scholarly journals Effective GH replacement with once-weekly somapacitan vs daily GH in children with GHD: 3-year results from REAL 3

2021 ◽  
Author(s):  
Lars Sävendahl ◽  
Tadej Battelino ◽  
Michael Højby Rasmussen ◽  
Meryl Brod ◽  
Paul Saenger ◽  
...  
Keyword(s):  
Gh Deficiency ◽  
Standard Deviation Score ◽  
Height Velocity ◽  
First Year ◽  
Gh Therapy ◽  
Once Daily ◽  
Randomized Controlled ◽  
Phase 2 Study ◽  
Igf I ◽  
Long Acting

Abstract Context Current GH therapy requires daily injections, which can be burdensome. Somapacitan is a long-acting GH derivative in development for treatment of GH deficiency (GHD). Objective Evaluate the efficacy, safety, and tolerability of once-weekly somapacitan after 3 years of treatment. Design A multicenter, randomized, controlled, phase 2 study comparing somapacitan and once-daily GH for 156 weeks (NCT02616562). Setting Twenty-nine sites in 11 countries. Patients Fifty-nine children with GHD randomized (1:1:1:1) and exposed to treatment. Fifty-three children completed the 3-year period. Interventions Patients received somapacitan (0.04 [n=14], 0.08 [n=15] or 0.16 [n=14] mg/kg/week) or daily GH (n=14) (0.034 mg/kg/day, equivalent to 0.238 mg/kg/week) subcutaneously during the first year, after which all patients on somapacitan received 0.16 mg/kg/week. Main Outcome Measures Height velocity (HV) at year 3; changes from baseline in height standard deviation score (HSDS), HVSDS and IGF-I SDS. Results The estimated treatment difference (95% CI) in HV for somapacitan 0.16/0.16 mg/kg/week versus daily GH at year 3 was 0.8 cm/year (−0.4; 2.1). Change in HVSDS from baseline to year 3 was comparable between somapacitan 0.16/0.16 mg/kg/week, the pooled somapacitan groups, and daily GH. A gradual increase in HSDS from baseline was observed for all groups. At year 3, mean HSDS was similar for the pooled somapacitan groups and daily GH. Change from baseline to year 3 in mean IGF-I SDS was similar across treatments. Conclusions Once-weekly somapacitan in children with GHD showed sustained efficacy over 3 years in all assessed height-based outcomes with similar safety and tolerability to daily GH.

scholarly journals Safety and convenience of once-weekly somapacitan in adult GH deficiency: a 26-week randomized, controlled trial

2018 ◽  
Vol 178 (5) ◽  
pp. 491-499 ◽  
Author(s):  
Gudmundur Johannsson ◽  
Ulla Feldt-Rasmussen ◽  
Ida Holme Håkonsson ◽  
Henrik Biering ◽  
Patrice Rodien ◽  
...  
Keyword(s):  
Injection Site ◽  
Treatment Satisfaction ◽  
Gh Deficiency ◽  
Standard Deviation Score ◽  
Fixed Dose ◽  
Once Daily ◽  
Randomized Controlled ◽  
Injection Site Reactions ◽  
Adult Gh Deficiency ◽  
Igf I

Objective Somapacitan is a reversible albumin-binding growth hormone (GH) derivative, developed for once-weekly administration. This study aimed to evaluate the safety of once-weekly somapacitan vs once-daily Norditropin®. Local tolerability and treatment satisfaction were also assessed. Design 26-week randomized, controlled phase 3 safety and tolerability trial in six countries (Nbib2382939). Methods Male or female patients aged 18–79 years with adult GH deficiency (AGHD), treated with once-daily GH for ≥6 months, were randomized to once-weekly somapacitan (n = 61) or once-daily Norditropin (n = 31) administered subcutaneously by pen. Both treatments were dose titrated for 8 weeks to achieve insulin-like growth factor I (IGF-I) standard deviation score (SDS) levels within the normal range, and then administered at a fixed dose. Outcome measures were adverse events (AEs), including injection site reactions; occurrence of anti-somapacitan/anti-GH antibodies and change in treatment satisfaction, assessed using the Treatment Satisfaction Questionnaire for Medication-9 (TSQM-9). Results Mean IGF-I SDS remained between 0 and 2 SDS throughout the trial in both groups. AEs were mostly mild or moderate and transient in nature. The most common AEs were nasopharyngitis, headache and fatigue in both groups. More than 1500 somapacitan injections were administered and no clinically significant injection site reactions were reported. No anti-somapacitan or anti-GH antibodies were detected. The TSQM-9 score for convenience increased significantly more with somapacitan vs Norditropin (P = 0.0171). Conclusions In this 26-week trial in patients with AGHD, somapacitan was well tolerated and no safety issues were identified. Once-weekly somapacitan was reported to be more convenient than once-daily Norditropin.

