A long‐acting pegylated recombinant human growth hormone (Jintrolong ® ) in healthy adult subjects: Two single‐dose trials evaluating safety, tolerability and pharmacokinetics

2018 ◽  
Vol 43 (5) ◽  
pp. 640-646 ◽  
Author(s):  
Y. Guan ◽  
F. He ◽  
J. Wu ◽  
L. Zhao ◽  
X. Wang ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Single Dose ◽  
Human Growth Hormone ◽  
Healthy Adult ◽  
Recombinant Human Growth Hormone ◽  
Human Growth ◽  
Long Acting

scholarly journals Reduced Effectiveness and Comparable Safety in Biweekly vs. Weekly PEGylated Recombinant Human Growth Hormone for Children With Growth Hormone Deficiency: A Phase IV Non-Inferiority Threshold Targeted Trial

2021 ◽  
Vol 12 ◽  
Author(s):  
Chengjun Sun ◽  
Biao Lu ◽  
Yu Liu ◽  
Yaqin Zhang ◽  
Haiyan Wei ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Growth Hormone Deficiency ◽  
Human Growth Hormone ◽  
Recombinant Human Growth Hormone ◽  
Human Growth ◽  
Hormone Deficiency ◽  
Height Velocity ◽  
Clinical Trial Registration ◽  
Long Acting ◽  
Phase Iv

ContextLong-acting recombinant human growth hormone (rhGH) has transformed growth hormone deficiency (GHD) treatment. However, the possibility and rationality for flexible time regimen are pending.ObjectiveWe studied the efficacy of biweekly versus weekly PEGylated rhGH (PEG-rhGH) therapy in GHD children.Design, Setting, and PatientsThis multicenter, phase IV trial with a non-inferiority threshold ≥20% enrolled 585 Tanner stage I GHD children.InterventionSubjects randomly received 0.20 mg/kg once-weekly or biweekly PEG-rhGH, or 0.25 mg/kg.w rhGH once daily for 26 weeks.Main Outcome MeasureThe primary outcome was height SD scores for chronological age (HtSDSCA) at week 26 and safety measurements including adverse events (AEs), IGF-2, and IGFBP-2 changes.ResultsAt week 26, the median HtSDSCA changed from −2.75, −2.82, and −2.78 to −2.31, −2.43, and −2.28 with weekly and biweekly PEG-rhGH, and daily rhGH, respectively. The difference in HtSDSCA was 0.17 ± 0.28 between weekly and biweekly PEG-rhGH, and 0.17 ± 0.27 between daily rhGH and biweekly PEG-rhGH, failing the non-inferiority threshold. Nevertheless, the height velocity of children receiving biweekly PEG-rhGH reached 76.42%–90.34% and 76.08%–90.60% that of children receiving weekly PEG-rhGH and daily rhGH, respectively. The rate of AEs was comparable among the groups. No statistical difference was observed in IGF-2 and IGFBP-2 levels among the groups. IGFBP-2 levels decreased over time in all groups, with no notable difference in IGF-2 and IGFBP-2 changes among the three treatment groups.ConclusionsAlthough notably promoted height velocity, biweekly PEG-rhGH failed the non-inferiority threshold as compared with either weekly PEG-rhGH or daily rhGH. Compared with short-term rhGH, long-acting PEG-rhGH did not significantly increase tumor-associated IGF-2 and IGFBP-2 expressions.Clinical Trial Registrationclinicaltrials.gov, identifier NCT02976675.

scholarly journals Stimulation of monocyte chemotaxis by human growth hormone and its deactivation by somatostatin

Blood ◽  
1993 ◽  
Vol 82 (3) ◽  
pp. 954-960 ◽  
Author(s):  
CJ Wiedermann ◽  
N Reinisch ◽  
H Braunsteiner
Keyword(s):  
Growth Hormone ◽  
Human Growth Hormone ◽  
Recombinant Human Growth Hormone ◽  
Human Growth ◽  
Inhibitory Effect ◽  
Boyden Chamber ◽  
Recombinant Growth Hormone ◽  
Monocyte Chemotaxis ◽  
Long Acting

Monocyte infiltration occurs early in the course of inflammation and is a prerequisite for optimal repair of tissue damage. In this study, human recombinant growth hormone was shown to be a potent chemoattractant for human monocytes, inducing migration at picomolar concentrations of recombinant human growth hormone. Chemotaxis of monocytes was measured in vitro by a modified Boyden chamber assay using nitrocellulose micropore filters and measuring microscopically the migration depth of the leading front of monocytes. Somatostatin, which inhibits the release of growth hormone, and its long-acting analogue, octreotide, also stimulated chemotaxis of monocytes; however, the effective peptide concentration was in the micromolar range. When tested for chemotaxis in combination or in experiments using pretreatment with somatostatin and washing of treated cells, somatostatin significantly antagonized the chemotactic responses of monocytes to growth hormone. The inhibitory effect on growth hormone- stimulated chemotaxis was dose dependent and occurred at concentrations severalfold lower than the chemotactically active concentration of somatostatin. Combinations of growth hormone with interferon or substance P also deactivated the chemotactic responses. These observations suggest that human growth hormone may have a regulatory role in monocyte chemotaxis.

scholarly journals A Cell-Based Strategy for Bioactivity Determination of Long-Acting Fc-Fusion Recombinant Human Growth Hormone

Molecules ◽  
2019 ◽  
Vol 24 (7) ◽  
pp. 1389 ◽  
Author(s):  
Wenrong Yao ◽  
Lei Yu ◽  
Wenhong Fan ◽  
Xinchang Shi ◽  
Lan Liu ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Human Growth Hormone ◽  
Recombinant Human Growth Hormone ◽  
Accurate Determination ◽  
Human Growth ◽  
Luciferase Reporter ◽  
Promising Alternative ◽  
A Cell ◽  
Long Acting

