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Eur J Endocrinol. 2017 Mar;176(3):283-294. doi: 10.1530/EJE-16-0748. Epub 2016 Dec 8.

MOD-4023, a long-acting carboxy-terminal peptide-modified human growth hormone: results of a Phase 2 study in growth hormone-deficient adults.

Author information

1
Department of Medicine for EndocrinologyDiabetes and Nutritional Medicine, Charité Universitätsmedizin, Berlin, Germany.
2
Department of EndocrinologyNational Institute of Endocrinology and Diabetology, Lubochna, Slovakia.
3
Department of Internal Medicine VUniversity Hospital Ruzinov, Bratislava, Slovakia.
4
Department of EndocrinologyUniversity Medical Centre Ljubljana, Ljubljana, Slovenia.
5
Neuroendocrine UnitClinical Centre of Serbia, Belgrade, Serbia.
6
1st Department of MedicineUniversity of Pécs, Pécs, Hungary.
7
2nd Department of Internal MedicineMilitary Hospital - State Health Center, Budapest, Hungary.
8
II Internal Clinic in University Hospital St AnnaBrno, Czech Republic.
9
I Department of Internal MedicineUniversity Hospital Bratislava, Bratislava, Slovakia.
10
1st Department of Internal MedicineHetényi Géza Hospital and Out-Patient Clinic, Szolnok, Hungary.
11
OPKO BiologicsKiryat Gat, Israel.
12
Medizinische Klinik - InnenstadtLudwig Maximilian University, Munich, Germany.
13
OPKO BiologicsKiryat Gat, Israel ghart@opko.com.
14
Neuroendocrine UnitMassachusetts General Hospital, Boston, Massachusetts, USA.

Abstract

OBJECTIVE:

Growth hormone (GH) replacement therapy currently requires daily injections, which may cause distress and low compliance. C-terminal peptide (CTP)-modified growth hormone (MOD-4023) is being developed as a once-weekly dosing regimen in patients with GH deficiency (GHD). This study's objective is to evaluate the safety, pharmacokinetics (PK), pharmacodynamics (PD) and efficacy of MOD-4023 administered once-weekly in GHD adults.

DESIGN:

54 adults with GHD currently treated with daily GH were normalized and randomized into 4 weekly dosing cohorts of MOD-4023 at 18.5%, 37%, 55.5% or 123.4% of individual cumulative weekly molar hGH dose. The study included 2 stages: Stage A assessed the effectiveness and PK/PD profiles of the 4 dosing regimens of MOD-4023. Stage B was an extension period of once-weekly MOD-4023 administration (61.7% molar hGH content) to collect further safety data and confirm the results from Stage A.

RESULTS:

Dose-dependent response was observed for both PK and PD data of weekly MOD-4023 treatment. Insulin-like growth factor I (IGF-I) SDS levels were maintained within normal range. The 18.5% cohort was discontinued due to low efficacy. MOD-4023 was well tolerated and exhibited favorable safety profile in all dose cohorts. The reported adverse events were consistent with known GH-related side effects.

CONCLUSIONS:

Once-weekly MOD-4023 administration in GHD adults was found to be clinically effective while maintaining a favorable safety profile and may obviate the need for daily injections. Weekly GH injections may improve compliance and overall outcome. The promising results achieved in this Phase 2 study led to a pivotal Phase 3 trial, which is currently ongoing.

Comment in

PMID:
27932411
PMCID:
PMC5292974
DOI:
10.1530/EJE-16-0748
[Indexed for MEDLINE]
Free PMC Article

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