scholarly journals Significance of Direct Confirmation of Growth Hormone Insensitivity for the Diagnosis of Primary IGF-I Deficiency

2020 ◽  
Vol 9 (1) ◽  
pp. 240
Author(s):  
Joanna Smyczyńska ◽  
Urszula Smyczyńska ◽  
Maciej Hilczer ◽  
Renata Stawerska ◽  
Andrzej Lewiński
Keyword(s):  
Growth Hormone ◽  
Final Height ◽  
Standard Deviation Score ◽  
Height Velocity ◽  
Gh Therapy ◽  
Significant Difference ◽  
Igf I ◽  
Growth Hormone Insensitivity ◽  
Stimulation Tests ◽  
Direct Confirmation

Primary insulin-like growth factor-I (IGF-I) deficiency is a synonym of growth hormone (GH) insensitivity (GHI), however the necessity of direct confirmation of GH resistance by IGF-I generation test (IGF-GT) is discussed. GHI may disturb intrauterine growth, nevertheless short children born small for gestational age (SGA) are treated with GH. We tested the hypothesis that children with appropriate birth size (AGA), height standard deviation score (SDS) <−3.0, GH peak in stimulation tests (stimGH) ≥10.0 µg/L, IGF-I <2.5 centile, and excluded GHI may benefit during GH therapy. The analysis comprised 21 AGA children compared with 6 SGA and 20 GH-deficient ones, with height SDS and IGF-I as in the studied group. All patients were treated with GH up to final height (FH). Height velocity, IGF-I, and IGF binding protein-3 (IGFBP-3) concentrations before and during first year of treatment were assessed. Effectiveness of therapy was better in GHD than in IGF-I deficiency (IGFD), with no significant difference between SGA and AGA groups. All but two AGA children responded well to GH. Pretreatment IGF-I and increase of height velocity (HV) during therapy but not the result of IGF-GT correlated with FH. As most AGA children with apparent severe IGFD benefit during GH therapy, direct confirmation of GHI seems necessary to diagnose true primary IGFD in them.

Growth Hormone Therapy in Children with Kabuki Syndrome: 1-year Treatment Results

2017 ◽  
Vol 88 (3-4) ◽  
pp. 258-264 ◽  
Author(s):  
Dina A. Schott ◽  
Willem J.M. Gerver ◽  
Constance T.R.M. Stumpel
Keyword(s):  
Growth Hormone ◽  
Gh Deficiency ◽  
Standard Deviation Score ◽  
Height Velocity ◽  
Kabuki Syndrome ◽  
Body Proportions ◽  
Leg Length ◽  
Gh Treatment ◽  
Igf I ◽  
Rhgh Treatment

Background/Aims: Kabuki syndrome (KS) is a rare genetic malformation syndrome, resulting in characteristic features such as short stature. We investigate whether growth hormone (GH) treatment increases linear height and influences body proportions in KS children. Methods: In this prospective study, 18 genetically confirmed prepubertal KS children (9 females and 9 males) aged from 3.8 to 10.1 years (mean 6.8 ± 2.1 years) were treated with recombinant human GH (rhGH) for 1 year. Calculations for height, height velocity, BMI, sitting height, and subischial leg length were made. Bone age, insulin-like growth factor (IGF-I), and IGF binding protein 3 (IGFBP-3) were also measured. Results: This study showed an increase in height standard deviation score (SDS) for the whole group from –2.40 to –1.69 (p < 0.05) after 1 year of rhGH treatment. The change in height SDS within 1 year was >0.7 SDS for 10 subjects and >0.5 SDS for 3 subjects. The mean IGF-I SDS at the start of the study was –0.70 (±1.07), which increased after 12 months to 1.41 (±0.91) (p < 0.05). KS children who received rhGH at a younger age displayed significantly greater increases in height than those who started when they were older. The same was true for both gene mutation KMT2D versus KDM6A and for GH deficiency versus non-GH deficiency KS children (p < 0.05). Throughout the course of rhGH treatment, the subjects’ body proportions remained normal. Conclusions: All participants experienced catch-up growth during the year of rhGH treatment, but without an influence on body proportions.

scholarly journals Corroboration of Height Velocity Prediction Markers for rhGH with an Oral GH Secretagogue Treatment in Children with GHD

2021 ◽  
Author(s):  
Werner F Blum ◽  
George M Bright ◽  
Minh-Ha T Do ◽  
John C McKew ◽  
Haiying Chen ◽  
...  
Keyword(s):  
Recombinant Human Growth Hormone ◽  
Standard Deviation Score ◽  
Human Growth ◽  
Height Velocity ◽  
First Year ◽  
Growth Responses ◽  
Baseline Serum ◽  
Igf I ◽  
Treatment Data ◽  
Rhgh Treatment

