Long-Acting C-Terminal Peptide-Modified hGH (MOD-4023): Results of a Safety and Dose-Finding Study in GHD Children.
Daily injections are required for growth hormone (GH) replacement therapy, which may cause low compliance as a result of inconvenience and distress in patients.



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.



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).



The trial was conducted in 14 endocrinology centers in Europe.



Fifty-three prepubertal children with GHD completed 12 months of treatment with either MOD-4023 (N = 42) or r-hGH (N = 11).



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.



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.



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.
National Children's Specialized Clinical Hospital, Kiev 04021, Ukraine.
Nataliya
N
Zelinska
University Hospital 'Sv. Marina', Varna 9010, Bulgaria.
Violeta
V
Iotova
St. Petersburg State Pediatric Medical Academy, St. Petersburg 194100, Russia.
Julia
J
Skorodok
Bashkir State Medical University, Ufa 450000, Russia.
Oleg
O
Malievsky
Institute of Pediatric Endocrinology, Moscow 117036, Russia.
Valentina
V
Peterkova
Russian Medical Academy of Postgraduate Education, Moscow 123995, Russia.
Lubov
L
Samsonova
Oregon Health and Science University, Portland, Oregon 97239.
Ron G
RG
Rosenfeld
Kaplan Medical Center, Rehovot 7661041, Israel.
Zvi
Z
Zadik
OPKO Biologics, Kiryat Gat 8211804, Israel.
Michal
M
Jaron-Mendelson
OPKO Biologics, Kiryat Gat 8211804, Israel.
Ronit
R
Koren
OPKO Biologics, Kiryat Gat 8211804, Israel.
Leanne
L
Amitzi
2nd Children City Clinic, Minsk 220017, Belarus.
Dmitri
D
Raduk
OPKO Biologics, Kiryat Gat 8211804, Israel.
Oren
O
Hershkovitz
OPKO Biologics, Kiryat Gat 8211804, Israel.
Gili
G
Hart
D002648:Child; D002675:Child, Preschool; D003692:Delayed-Action Preparations; D004305:Dose-Response Relationship, Drug; D004393:Dwarfism, Pituitary / Q000188:drug therapy* / Q000378:metabolism; D005060:Europe; D005260:Female; D020249:Hormone Replacement Therapy; D019382:Human Growth Hormone / Q000008:administration & dosage*; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D011994:Recombinant Proteins
D003692:Delayed-Action Preparations; C515497:IGFBP3 protein, human; D018972:Insulin-Like Growth Factor Binding Protein 3; D011994:Recombinant Proteins; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I