scholarly journals Design of the ForesiGHt Trial: A Multicenter, Randomized, Placebo- and Active-Controlled Trial to Compare Once-Weekly TransCon hGH (lonapegsomatropin) to Placebo and Daily Somatropin in Adults With Growth Hormone Deficiency (GHD)

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A519-A520
Author(s):  
Maria Fleseriu ◽  
Jens Otto Jorgensen ◽  
Kevin C J Yuen ◽  
Charlotte Hoybye ◽  
Meng Mao ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Fat Mass ◽  
Lean Mass ◽  
Shielding Effect ◽  
Fixed Dose ◽  
Dose Titration ◽  
Phase 3 ◽  
Gh Replacement ◽  
Patient Reported ◽  
Total Body

Abstract BackgroundAdult GHD results from insufficient growth hormone (GH) secretion from the anterior pituitary gland and may represent either a continuation of childhood-onset GHD or GHD acquired during adulthood. Clinically, adult GHD is associated with central adiposity, decreased lean muscle mass, increased fat mass, decreased bone mineral density, and reduced quality of life. Current standard of care consists of GH replacement via daily injections. Lonapegsomatropin is a long-acting prodrug of somatropin (hGH), designed to deliver unmodified hGH with a weekly exposure profile. Lonapegsomatropin consists of somatropin that is transiently bound to a carrier via a proprietary TransCon Linker. The carrier extends the duration of somatropin in the circulation through a shielding effect that minimizes renal excretion and receptor-mediated clearance of the prodrug. At physiologic conditions, lonapegsomatropin releases fully active, unmodified somatropin via autocleavage of the linker in a controlled manner. The safety and efficacy of lonapegsomatropin have previously been evaluated in two phase 3 trials and one long-term extension trial in pediatric GHD. Changes in body composition are an objective and sensitive endpoint that reflects biologic activity of GH and clinical efficacy of GH replacement. Methods: The primary objective of the foresiGHt trial is to evaluate the efficacy of once-weekly lonapegsomatropin compared to placebo at 38 weeks in adults with GHD. The trial will be conducted at approximately 120 sites in North America, Europe, Asia, and Oceania. Approximately 240 subjects will be randomized 1:1:1 to once-weekly lonapegsomatropin, once-weekly placebo, or daily somatropin (Norditropin®). Subjects will be treatment-naïve or without GH therapy for at least 12 months. Subjects with well-controlled non-insulin dependent diabetes mellitus (HbA1c ≤ 7.5%) will be eligible. Following screening, the 38-week treatment period will consist of a 12-week gradual dose titration period and 26 weeks of fixed dose maintenance. Fixed dosing will be used to ensure maximal comparability across the treatment arms in the trial. Three dosing groups per arm will be established to allow for differences in age and oral estrogen intake in women. The primary endpoint is change from baseline in trunk percent fat at week 38, as measured by dual energy X-ray absorptiometry (DXA). Secondary efficacy endpoints are change from baseline in trunk fat mass and change in total body lean mass at week 38. Exploratory efficacy endpoints include total body fat mass, trunk lean mass, visceral adipose tissue, and patient-reported outcomes. Conclusion: The ongoing global phase 3 foresiGHt trial is designed to assess the efficacy, safety, and tolerability of lonapegsomatropin by weekly administration, compared to weekly placebo and daily hGH replacement therapy in adults with GHD.

scholarly journals Examining Bone, Muscle and Fat in Middle-Aged Long-Term Endurance Runners: A Cross-Sectional Study

2020 ◽  
Vol 9 (2) ◽  
pp. 522
Author(s):  
Ulrike H. Mitchell ◽  
Bruce Bailey ◽  
Patrick J. Owen
Keyword(s):  
Exercise Training ◽  
Aerobic Exercise ◽  
Fat Mass ◽  
Lean Mass ◽  
Aerobic Exercise Training ◽  
Middle Aged ◽  
Cross Sectional ◽  
Endurance Runners ◽  
Total Body

