scholarly journals SAT-LB16 Maintenance of Favorable Treatment Effect of Once-Weekly TransCon hGH for Children With Growth Hormone Deficiency: Interim Analysis From the Enlighten Long-Term Extension Trial

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Aristides K Maniatis ◽  
Samuel J Casella ◽  
Ulhas M Nadgir ◽  
Gail J Mick ◽  
Paul Hofman ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Treatment Effect ◽  
Interim Analysis ◽  
Hormone Deficiency ◽  
First Year ◽  
Treatment Naïve ◽  
Group A ◽  
Group B ◽  
Extension Trial

Abstract Background Once-weekly TransCon hGH is an investigational long-acting prodrug for growth hormone deficiency (GHD) that consists of 3 components: unmodified growth hormone (hGH; somatropin), an inert carrier that protects it, and a linker that temporarily binds the two. In the randomized phase 3 heiGHt Trial evaluating treatment-naïve children with GHD, TransCon hGH demonstrated superior annualized height velocity and ∆ height standard deviation score (SDS) compared to Genotropin and had a similar safety and tolerability profile. Methods Results are reported from an interim analysis of subjects from heiGHt who continued in the ongoing enliGHten long-term extension trial for 26 weeks. In the 52-week heiGHt Trial, treatment-naïve, prepubertal subjects with GHD were randomized 2:1 to receive once-weekly TransCon hGH 0.24 mg hGH/kg/week or an equivalent weekly dose of daily Genotropin. Subjects completing heiGHt could enroll in enliGHten, where all subjects received TransCon hGH. Two groups were analyzed: Group A (TransCon hGH in both heiGHt and enliGHten) and Group B (Genotropin in heiGHt, followed by TransCon hGH in enliGHten). Safety and growth outcomes were evaluated approximately every 13 weeks in heiGHt and enliGHten. IGF-1 was sampled on postdose Day 5 (±1 day) in enliGHten. A by-visit ANCOVA model was used to analyze numeric efficacy endpoints.ResultsAll but one subject who completed heiGHt continued into enliGHten (A: N=103, B: N=55). Baseline characteristics at the start of heiGHt were balanced between groups. The statistically significant treatment difference in ∆ height SDS (Group A vs B) at the end of heiGHt (Week 52, N=159; 1.10 vs 0.96, P=0.0149) was sustained through Week 78 (N=154; 1.39 vs 1.24, P=0.0436), demonstrating persistence of catch-up growth for both groups and maintenance of superior treatment effect for subjects treated with TransCon hGH in the first year of therapy. At Week 78, least-squares mean (SE) IGF-1 SDS on postdose Day 5 (N=153) was 0.52 (0.15) for Group A and 0.59 (0.19) for Group B. Adverse events (AEs) were comparable between groups during heiGHt. During enliGHten, 48.7% (76/156) and 1.9% (3/156) of subjects experienced AEs and serious AEs, respectively; the AE profile was consistent with what was previously observed in heiGHt. A low titer of anti-hGH binding antibodies were detected in 10/156 (6.4%) subjects during treatment with TransCon hGH in heiGHt and enliGHten; no neutralizing antibodies were detected. Lab parameters (HbA1c, cortisol, free thyroxine) were stable and generally remained within the normal range throughout the trials. Mean (SD) BMI SDS was 0.0 (0.8) for Group A and 0.1 (0.9) for Group B at Week 78.Conclusions Children treated with TransCon hGH showed continued improvement of height SDS beyond the first year. Treatment with TransCon hGH through 78 weeks demonstrated an AE and immunogenicity profile comparable to that of a daily hGH therapy.

scholarly journals Influence of biochemical diagnosis of growth hormone deficiency on replacement therapy response and retesting results at adult height

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Giulia Rodari ◽  
E. Profka ◽  
F. Giacchetti ◽  
I. Cavenaghi ◽  
M. Arosio ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Growth Hormone Deficiency ◽  
Adult Height ◽  
Initial Diagnosis ◽  
Stimulation Test ◽  
Hormone Deficiency ◽  
Group A ◽  
Group B ◽  
Term Response

