.

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.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT01592500.

PMID:
28323965
DOI:
10.1210/jc.2016-3547
[Indexed for MEDLINE]

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