Aerobic exercise training has many known cardiovascular benefits that may promote healthy aging. It is not known if long-term aerobic exercise training is also associated with structural benefits (e.g., lower fat mass, higher areal bone mineral density (BMD) and greater muscle mass). We evaluated these parameters in middle-aged long-term endurance runners compared to sex-, age-, height-, and weight-matched non-running controls. Total and regional lean and fat mass and areal BMD were assessed by dual-energy X-ray absorptiometry. Sagittal magnetic resonance images captured the cross-sectional area and thickness of the lumbar multifidus. Runners (n = 10; all male) had a mean (standard deviation; SD) age of 49 (4) years, height of 178.9 (4.9) cm, weight of 67.8 (5.8) kg, body mass index (BMI) of 21.4 (1.4) kg/m2 and had been running 82.6 (27.9) km/week for 23 (13) years. Controls (n = 9) had a mean (SD) age of 51 (5) years, height of 176.0 (5.1) cm, weight of 72.8 (7.1) kg, and BMI of 23.7 (2.1) kg/m2. BMI was greater in controls (p = 0.010). When compared to controls on average, runners had a 10 percentage-point greater total body lean mass than controls (p = 0.001) and 14% greater trunk lean mass (p = 0.010), as well as less total body (8.6 kg; p < 0.001), arm (58%; p = 0.002), leg (52%; p < 0.001), trunk (73%; p < 0.001), android (91%; p < 0.001), and gynoid fat mass (64%; p < 0.001). No differences were observed between groups for BMD outcomes or multifidus size. These results underscore the benefits of endurance running to body composition that carry over to middle-age.

scholarly journals Healthcare utilization, quality of life and patient-reported outcomes during two years of GH replacement therapy in GH-deficient adults – comparison between Sweden, The Netherlands and Germany

2006 ◽  
Vol 154 (6) ◽  
pp. 843-850 ◽  
Author(s):  
Bernhard Saller ◽  
Anders F Mattsson ◽  
Peter H Kann ◽  
Hans P Koppeschaar ◽  
Johan Svensson ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Growth Hormone ◽  
Replacement Therapy ◽  
Healthcare Utilization ◽  
Patient Reported Outcomes ◽  
Gh Deficiency ◽  
European Countries ◽  
Gh Replacement ◽  
Patient Reported

Objective: This study set out to determine the change in quality of life (QoL) and healthcare utilization during 2 years of growth hormone (GH) replacement therapy in adults with GH deficiency. Data were compared from three European countries. Design: Analysis was made from KIMS, the Pfizer International Metabolic Database on adult GH deficiency. Methods: QoL and healthcare utilization were measured at baseline and after 1 and 2 years of GH replacement in patient cohorts from Sweden (n = 302), The Netherlands (n = 103) and Germany (n = 98). QoL was assessed by the QoL-Assessment in Growth Hormone Deficient Adults (QoL-AGHDA) questionnaire, and the KIMS Patient Life Situation Form was used to evaluate healthcare utilization. Results: QoL improved significantly (P < 0.0001) and comparably in all three cohorts. The improvement was seen during the first year of treatment and QoL remained improved during the second year. The number of days in hospital was reduced by 83% (P < 0.0001) during GH replacement. There were no country-specific differences either at baseline or during follow-up. The same was true for the number of days of sick leave (reduction of 63%; P = 0.0004). Significant reductions were recorded in the number of doctor visits in each of the three cohorts after 2 years of GH replacement (P < 0.05). Conclusions: This study provides a detailed comparative analysis of GH replacement therapy in GHD patients in three European countries. Despite some differences in treatment strategies, the beneficial effects on QoL, patient-reported outcomes and healthcare utilization are essentially similar in the healthcare environment of Western European countries.

scholarly journals Osteoarthritis of the Distal Interphalangeal and First Carpometacarpal Joints is Associated with High Bone Mass in Women and Small Bone Size and Low Lean Mass in Men

2015 ◽  
Vol 9 (1) ◽  
pp. 399-404 ◽  
Author(s):  
Thord von Schewelov ◽  
Håkan Magnusson ◽  
Maria Cöster ◽  
Caroline Karlsson ◽  
Björn E Rosengren
Keyword(s):  
Lean Body Mass ◽  
Body Mass ◽  
Fat Mass ◽  
Lean Mass ◽  
Bone Size ◽  
Hand Osteoarthritis ◽  
Mineral Density ◽  
High Bone Mass ◽  
Carpometacarpal Joints ◽  
Total Body