AbstractIsolated growth hormone deficiency (IGHD) is the most frequent endocrinological disorder in children with short stature, however the diagnosis is still controversial due to the scarcity of reliable diagnostic criteria and pre-treatment predictive factors of long term-response. To evaluate recombinant growth hormone (rGH) long-term response and retesting results in three different groups of children divided in accordance with the biochemical criteria of initial diagnosis. Height gain (∆HT) at adult height (AH) and retesting results were evaluated in 57 rGH treated children (M = 34, 59.6%) divided into 3 groups according to initial diagnosis: Group A (n = 25) with max GH peak at stimulation test < 8 µg/L, Group B (n = 19) between 8 and 10 µg/L and Group C (n = 13) with mean overnight GH < 3 µg/L (neurosecretory dysfunction, NSD). Retesting was carried out in all patients after at least one month off therapy upon reaching the AH. 40/57 (70.2%) patients were pre-pubertal at diagnosis and showed ∆HT of 1.37 ± 1.00 SDS, with no significant differences between groups (P = 0.08). Nonetheless, 46% patients in Group B showed ∆HT < 1SDS (vs 13% and 12% in Group A and C, respectively) and 25% children failed to reach mid-parental height (vs 6% and 0% in Group A and C, respectively). At AH attainment, IGHD was reconfirmed in 28% (7/25) and 10% (2/19) in Group A and B, respectively. A reduction of diagnostic cut-off at GH stimulation tests could better discriminate between “good” and “poor responders” and predict the persistence of IGHD through transition. Group C response and the predictive value of baseline IGF-I SDS bring back to light NSD: should we consider an underlying hypothalamic derangement when the clinical presentation is strongly consistent with IGHD but pharmacological stimulation test is normal?

Transient impairment or delay of urinary trihydroxypregnanone (THS) response to metyrapone in boys with delayed adolescence and in patients with isolated growth hormone deficiency

1982 ◽  
Vol 99 (2) ◽  
pp. 166-173 ◽  
Author(s):  
M. Zachmann ◽  
D. Tassinari ◽  
W. Sorgo ◽  
G. U. Exner ◽  
B. Kempken ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Single Dose ◽  
Growth Hormone Deficiency ◽  
Bone Age ◽  
Urine Samples ◽  
Hormone Deficiency ◽  
Cortisol Response ◽  
Transient Impairment ◽  
Group A ◽  
Group B

Abstract. Twentythree boys with delayed adolescence (age 15.7 ± 2.0, bone age 12.4 ± 2.1 years) were studied. Their cortisol response to insulin was normal. After oral metyrapone (500 mg/m2 by mouth) one to three consecutive 12 h urine samples were collected for analysis of THS. Thirtyseven tests with 37 first, 21 second, and 11 third samples were carried out. The results could be divided into two main groups: 25 tests (group A) were subnormal in the first sample, 12 of them with a very weak (40 ± 8 μg/m2/12 h) and 13 with an insufficient (191 ± 16 μg/m2/12 h) THS response. Values in the second and third sample were higher, indicating a dealyed response. In 12 tests (group B), the results were normal (1016 ± 143 μg/m2/12 h) in the first and lower in the second and third samples. In three patients with repeated tests, there was improvement with increasing bone age. The THS-responses to metyrapone did not correlate with those of growth hormone, gonadotrophins, and TSH to stimuli. It is concluded that the THS-response to a single dose of metyrapone may be temporarily insufficient or delayed in delayed adolescence. We interpret this finding as showing transiently reduced or slow hypothalamic responsiveness.

scholarly journals Isolated Growth Hormone Deficiency and Idiopathic Short Stature: Comparative Efficiency after Growth Hormone Treatment up to Adult Height

2021 ◽  
Vol 10 (21) ◽  
pp. 4988
Author(s):  
Ana-Belen Ariza-Jimenez ◽  
Isabel Leiva Gea ◽  
Maria Jose Martinez-Aedo Ollero ◽  
Juan Pedro Lopez-Siguero
Keyword(s):  
Growth Hormone ◽  
Short Stature ◽  
Hormone Treatment ◽  
Treated Group ◽  
Idiopathic Short Stature ◽  
Hormone Deficiency ◽  
Comparative Efficiency ◽  
Height Gain ◽  
Group A ◽  
Group B

