hrp0089p2-p218 | GH & IGFs P2 | ESPE2018

The Rationale and Design of TransCon GH

Sprogoe Kennett , Beckert Michael , Mortensen Eva , Karpf David B , Leff Jonathan A

Background: The fundamental challenge of developing a long-acting growth hormone (LAGH) is to create a more convenient growth hormone (GH) dosing profile while retaining the excellent safety, efficacy, and tolerability of daily GH. With GH receptors on virtually all cells, replacement therapy should achieve the same tissue distribution and effects of daily (and endogenous) GH while maintaining levels of GH and resulting IGF1 within the physiologic range....

hrp0089p2-p219 | GH & IGFs P2 | ESPE2018

Baseline Demographics of the TransCon GH Phase 3 heiGHt Trial

Beckert Michael , Karpf David B , Shu Aimee , Lin Zhengning , Leff Jonathan A

Background: TransCon GH is a novel sustained-release recombinant human GH (somatropin) prodrug in development for children with GH deficiency (GHD). It is designed to release unmodified GH and intended to provide comparable efficacy, safety, tolerability, and immunogenicity to daily GH with once-weekly dosing. Based on results from a phase 2 trial, which demonstrated comparable efficacy (annualized height velocity for TransCon 0.21 mg GH/kg per week of 12.9 cm/year vs 11.6 cm/...

hrp0086rfc4.5 | Pathophysiology of Obesity | ESPE2016

Steroid Metabolomic Signature of Liver Disease in Childhood Obesity

Gawlik Aneta , Shmoish Michael , Hartmann Michaela F. , Malecka-Tendera Ewa , Wudy Stefan A. , Hochberg Ze'ev

Background: Analysis of steroids by gas chromatography-mass spectrometry (GC-MS) defines a subject’s steroidal fingerprint. Here, we compare the steroidal fingerprints of obese children with or without liver disease to identify the ‘steroid metabolomic signature’ of childhood non-alcoholic fatty liver disease.Methods: Urinary samples of 85 children (43 girls) age 8.5–18.0 with obesity (BMI >97%) were quantified for 31 steroid meta...

hrp0086rfc8.2 | Growth: Clinical | ESPE2016

Pharmacokinetic Modelling Predicts Native hGH Levels Following Administration of a Sustained-Release Prodrug, TransCon hGH, to Children with GHD

Sprogoe Kennett , Beckert Michael , Christoffersen Eva Dam , Gilfoyle David , Wegge Thomas

Background: TransCon Growth Hormone is a once-weekly sustained-release prodrug of recombinant human growth hormone (hGH, somatropin). Based on the inert TransCon prodrug technology unmodified hGH is released with a Cmax and AUC comparable to daily therapy. TransCon hGH leverages the known pharmacology of daily hGH and is being developed for the treatment of growth hormone deficiency (GHD).Objective and hypotheses: Both hGH levels and resulting IGF-I leve...

hrp0086p1-p203 | Diabetes P1 | ESPE2016

Diabetes Mellitus Caused by Bone Marrow Transplantation and Total Body Irradiation – Experience from a Regional Single Centre

Candler Toby , Wei Christina , Bradley Karin , Cox Rachel , Elson Ruth , Stevens Michael , Crowne Elizabeth

Background: Diabetes is a recognised long term sequelae in childhood cancer survivors following bone marrow transplantation and total body irradiation (BMT/TBI), due to a combination of insulin deficiency and resistance.Aim: To characterise presentation, treatment and clinical course of diabetes in childhood leukaemia survivors post BMT/TBI.Method: A single centre retrospective case note review of diabetes post BMT/TBI identified f...

hrp0086p1-p210 | Diabetes P1 | ESPE2016

Screening for Liver Disease in Children and Adolescents with Type 1 Diabetes Mellitus: A Cross-sectional Analysis

Kummer Sebastian , Klee Dirk , Kircheis Gerald , Friedt Michael , Schaper Joerg , Haussinger Dieter , Mayatepek Ertan , Meissner Thomas

Background: The liver is one of the most important organs in glucose metabolism and closely related to diabetes pathophysiology. Non-alcoholic fatty liver disease (NAFLD) is well known in type 2 diabetes mellitus (DM), but also adult patients with type 1 DM are at increased risk for NAFLD.Objective and hypotheses: Here, we studied the prevalence of liver disease in a representative number of children and adolescents with type 1 DM in Germany.<p class...

hrp0086p1-p618 | Growth P1 | ESPE2016

Design and Clinical Development of TransCon Growth Hormone for Growth Hormone Deficiency (GHD)

Beckert Michael , Gilfoyle David , Mikkelsen Jan Moller , Rasmussen Grethe , Rau Harald , Sprogoe Kennett

Background: TransCon GH is designed as a once-weekly sustained-release prodrug of recombinant human GH (hGH, somatropin). Based on the inert TransCon prodrug technology unmodified native hGH is released with a Cmax and AUC comparable to daily therapy. TransCon GH leverages the known pharmacology of daily hGH and is being developed for the treatment of GH deficiency (GHD) in children and adults.Objective and hypotheses: Develop a safe and efficacious sust...

hrp0086p2-p671 | Growth P2 | ESPE2016

Assessing Disease and Treatment Burden for Young Children with Growth Hormone Deficiency (GHD)

Brod Meryl , Wilkinson Lars , Alolga Suzanne Lessard , Hojbjerre Lise , Beck Jane , Rasmussen Michael Hojby

Background: Children with GHD, in addition to short stature, may experience physiological symptoms as well as social and emotional problems. Assessing these impacts is critical for understanding the extent of GHD burden and assessing treatment benefit. Since many children initiating treatment are too young to self-report information, we must rely on adult reporters. However, according to FDA guidelines and established measure development principles, adult reporter information ...

hrp0086p1-p751 | Pituitary and Neuroendocrinology P1 | ESPE2016

Transcriptional Basis of Idiopathic Central Hypogonadism in Isolated Congenital Cryptorchidism with Defective Mini-Puberty

Hadziselimovic Faruk , Gegenschatz Katharina , Verkauskas Gilvydas , Demougin Philippe , Stadler Michael , Bilius Vytautas , Malcius Dalius , Dasevicius Darius

Objective and hypotheses: The objective was to use whole-genome RNA profiling of testicular biopsies by DNA strand-specific RNA-sequencing to explore the causative role of isolated congenital cryptorchidism in azoospermia and/or infertility.Method: Fifteen cryptorchid patients, aged 7 months to 5 years, were enrolled in this study and underwent orchidopexy. During surgery, testicular tissue biopsies were collected and split in half for histological exami...

hrp0086p1-p804 | Syndromes: Mechanisms and Management P1 | ESPE2016

Near-Adult Height in a Large Cohort of Patients with Turner Syndrome and Noonan Syndrome Treated with rhGH: Results from Pfizer International Growth Database

Ranke Michael , Lindberg Anders , Camacho-Hubner Cecilia , Reinehr Thomas , Rooman Raoul

Background: Pfizer International Growth Database (KIGS) contains data of Turner syndrome (TS; N=7378) or Noonan syndrome (NS; N=613, female=224; male=389) patients who were treated with rhGH.Objective: To compare the effect of rhGH on near adult height (NAH) in TS and NS patients. We hypothesized a similar outcome in both diagnoses. Determinants of the treatment outcome in NS patients were also assessed.Patients a...