Nataliya Zelinska1, Violeta Iotova2, Julia Skorodok3, Oleg Malievsky4, Valentina Peterkova5, Lubov Samsonova6, Ron G Rosenfeld7, Zvi Zadik8, Michal Jaron-Mendelson9, Ronit Koren9, Leanne Amitzi9, Dmitri Raduk10, Oren Hershkovitz9, Gili Hart9. 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 eitherMOD-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.
RCT Entities:
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 humanGH (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 humanGH (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.
Authors: Dennis M Fisher; Ron G Rosenfeld; Michal Jaron-Mendelson; Leanne Amitzi; Ronit Koren; Gili Hart Journal: Horm Res Paediatr Date: 2017-04-11 Impact factor: 2.852