The long-acting growth hormone (LAGH) is a promising alternative biopharmaceutical to treat growth hormone (GH) deficiency in children, and it was developed using a variety of technologies by several pharmaceutical companies. Most LAGH preparations, such as Fc fusion protein, are currently undergoing preclinical study and clinical trials. Accurate determination of bioactivity is critical for the efficacy of quality control systems of LAGH. The current in vivo rat weight gain assays used to determine the bioactivity of recombinant human GH (rhGH) in pharmacopoeias are time-consuming, expensive, and imprecise, and there are no recommended bioassays for LAGH bioactivity in pharmacopoeias. Therefore, we developed a cell-based bioassay for bioactivity determination of therapeutic long-acting Fc-fusion recombinant human growth hormone (rhGH-Fc) based on the luciferase reporter gene system, which is involved in the full-length human GH receptor (hGHR) and the SG (SIE and GAS) response element. The established bioassay was comprehensively validated according to the International Council for Harmonization (ICH) Q2 (R1) guidelines and the Chinese Pharmacopoeia, and is highly precise, time-saving, simple, and robust. The validated bioassay could be qualified for bioactivity determination during the research, development, and manufacture of rhGH-Fc, and other LAGH formulations.

scholarly journals Stimulation of monocyte chemotaxis by human growth hormone and its deactivation by somatostatin

Blood ◽  
1993 ◽  
Vol 82 (3) ◽  
pp. 954-960 ◽  
Author(s):  
CJ Wiedermann ◽  
N Reinisch ◽  
H Braunsteiner
Keyword(s):  
Growth Hormone ◽  
Human Growth Hormone ◽  
Recombinant Human Growth Hormone ◽  
Human Growth ◽  
Inhibitory Effect ◽  
Boyden Chamber ◽  
Recombinant Growth Hormone ◽  
Monocyte Chemotaxis ◽  
Long Acting

Abstract Monocyte infiltration occurs early in the course of inflammation and is a prerequisite for optimal repair of tissue damage. In this study, human recombinant growth hormone was shown to be a potent chemoattractant for human monocytes, inducing migration at picomolar concentrations of recombinant human growth hormone. Chemotaxis of monocytes was measured in vitro by a modified Boyden chamber assay using nitrocellulose micropore filters and measuring microscopically the migration depth of the leading front of monocytes. Somatostatin, which inhibits the release of growth hormone, and its long-acting analogue, octreotide, also stimulated chemotaxis of monocytes; however, the effective peptide concentration was in the micromolar range. When tested for chemotaxis in combination or in experiments using pretreatment with somatostatin and washing of treated cells, somatostatin significantly antagonized the chemotactic responses of monocytes to growth hormone. The inhibitory effect on growth hormone- stimulated chemotaxis was dose dependent and occurred at concentrations severalfold lower than the chemotactically active concentration of somatostatin. Combinations of growth hormone with interferon or substance P also deactivated the chemotactic responses. These observations suggest that human growth hormone may have a regulatory role in monocyte chemotaxis.

scholarly journals Use of PEGylated Recombinant Human Growth Hormone in Chinese Children with Growth Hormone Deficiency: A 24-Month Follow-Up Study

2019 ◽  
Vol 2019 ◽  
pp. 1-7
Author(s):  
Yu Qiao ◽  
Zengmin Wang ◽  
Jinyan Han ◽  
Guimei Li
Keyword(s):  
Growth Hormone ◽  
Human Growth Hormone ◽  
Pediatric Patients ◽  
Recombinant Human Growth Hormone ◽  
Human Growth ◽  
Bone Age ◽  
Hormone Deficiency ◽  
Height Velocity ◽  
Rhgh Therapy ◽  
Long Acting

Objective. Once-weekly PEGylated recombinant human growth hormone (rhGH) is the sole long-acting GH formulation available currently for pediatric patients with GH deficiency (GHD). The aim of this study was to evaluate the efficacy and safety of PEGylated rhGH therapy compared to daily rhGH therapy in GHD children treated for two years. Methods. A total of 98 children (49 children for the PEGylated rhGH group and 49 children for the daily rhGH group) with GHD were enrolled in this single-center, prospective, nonrandomized cohort study. PEGylated rhGH or daily rhGH was administered for 2 years. Height, height SDS, height velocity (HV), IGF-1, bone age (BA), and adverse events were determined throughout the treatment. Results. HV significantly increased over the baseline and was similar in both groups. In the PEGylated rhGH cohort, the mean ± SD HV was improved from 3.78 ± 0.78 cm/y at the baseline to 12.44 ± 3.80 cm/y at month 3, to 11.50 ± 3.01 cm/y at month 6, to 11.00 ± 2.32 cm/y at month 12, and finally 10.08 ± 2.12 cm/y at month 24 in the PEGylated rhGH group. In the daily rhGH group, HV was 3.36 ± 1.00 cm/y at baseline, increasing to 12.56 ± 3.71 cm/y at month 3, to 11.82 ± 2.63 cm/y at month 6, to 10.46 ± 1.78 cm/y at month 12, and to 9.28 ± 1.22 cm/y at month 24. No serious adverse event related to PEGylated rhGH or daily rhGH occurred during the 24-month study. Conclusion. PEGylated rhGH replacement therapy is effective and safe in pediatric patients with GHD. The adherence to once-weekly PEGylated rhGH therapy is superior to daily rhGH in children with GHD.

Sign in / Sign up

Export Citation Format

Share Document