Introduction: Treatment with growth hormone (GH) is not approved for idiopathic short stature (ISS) in Europe. Objectives: To compare the growth of children treated with isolated GH deficiency (IGHD) vs. ISS-treated and untreated children. Methods: A retrospective descriptive study of patients treated in the last 14 years for IGHD (Group A), in comparison with ISS-treated (Group B) and untreated (Group C) subjects. Results: Group A had 67 males, who showed a height gain of 1.24 SD. Group B had 30 boys, who showed a height gain of 1.47 SD. Group C had 42 boys, who showed an improvement of 0.37 SD. The final heights were −1.52 SD, −1.31 SD, and −2.03 SD, respectively. Group A and C did not reach their target heights (with differences of 0.27 SD and 0.59 SD, respectively). Group B surpassed their target height by 0.29 SD. Conclusions: The final heights of the IGHD and treated ISS are similar. Treated groups were taller than untreated groups.

scholarly journals SAT-LB15 24-Month Efficacy and Safety of Once Weekly and Every Other Week Administration of GX-H9, Hybrid FC-Fused Long-Acting Human Growth Hormone: A Phase 2 Study in Children With Growth Hormone Deficiency

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Oleg Malievskiy ◽  
Aryaev Mykola ◽  
Nataliya Zelinska ◽  
Elena Bolshova ◽  
Ganna Senatorova ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Treatment Period ◽  
Study Drug ◽  
Hormone Deficiency ◽  
Height Velocity ◽  
First Year ◽  
Efficacy And Safety ◽  
Second Year ◽  
Long Acting

Abstract Objectives GX-H9 is a long-acting form of recombinant human GH under clinical development for both adults and children with GHD. In this report, 24-month efficacy and safety of once weekly and every other week (EOW) administration of GX-H9 were evaluated, in addition to Genotropin® switch-ability to GX-H9 after 12-month of treatment. Methods Subjects were randomly assigned to receive either one of three doses of GX-H9 (0.8 mg/kg/week, 1.2 mg/kg/week or 2.4 mg/kg every other week) or 0.03 mg/kg/day of Genotropin®. Treatment duration is 24-month for all patients in GX-H9 arms while patients in Genotropin® arm were re-randomized to one of three doses of GX-H9 at the completion of the first 12-month of treatment. Doses of GX-H9 were adjusted throughout the treatment period whenever necessary, based on IGF-1 levels. Results Out of 56 randomized, 54 received either GX-H9 or Genotropin®. Fifty subjects completed the 12-month treatment period. Of 50, 45 subjects completed the next 12-month, comprising 33 patients from GX-H9 and 12 patients who switched from Genotropin®. First year/second year mean±SD annualized height velocity (aHV) for 0.8 mg/kg/week, 1.2 mg/kg/week or 2.4 mg/kg every other week of GX-H9 were 10.50±2.54/9.14±1.96, 11.76±1.96/9.88±1.92 and 11.03±2.92/9.72±1.90 cm/year, respectively. First year mean±SD aHV for Genotropin® was 9.14±3.09 cm/year. Patients switched to one of the three doses of GX-H9 in the second year showed comparable aHV in the second year (8.73±2.69/7.60±0.90/9.13±1.07 cm/year for 0.8 mg/kg/week, 1.2 mg/kg/week and 2.4 mg/kg/EOW GX-H9, respectively). No significant slow-down of the growth was observed in the second year from patients who received GX-H9 throughout and patients who switched from Genotropin®. Mean change in height SDS after 12 months/24 months of GX-H9 treatment throughout from baseline treatment improved continuously (+1.10/+1.61 and +1.31/+1.89 and +1.15/+1.69 for 0.8 mg/kg/week, 1.2 mg/kg/week and 2.4 mg/kg EOW GX-H9, respectively). First year mean change in height SDS for Genotropin® was +0.92 SDS, and showed comparable improvement in height SDS after switching to GX-H9 weekly arms (+0.76 and +0.79 SDS for 0.8 mg/kg/week and 1.2 mg/kg/week, respectively). Most treatment-emergent adverse events were evaluated as unrelated to the study drug and were mild or moderate in severity. No new safety concerns were observed throughout 24 months of long-term GX-H9 treatment or after switching to GX-H9 from Genotropin®.Conclusions Growth response and safety profile of GX-H9 in children with GHD is comparable to those of daily GH, achieving robust growth rates after 24-month treatment. Subjects switched from Genotropin® in the second year, also showed substantial catch-up growth indicated by improvement in height SDS. GX-H9 has a unique potential to be a convenient long-term GH providing not only weekly but also twice-monthly treatment.