Objective: To determine if primary hand osteoarthritis (OA) is associated with abnormal bone and anthropometric traits. Methods: We used DXA to measure total body bone mineral density (BMD), femoral neck width (bone size) and total body lean and fat mass in 39 subjects with hand OA (primary DIP and/or CMC I) and 164 controls. Data are presented as mean Z-scores or Odds Ratios (OR) with 95% confidence intervals. Results: Women with hand OA had (compared to controls) higher BMD (0.5(0.1,0.9)) but similar bone size (-0.3(-0.8,0.2)), lean mass (0.3(-0.3,0.9)), fat mass (-0.1(-0.6,0.5)) and BMI (0.0(-0.6,0.6)). Men with hand OA had (compared to controls) similar BMD (-0.1(-0.7,0.6)), smaller bone size (-0.5(-1.1,-0.01)), lower lean mass (-0.6(-1.1,-0.04)), and similar fat mass (-0.2(-0.7,0.4)) and BMI -0.1(-0.6,0.6). In women, each SD higher BMD was associated with an OR of 1.8 (1.03, 3.3) for having hand OA. In men each SD smaller bone size was associated with an OR of 1.8 (1.02, 3.1) and each SD lower proportion of lean body mass with an OR of 1.9 (1.1, 3.3) for having hand OA. Conclusion: Women with primary DIP finger joint and/or CMC I joint OA have a phenotype with higher BMD while men with the disease have a smaller bone size and lower lean body mass.

scholarly journals Perception of Treatment Burden With Once Weekly Somatrogon vs Once Daily Genotropin in Pediatric Patients With Growth Hormone Deficiency (GHD): Results From a Randomized Phase 3 Study

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A680-A681
Author(s):  
Aristides K Maniatis ◽  
Mauri Carakushansky ◽  
Sonya Galcheva ◽  
Gnanagurudasan Prakasam ◽  
Larry A Fox ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Treatment Period ◽  
Pediatric Patients ◽  
Recombinant Human Growth Hormone ◽  
Daily Injection ◽  
Treatment Burden ◽  
Phase 3 ◽  
Once Daily ◽  
Treatment Experience ◽  
Patient Reported

Abstract Background: Somatrogon is a long-acting recombinant human growth hormone (rhGH) comprised of the amino acid sequence of hGH and 3 copies of the carboxy-terminal peptide from human chorionic gonadotropin. Somatrogon is being developed as a once weekly subcutaneous (SC) injectable treatment for pediatric patients (pts) with GHD. Aims: To evaluate patient and caregiver perceptions of the treatment burden associated with a once weekly somatrogon SC injection schedule compared with a once daily Genotropin SC injection schedule. Methods: In this phase 3 (NCT03831880), open-label, crossover study, pediatric pts (3 to &lt;18 years) with GHD on at least 3 months stable rhGH therapy were randomized 1:1 to receive treatment according to 1 of 2 sequences: Sequence #1, 12 weeks of Genotropin once daily followed by 12 weeks of somatrogon once weekly; Sequence #2, 12 weeks of somatrogon once weekly followed by 12 weeks of Genotropin once daily. The primary objective of the study was to evaluate treatment burden assessed as the difference between mean overall Life Interference (LI) total scores after each 12-week treatment period of weekly somatrogon and daily Genotropin. Secondary objectives further assessed treatment experience of pts and caregivers after each treatment period and their comparison of both treatments at the end of the study. A recently developed, validated dyad questionnaire (Turner-Bowker DM et al, 2020) was administered as an electronic Patient Reported Outcome to collect all assessments. Results: Eighty-seven pts were randomized to Sequence #1 (n=43) or Sequence #2 (n=44) with 85 pts completing the study. Somatrogon administered as a once weekly injection had a lower (statistically significant) treatment burden than Genotropin administered as a once daily injection, based on the mean overall LI total scores after somatrogon (8.63) vs Genotropin (24.13) treatment (mean difference: -15.49; two-sided 95% CI: [-19.71, -11.27]; P &lt;0.0001). Compared with once daily Genotropin, once weekly somatrogon was associated with greater convenience, higher satisfaction with treatment experience, and less life interference for the caregiver. A higher proportion of pts preferred once weekly somatrogon and demonstrated a greater intent to comply with treatment. The proportion of pts who experienced at least one treatment-emergent adverse event (TEAE) with Genotropin and somatrogon treatment were 44.2% and 54.0%, respectively. Injection site pain was the most common TEAE during the Genotropin (12.8%) and somatrogon (14.9%) treatment periods and was rated as mild in most cases. No severe or serious adverse events were reported. Conclusions: In pediatric pts with GHD, compared with Genotropin administered once daily, somatrogon administered once weekly has a lower treatment burden as shown by less life interference, and is associated with a more favorable treatment experience.