Abstract Context Recombinant human growth hormone (rhGH) is approved for treatment of pediatric GH deficiency (PGHD), with greatest growth responses observed in those with severe GHD. Orally administered GH secretagogues (GHS) may be useful treatment in patients with moderate GHD. Distinguishing children with severe vs. moderate GHD could identify children who would be better treated with rhGH or GHS. Objectives Evaluate baseline insulin-like growth factor-I (IGF-I) and stimulated peak GH response as predictors of 12-month height velocity (HV) in children with GHD. Design Data on children with GHD were analyzed in a legacy data base (GeNeSIS data). Participants 514 naïve to rhGH-treatment, prepubertal children with idiopathic isolated GHD (IGHD) for whom stimulated GH, baseline serum IGF-I and first year HV during rhGH treatment data are available. Outcome Measures Children with severe or moderate GHD were categorized based on GH and IGF-I data and evaluated based on baseline auxologic and hormone profiles and first year growth response to rhGH. Results Cohorts of severe and moderate GHD were 81/514 (15.8%) and 433/514 (84.2%). Cohorts differed significantly with regard to indicators of GHD (e.g., baseline height standard deviation score [SDS], height SDS minus target height SDS, HV, HV SDS, and change in height SDS during rhGH treatment). Multiple regression analysis showed IGF-I and stimulated GH were significant predictors of HV independent of other known variables. Expected first year HV in moderate GHD was 8.3 cm/year. Conclusions The combination of peak GH to GH stimulation testing and baseline IGF-I concentration are predictive enrichment markers for annualized HV responses to rhGH therapy.

scholarly journals Comparison between the growth response to growth hormone (GH) therapy in children with partial GH insensitivity or mild GH deficiency

2014 ◽  
Vol 58 (1) ◽  
pp. 23-29 ◽  
Author(s):  
Daniela F. Cardoso ◽  
Carlos Eduardo Martinelli Jr. ◽  
Viviane C. Campos ◽  
Elenilde S. Gomes ◽  
Ívina E. S. Rocha ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Gh Deficiency ◽  
Care Service ◽  
Standard Deviation Score ◽  
Laboratory Data ◽  
First Year ◽  
Gh Therapy ◽  
Public Care ◽  
Initial Height ◽  
One Year

Objectives: GH therapy is still controversial, except in severe GH deficiency (SGHD). The objective of this study was to compare the response to growth hormone (GH) therapy in children with partial GH insensitivity (PGHIS) and mild GH deficiency (MGHD) with those with SGHD.Subjects and methods: Fifteen PGHIS, 11 MGHD, and 19 SGHD subjects, followed up for more than one year in the Brazilian public care service, were evaluated regarding anthropometric and laboratory data at the beginning of treatment, after one year (1 st year) on treatment, and at the last assessment (up to ten years in SGHD, up to four years in MGHD, and up to eight years in PGHIS).Results: Initial height standard deviation score (SDS) in SGHD was lower than in MGHD and PGHIS. Although the increase in 1 st year height SDS in comparison to initial height SDS was not different among the groups, height-SDS after the first year of treatment remained lower in SGHD than in MGHD. There was no difference in height-SDS at the last assessment of the children among the three groups. GH therapy, in the entire period of observation, caused a trend towards lower increase in height SDS in PGHIS than SGHD but similar increases were observed in MGHD and SGHD.Conclusion: GH therapy increases height in PGHIS and produces similar height effects in MGHD and SGHD.

Growth hormone deficiency in 'little' mice results in aberrant body composition, reduced insulin-like growth factor-I and insulin-like growth factor-binding protein-3 (IGFBP-3), but does not affect IGFBP-2, -1 or -4

1993 ◽  
Vol 136 (1) ◽  
pp. 91-104 ◽  
Author(s):  
L. R. Donahue ◽  
W. G. Beamer
Keyword(s):  
Body Composition ◽  
Growth Factor ◽  
Gh Deficiency ◽  
Body Water ◽  
Insulin Like Growth Factor ◽  
Gh Therapy ◽  
Factor I ◽  
Igf I ◽  
Body Compartments ◽  
Igfbp 3