Long-term clinical results of the combination of cisplatin (C), vinblastine (V), DTIC (D) and interferon-alfa (I) with or without tamoxifen (T) for metastatic melanoma

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 8039-8039
Author(s):  
A. M. Sanguino ◽  
A. Y. Bedikian ◽  
S. S. Legha ◽  
M. A. Detry ◽  
N. E. Papadopoulos ◽  
...  
Keyword(s):  
Metastatic Melanoma ◽  
Interim Analysis ◽  
Response Rate ◽  
Complete Response ◽  
Clinical Results ◽  
Term Survival ◽  
Long Term Survival ◽  
Group A ◽  
Group B

8039 Background: According to 2001 AJCC data, 1-yr, 2-yr, 5-yr, and 10-yr survival of melanoma patients (pts) with stage M1c were 40.6%, 23.6%, 9.5% and 6.0%, respectively. Previously, we reported the interim results of a randomized phase II trial comparing the response rates (RR) of CVDI vs. CVDI +T. Here we report long-term survival results of these pts. Methods: Chemo-naïve pts between 16 and 75 yrs of age, with histologically documented diagnosis of advanced melanoma and without symptomatic brain metastasis, were randomized to receive either CVDI (group A) or CVDI+T (group B). The dose of each drug is as follows: C 15 mg/m2 IV (d 2–5), V 1.2 mg/m2 IV (d 1–5), D 600 mg/m2 IV (d 1), I 5 MU/m2 SQ 3 times a wk and T 20 mg twice a day. The treatment was administered every 3–4 wks. After the interim analysis, the arm with a higher RR was selected for an expansion cohort (group C). The primary endpoint was the RR of CVDI regimen with or without T. The secondary endpoint was overall survival (OS) evaluation. Results: A total of 104 pts were enrolled, among which 36 and 34 were randomized to group A and B, respectively. After interim analysis of 70 pts, the CVDI regimen was selected for group C. There were no significant differences in both RR (p= 0.126) and OS (p= 0.095) between group A and B. When all 104 pt data were combined, the overall response rate (ORR) was 37.5% with a complete response rate (CRR) of 8.7% and the median survival of 10.4 months. One-yr, 2-yr, 5-yr, and 10-yr OS were 43%, 20%, 7% and 4%, respectively. Conclusions: Although the combination of CVDI with or without T is an active regimen for treatment for metastatic melanoma, long-term survival of pts receiving this regimen is similar to historical controls. [Table: see text] No significant financial relationships to disclose.

scholarly journals Prevalence and clinical features of polycystic ovarian syndrome in adolescents with previous childhood growth hormone deficiency

2016 ◽  
Vol 29 (5) ◽  
Author(s):  
Alessandro Ciresi ◽  
Marco C. Amato ◽  
Jessica Bianco ◽  
Carla Giordano
Keyword(s):  
Growth Hormone ◽  
Polycystic Ovarian Syndrome ◽  
Ovarian Function ◽  
Hdl Cholesterol ◽  
Treated Group ◽  
Hormone Deficiency ◽  
Childhood Growth ◽  
Group A ◽  
Group B ◽  
Ovarian Syndrome

AbstractGrowth hormone (GH) plays a role in the regulation of ovarian function but there are limited data in women with GH deficiency (GHD). Our aim was to evaluate the features of polycystic ovarian syndrome (PCOS) in women with previous GHD.Data of 22 adolescents previously GH-treated (group A) were compared with those of 22 women with classical PCOS (group B) and 20 controls (group C).: Group A showed higher testosterone (p=0.048) and prevalence of menstrual irregularities (p<0.001) than group C. Compared to the group B, group A showed lower diastolic blood pressure (p=0.004), degree of hirsutism (p=0.005), testosterone (p=0.003) and prevalence of polycsytic ovaries (POC) morphology (p=0.024), with higher HDL-cholesterol (p=0.035) and 17-β-estradiol (p=0.009).: Adolescents with previous GHD show a higher prevalence of PCOS than controls, but with milder metabolic and hormonal features than adolescents with classical PCOS. A careful long-term follow-up is advisable in these patients.

scholarly journals Growth Hormone Treatment on Atherosclerosis: Results of a 5-Year Open, Prospective, Controlled Study in Male Patients with Severe Growth Hormone Deficiency