Anamorelin in patients with advanced non-small cell lung cancer and cachexia: Results from the phase III studies ROMANA 1 and 2.

2015 ◽  
Vol 33 (29_suppl) ◽  
pp. 175-175 ◽  
Author(s):  
Jennifer S. Temel ◽  
David Christopher Currow ◽  
Kenneth Fearon ◽  
Ying Yan ◽  
John Friend ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Body Weight ◽  
Small Cell Lung Cancer ◽  
Body Mass ◽  
Fat Mass ◽  
Small Cell ◽  
Small Cell Lung ◽  
Phase 3 ◽  
Total Body Mass ◽  
Total Body

175 Background: Cancer anorexia-cachexia syndrome is common in patients with non-small cell lung cancer (NSCLC). It is characterized by loss of lean body mass (LBM) and negatively impacts quality of life. Anamorelin HCl (ANAM) is a novel investigational ghrelin receptor agonist with anabolic and appetite-enhancing activity. Methods: Two randomized, double-blind, Phase 3 ROMANA 1 (N = 484; NCT01387269) and ROMANA2, (N = 495; NCT01387282) trials assessed ANAM (100 mg) efficacy/safety versus placebo in patients with unresectable stage III/IV NSCLC and cachexia ( ≥ 5% weight loss within prior 6 months or BMI < 20 kg/m2) over 12 weeks. Co-primary endpoints were change from baseline over 12 weeks in LBM and hand grip strength (HGS). Secondary endpoints included changes in body weight and in the anorexia-cachexia subdomain of the Functional Assessment of Anorexia/Cachexia Therapy questionnaire, and pooled survival from ROMANA 1 and 2. Exploratory post-hoc analyses determined change in total body and fat mass from baseline to 12 weeks. Results: Over 12 weeks ANAM significantly increased LBM vs placebo in ROMANA 1 (1.10 vs -0.44 kg, p < 0.001) and ROMANA 2 (0.75 vs -0.96 kg, p < 0.001); HGS was similar in the two arms. In both studies ANAM vs placebo increased body weight (2.20 vs 0.14 kg, p < 0.001; and 0.95 vs -0.57 kg, p < 0.001) and improved anorexia/cachexia symptoms (4.12 vs 1.92, p < 0.001; and 3.48 vs 1.34, p = 0.002). Increases in total body mass (2.87 vs 0.07 kg, p < 0.001; and 2.04 vs -0.59 kg, p < 0.001) and in fat mass (1.21 vs -0.13 kg, p < 0.001; and 0.77 vs 0.09 kg, p = 0.012) were observed for ANAM vs placebo. ANAM was well tolerated; the most frequent drug-related adverse event in ROMANA 1 and 2 was hyperglycemia (5.3% and 4.2%). There was no difference between study arms in median 1-year survival. Conclusions: In two global, Phase 3 studies, ANAM treatment for 12 weeks was well tolerated, and increased LBM, body weight, total body mass and fat mass indicating anabolic activity and suggesting restoration of energy balance in advanced NSCLC patients with cachexia. ANAM also improved anorexia-cachexia symptoms/concerns. Similar pooled survival was observed between the study arms. Clinical trial information: NCT01387269, NCT01387282.

scholarly journals Inflammation status of healthy young men: initial and specific responses to resistance training

