Cheol Ryong Ku1, Thierry Brue2, Katharina Schilbach3, Stanislav Ignatenko4, Sandor Magony5, Yoon-Sok Chung6, Byung-Joon Kim7, Kyu Yeon Hur8, Ho-Cheol Kang9, Jung Hee Kim10, Min Seon Kim11, Aldona Kowalska12, Marek Bolanowski13, Marek Ruchala14, Svetozar Damjanovic15, Juraj Payer16, Yun Jung Choi17, Su Jin Heo17, Tae Kyoung Kim18, MinKyu Heo18, Joan Lee18, Eun Jig Lee1. 1. Endocrinology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea. 2. Aix-Marseille Université, INSERM U1251, Marseille Medical Genetics, and AP-HM, Hôpital Conception, Marseille, France. 3. Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Munich, Germany. 4. Charité Research Organisation, Berlin, Germany. 5. First Department of Medicine, University of Szeged, Szeged, Hungary. 6. Department of Endocrinology and Metabolism, Ajou University School of Medicine, Suwon, Republic of Korea. 7. Gachon University Gil Medical Center, Incheon, Republic of Korea. 8. Samsung Medical Center, Seoul, Republic of Korea. 9. Chonnam National University Hwasun Hospital, Hwasun-gun, Republic of Korea. 10. Seoul National University Hospital, Seoul, Republic of Korea. 11. Asan Medical Center, Seoul, Republic of Korea. 12. Endocrinology Clinic Holycross Cancer Centre, Swietokrzyskie, Poland. 13. Department of Endocrinology, Diabetes and Isotope Therapy, Wroclaw Medical University, Wroclaw, Poland. 14. Poznan University of Medical Sciences Chair and Department of Endocrinology, Metabolism and Internal Medicine, Poznań, Poland. 15. Clinical Center of Serbia, Belgrade, Serbia. 16. 5th Department of Internal Medicine, Comenius University Faculty of Medicine, University Hospital, Bratislava, Slovakia. 17. Handok Inc., Seoul, Republic of Korea. 18. Genexine Inc., Seongnam, Republic of Korea.
Abstract
OBJECTIVE:Hybrid Fc-fused rhGH (GX-H9) is a long-acting recombinant human growth hormone (GH) under clinical development for both adults and children with GH deficiency (GHD). We compared the safety, pharmacokinetics and pharmacodynamics of weekly and every other week (EOW) dosages of GX-H9 with those of daily GH administrationin adult GHD (AGHD) patients. DESIGN: This was a randomized, open-label, active-controlled and dose-escalation study conducted in 16 endocrinology centers in Europe and Korea. METHODS:Forty-five AGHD patients with or without prior GH treatment were enrolled. Patients with prior GH treatments were required to have received the last GH administration at least 1 month prior to randomization. Subjects were sequentially assigned to treatment groups. Fifteen subjects were enrolled to each treatment group and randomly assigned to receive either GX-H9 or Genotropin (4:1 ratio). GX-H9 dosage regimens for Groups 1, 2 and 3 were 0.1 mg/kg weekly, 0.3 mg/kg EOW and 0.2 mg/kg EOW, respectively. All Genotropin-assigned subjects received 6 µg/kg Genotropin, regardless of treatment group. Main outcome analyses included measurements of serum insulin-like growth factor 1 (IGF-I), safety, pharmacokinetics, pharmacodynamics and immunogenicity. RESULTS:Mean GX-H9 peak and total exposure increased with an increase in dose after a single-dose administration. The mean IGF-I response was sustained above baseline over the intended dose interval of 168 h for the weekly and 336 h for the EOW GX-H9 groups. Safety profiles and immunogenicity were not different across the treatment groups and with Genotropin. CONCLUSIONS: GX-H9 has the potential for up to twice-monthly administration.
RCT Entities:
OBJECTIVE: Hybrid Fc-fused rhGH (GX-H9) is a long-acting recombinant humangrowth hormone (GH) under clinical development for both adults and children with GH deficiency (GHD). We compared the safety, pharmacokinetics and pharmacodynamics of weekly and every other week (EOW) dosages of GX-H9 with those of daily GH administration in adult GHD (AGHD) patients. DESIGN: This was a randomized, open-label, active-controlled and dose-escalation study conducted in 16 endocrinology centers in Europe and Korea. METHODS: Forty-five AGHD patients with or without prior GH treatment were enrolled. Patients with prior GH treatments were required to have received the last GH administration at least 1 month prior to randomization. Subjects were sequentially assigned to treatment groups. Fifteen subjects were enrolled to each treatment group and randomly assigned to receive either GX-H9 or Genotropin (4:1 ratio). GX-H9 dosage regimens for Groups 1, 2 and 3 were 0.1 mg/kg weekly, 0.3 mg/kg EOW and 0.2 mg/kg EOW, respectively. All Genotropin-assigned subjects received 6 µg/kg Genotropin, regardless of treatment group. Main outcome analyses included measurements of serum insulin-like growth factor 1 (IGF-I), safety, pharmacokinetics, pharmacodynamics and immunogenicity. RESULTS: Mean GX-H9 peak and total exposure increased with an increase in dose after a single-dose administration. The mean IGF-I response was sustained above baseline over the intended dose interval of 168 h for the weekly and 336 h for the EOW GX-H9 groups. Safety profiles and immunogenicity were not different across the treatment groups and with Genotropin. CONCLUSIONS: GX-H9 has the potential for up to twice-monthly administration.
Authors: Kevin C J Yuen; Bradley S Miller; Cesar L Boguszewski; Andrew R Hoffman Journal: Front Endocrinol (Lausanne) Date: 2021-02-24 Impact factor: 5.555