2008 ◽  
Vol 93 (9) ◽  
pp. 3416-3424 ◽  
Author(s):  
Annamaria Colao ◽  
Carolina Di Somma ◽  
Stefano Spiezia ◽  
Silvia Savastano ◽  
Francesca Rota ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Antihypertensive Drugs ◽  
Density Lipoprotein ◽  
Hormone Deficiency ◽  
Lipid Lowering ◽  
Controlled Study ◽  
Gh Replacement ◽  
Group A ◽  
Group B ◽  
Prospective Controlled Study

Background: Severe GH deficiency (GHD) is associated with, increased cardiovascular risk and intima-media thickness (IMT) at major arteries. Objective: The objective of the study was to investigate the 5-yr effects of GH replacement on common carotid IMT and insulin resistance syndrome (IRS) (at least two of the following: triglycerides levels ≥ 1.7 mmol/liter, high-density lipoprotein-cholesterol levels ≤ 1.0 mmol/liter, blood pressure above 130/85 mm Hg, fasting glucose 6.1–7 or 2 hr after glucose 7.7–11.1 mmol/liter). Design: This was an interventional, open, prospective, controlled study. Patients: Patients included 35 men with severe GHD and 35 age-matched healthy men as controls. Intervention: All patients received standard replacement therapy; GH replacement was added in 22 patients (group A) and refused by 13 others (group B). Measurements: Five-year changes in IMT and IRS prevalence were measured. Results: At baseline, IMT was higher in the patients with (P &lt; 0.001) and without IRS (P = 0.004) than in controls. Eighteen patients (51.4%) and two controls (5.7%; P &lt; 0.0001) had IRS. At study end, use of lipid-lowering drugs (92.3, vs. 13.6 and 34.3%, P &lt; 0.0001), glucose-lowering drugs (69.2 vs. 31.4 and 22.7%; P = 0.016), and antihypertensive drugs (61.5 vs. 20.0 and 4.5%; P &lt; 0.0001) was higher in group B patients than controls and group A patients. IGF-I levels normalized in all group A patients and remained lower than −1 sd score in 77% of group B patients. IMT significantly decreased only in group A and significantly increased in controls and nonsignificantly in group B patients. IRS prevalence significantly reduced only in group A patients. Conclusions: Severely hypopituitary GHD men have more frequently increased IMT at common carotid arteries and IRS than controls. After 5 years, only in GH replaced patients, IMT and prevalence of IRS decreased.

Comparative Study of effectiveness of mobilization with movement (MWM) and End range mobilization (ERM) techniques in frozen shoulder

2018 ◽  
Vol 4 (4) ◽  
pp. 519-522
Author(s):  
Jeyakumar S ◽  
Jagatheesan Alagesan ◽  
T.S. Muthukumar
Keyword(s):  
Range Of Motion ◽  
Frozen Shoulder ◽  
Type I ◽  
Mean Values ◽  
Functional Activities ◽  
Group A ◽  
The Mean ◽  
Group B

Background: Frozen shoulder is disorder of the connective tissue that limits the normal Range of motion of the shoulder in diabetes, frozen shoulder is thought to be caused by changes to the collagen in the shoulder joint as a result of long term Hypoglycemia. Mobilization is a therapeutic movement of the joint. The goal is to restore normal joint motion and rhythm. The use of mobilization with movement for peripheral joints was developed by mulligan. This technique combines a sustained application of manual technique “gliding” force to the joint with concurrent physiologic motion of joint, either actively or passively. This study aims to find out the effects of mobilization with movement and end range mobilization in frozen shoulder in Type I diabetics. Materials and Methods: 30 subjects both male and female, suffering with shoulder pain and clinically diagnosed with frozen shoulder was recruited for the study and divided into two groups with 15 patients each based on convenient sampling method. Group A patients received mobilization with movement and Group B patients received end range mobilization for three weeks. The outcome measurements were SPADI, Functional hand to back scale, abduction range of motion using goniometer and VAS. Results: The mean values of all parameters showed significant differences in group A as compared to group B in terms of decreased pain, increased abduction range and other outcome measures. Conclusion: Based on the results it has been concluded that treating the type 1 diabetic patient with frozen shoulder, mobilization with movement exercise shows better results than end range mobilization in reducing pain and increase functional activities and mobility in frozen shoulder.

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