ABSTRACT Although GH is known to regulate somatic growth during development, its role in regulating adult body composition is less well defined. The effects of GH on individual body compartments – water, fat, protein and mineral – are achieved both by the action of GH and by a GH-induced hormone, insulin-like growth factor-I (IGF-I). We used a genetic model of GH deficiency, the 'little' (gene symbol lit) mouse, to determine the GH regulation of IGF-I and its insulin-like growth factor-binding proteins (IGFBPs) and to define the interaction between these hormones and each body compartment in adults. Our results showed that GH-deficient lit/lit mice had reduced levels of serum IGF-I (range 38–130 μg/l) compared with normal lit/+ littermates (range 432–567 μg/l) between 2 and 52 weeks of age. The lit/lit mice did not experience the fivefold increase in IGF-I between 2 and 4 weeks of age that was seen in lit/+ mice. In lit/lit serum, overall binding of 125I-labelled IGF-I to the four IGFBPs was reduced, solely in response to a reduced amount of IGFBP-3. No overall differences were found between lit/lit and lit/+ mice in the binding of 125I-labelled IGF-I to IGFBP-2, -1 or -4. Age-related declines in IGF-I and IGFBPs were seen in lit/lit mice. However, adult levels of IGF-I were maintained in lit/+ mice to at least 52 weeks of age, as were levels of IGFBP-1 and -4, while IGFBP-3 and -2 declined with age. With respect to body composition, comparison of lit/lit with lit/+ mice showed that the lit/lit mice were characterized by abnormally large adipose tissue stores and reduced body water, protein and mineral from 2 weeks onward. These changes occurred despite normal energy intake in lit/lit mice up to 52 weeks of age, indicating that neither undernutrition nor hyperphagia is characteristic of this GH-induced model of obesity. Furthermore, lit/lit males accrued more body fat beginning at an earlier age than lit/lit females. With advancing age, the per cent body fat increased in both lit/lit and lit/+ mice, while the per cent body water and mineral declined. In lit/lit but not lit/+ mice, per cent protein also declined with age. The changes in body water and fat are attributable to lack of adequate GH in the genetically GH-deficient lit/lit mouse. On the other hand, the changes in body protein are more likely to be effects of IGF-I. Changes in mineral observed in lit/lit mice could be the result of action by GH, IGF-I or both hormones. Therefore, when GH is chronically manipulated by GH deficiency as in lit/lit mice, by GH excess as in acromegaly, or by GH therapy, all four body compartments are affected, suggesting that GH therapy is most valuable when the treatment goal is to alter overall body composition. Journal of Endocrinology (1993) 136, 91–104

scholarly journals A Randomized Phase 2 Study of Long-Acting TransCon GH vs Daily GH in Childhood GH Deficiency

2017 ◽  
Vol 102 (5) ◽  
pp. 1673-1682 ◽  
Author(s):  
Pierre Chatelain ◽  
Oleg Malievskiy ◽  
Klaudziya Radziuk ◽  
Ganna Senatorova ◽  
Magdy O. Abdou ◽  
...  
Keyword(s):  
Adverse Events ◽  
Gh Deficiency ◽  
Area Under The Curve ◽  
Study Drug ◽  
Height Velocity ◽  
Controlled Study ◽  
Open Label ◽  
Safety And Efficacy ◽  
Treatment Naïve ◽  
Long Acting

Abstract Context: TransCon Growth Hormone (GH) (Ascendis Pharma) is a long-acting recombinant sustained-release human GH prodrug in development for children with GH deficiency (GHD). Objective: To compare the pharmacokinetics, pharmacodynamics, safety, and efficacy of weekly TransCon GH to that of daily GH in prepubertal children with GHD. Design: Randomized, open-label, active-controlled study of three doses of weekly TransCon GH versus daily Genotropin (Pfizer). Setting: Thirty-eight centers in 14 European countries and Egypt. Patients: Prepubertal male and female treatment-naïve children with GHD (n = 53). Interventions: Subjects received one of three TransCon GH doses (0.14, 0.21, or 0.30 mg GH/kg/wk) or Genotropin 0.03 mg GH/kg/d for 26 weeks. Main Outcome Measures: GH and insulinlike growth factor-1 (IGF-1) levels, growth, adverse events, and immunogenicity. Results: Both GH maximum concentration and area under the curve were similar following TransCon GH or Genotropin administration at comparable doses. A dose response was observed, with IGF-1 standard deviation scores increasing into the normal range for all three TransCon GH doses. Annualized mean height velocity for the three TransCon GH doses ranged from 11.9 cm to 13.9 cm, which was not statistically different from 11.6 cm for Genotropin. Adverse events were mild to moderate, and most were unrelated to the study drug. Injection site tolerance was good. One TransCon GH subject developed a low-titer, nonneutralizing antibody response to GH. Conclusions: The results suggest that long-acting TransCon GH is comparable to daily Genotropin for GH (pharmacokinetics) and IGF-1 (pharmacodynamics) levels, safety, and efficacy and support advancement into phase 3 development.

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