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

Autor:	Strasburger CJ; Department of Medicine for EndocrinologyDiabetes and Nutritional Medicine, Charité Universitätsmedizin, Berlin, Germany., Vanuga P; Department of EndocrinologyNational Institute of Endocrinology and Diabetology, Lubochna, Slovakia., Payer J; Department of Internal Medicine VUniversity Hospital Ruzinov, Bratislava, Slovakia., Pfeifer M; Department of EndocrinologyUniversity Medical Centre Ljubljana, Ljubljana, Slovenia., Popovic V; Neuroendocrine UnitClinical Centre of Serbia, Belgrade, Serbia., Bajnok L; 1st Department of MedicineUniversity of Pécs, Pécs, Hungary., Góth M; 2nd Department of Internal MedicineMilitary Hospital - State Health Center, Budapest, Hungary., Olšovská V; II Internal Clinic in University Hospital St AnnaBrno, Czech Republic., Trejbalová L; I Department of Internal MedicineUniversity Hospital Bratislava, Bratislava, Slovakia., Vadasz J; 1st Department of Internal MedicineHetényi Géza Hospital and Out-Patient Clinic, Szolnok, Hungary., Fima E; OPKO BiologicsKiryat Gat, Israel., Koren R; OPKO BiologicsKiryat Gat, Israel., Amitzi L; OPKO BiologicsKiryat Gat, Israel., Bidlingmaier M; Medizinische Klinik - InnenstadtLudwig Maximilian University, Munich, Germany., Hershkovitz O; OPKO BiologicsKiryat Gat, Israel., Hart G; OPKO BiologicsKiryat Gat, Israel., Biller BMK; Neuroendocrine UnitMassachusetts General Hospital, Boston, Massachusetts, USA.
Jazyk:	angličtina
Zdroj:	European journal of endocrinology [Eur J Endocrinol] 2017 Mar; Vol. 176 (3), pp. 283-294. Date of Electronic Publication: 2016 Dec 08.
DOI:	10.1530/EJE-16-0748
Abstrakt:	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. (© 2017 The authors.)
Databáze:	MEDLINE
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