2018 ◽  
Vol 43 (3) ◽  
pp. 252-258 ◽  
Author(s):  
Johanna K. Ihalainen ◽  
Heikki Peltonen ◽  
Göran Paulsen ◽  
Juha P. Ahtiainen ◽  
Ritva S. Taipale ◽  
...  
Keyword(s):  
Resistance Training ◽  
Fat Mass ◽  
Lean Mass ◽  
Interleukin 1 ◽  
High Sensitivity ◽  
Abdominal Fat ◽  
Muscle Adaptation ◽  
Monocyte Chemoattractant Protein 1 ◽  
Total Fat ◽  
Total Body

Our primary aim was to study the effects of a 4-week preparatory resistance-training (RT) period followed by 12 weeks of 2 specific RT protocols (either hypertrophic-strength (HS) or strength-hypertrophy-power training) on inflammation markers and the possible relationship of the changes in abdominal fat and lean mass to the changes in inflammation status. A total of 82 healthy men were included in the study. Maximal concentric leg press strength (1-repetition maximum), total body lean mass, total body and abdominal fat mass, circulating high-sensitivity C-reactive protein, interleukin-6, interleukin-1 receptor antagonist (IL-1ra), monocyte chemoattractant protein 1 (MCP-1), and selected adipocytokines (resistin, adiponectin, and leptin) concentrations were measured before and after 4 (wk4) and 16 weeks (wk16) of RT. After the initial phase of RT, on wk4, abdominal and total fat mass as well as plasma leptin concentrations were significantly reduced (p < 0.05), whereas muscle mass, IL-1ra, resistin, and MCP-1 concentrations were significantly increased (p < 0.05). During specialized training phase, at wk16, only HS led to further reduction in abdominal and total fat mass, resistin, and leptin (p < 0.05), whereas both training modes led to lower MCP-1 concentrations (p < 0.05). Abdominal fat mass and circulating leptin were reduced already after 4 weeks of RT. Simultaneously, circulating MCP-1 and resistin concentrations increased, possibly as markers of muscle adaptation and regeneration. The present findings also suggest that RT with hypertrophic focus is beneficial for further reductions in abdominal fat mass and to decrease circulating inflammatory markers.

Growth and Adult Height in Girls With Turner Syndrome Following IGF-1 Titrated Growth Hormone Treatment

2020 ◽  
Vol 105 (8) ◽  
pp. 2566-2574
Author(s):  
Amanda Cleemann Wang ◽  
Casper P Hagen ◽  
Leila Nedaeifard ◽  
Anders Juul ◽  
Rikke Beck Jensen
Keyword(s):  
Growth Hormone ◽  
Turner Syndrome ◽  
Real World ◽  
Adult Height ◽  
Standard Deviation Score ◽  
Fixed Dose ◽  
Dose Titration ◽  
Gh Treatment ◽  
Real World Evidence ◽  
Tertiary Center

Abstract Context Girls with Turner syndrome (TS) suffer linear growth failure, and TS is a registered indication for growth hormone (GH) treatment. GH is classically dosed according to body weight, and serum insulin-like growth factor-1 (IGF-1) concentrations are recommended to be kept within references according to international guidelines. Objective To assess the effect of long-term GH treatment in girls with TS following GH dosing by IGF-1 titration. Design and setting A retrospective, real-world evidence, observational study consisting of data collected in a single tertiary center from 1991 to 2018. Patients A cohort of 63 girls with TS treated with GH by IGF-1 titration with a median duration of 6.7 years (interquartile range [IQR]: 3.4-9.7 years). Main outcome measures Longitudinal measurements of height, IGF-1, and adult height (AH) following GH treatment were evaluated and compared between the different karyotypes (45,X, 45,X/46,XX, or miscellaneous). Results Using GH dose titration according to IGF-1, only 6% of girls with TS had supranormal IGF-1 levels. Median dose was 33 µg/kg/day (IQR: 28-39 µg/kg/day) with no difference between the karyotype groups. AH was reached for 73% who attained a median AH of 1.25 standard deviation score (SDS) for age specific TS references (IQR: 0.64-1.50 SDS), and a median gain in height (ΔHSDS: AH SDS minus baseline height SDS of TS references) of 0.50 SDS, equal to 3.2 cm (SD 7.68) for all karyotypes. Conclusion Our real-world evidence study suggested that titration of GH dose to keep IGF-1 levels within the normal range resulted in a lower AH gain than in studies where a fixed dose was used.

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