hrp0086fc8.1 | Growth: Clinical | ESPE2016

Transcriptomics and Machine Learning Methods Accurately Predict Diagnosis and Severity of Childhood Growth Hormone Deficiency

Murray Philip , Stevens Adam , Koledova Ekaterina , Chatelain Pierre , Clayton Peter

Background: The diagnosis of Growth Hormone Deficiency (GHD) involves the use of GH stimulation tests that require day case admission, multiple blood sampling and are associated with significant adverse effects.Aim: To assess the utility of gene expression (GE) profiling and candidate SNP analysis for the diagnosis of and classification of GHD.Method: Pre-pubertal treatment-naïve children with GHD (n=98) were enrolled from the...

hrp0086rfc8.6 | Growth: Clinical | ESPE2016

A Six-Month Safety and Efficacy Study of TransCon hGH Compared to Daily hGH in Pre-Pubertal Children with Growth Hormone Deficiency (GHD)

Chatelain Pierre , Malievsky Oleg , Radziuk Klaudziya , Senatorova Ganna , Beckert Michael

Background: TransCon hGH is a long-acting prodrug of recombinant human growth hormone (hGH) that releases fully active unmodified hGH into the blood compartment. This presentation will detail the final safety and efficacy results of TransCon hGH in a Phase 2 study in children with GHD over a treatment period of six months.Objective and hypotheses: The objective of this Phase 2 study in GHD was to investigate 1) safety and tolerability, 2) pharmacokinetic...

hrp0086rfc14.5 | Growth : Mechanisms | ESPE2016

Gene Expression Profiling of Children with GH Deficiency (GHD) Prior to Treatment with Recombinant Human Growth Hormone (r-hGH) is Associated with Growth Response Over Five Years of Therapy

Stevens Adam , Murray Philip , Koledova Ekaterina , Chatelain Pierre , Clayton Peter

Background: The relationship of pre-treatment gene expression (GE) to long-term growth response in GHD is unknown. Prediction of long-term response to r-hGH therapy would allow better decision making about start and maintenance doses and hence cost:benefit.Objective and hypotheses: To assess the relationship of baseline GE to response to r-hGH over 5 years of therapy in GHD children.Method: Pre-pubertal children with GHD (n</em...

hrp0086p1-p603 | Growth P1 | ESPE2016

Pediatric Phase 2 Data Demonstrate that TransCon hGH Has an Anti-hGH Immunogenic Profile that is Comparable to Daily hGH

Gilfoyle David , Pihl Susanne , Chatelain Pierre , Beckert Michael

Background: TransCon hGH, is a once-weekly prodrug releasing unmodified hGH, for the treatment of Growth Hormone Deficiency (GHD) in children and adults. To date, TransCon hGH has demonstrated comparable efficacy, safety and anti-hGH immunogenic profile to daily hGH, with no occurrence of neutralizing antibodies.Objective and hypotheses: Protein-based therapies may be associated with generation of drug-specific antibodies, which may impact efficacy, part...

hrp0082fc7.3 | Growth promoting therapies | ESPE2014

Gene Expression Networks Associated with Changes in Serum Markers of Metabolism and Growth in GH-Treated Children with GH Deficiency

Stevens Adam , De Leonibus Chiara , Chatelain Pierre , Clayton Peter

Introduction: Growth promoting effects of GH occur in parallel with its impact on insulin sensitivity and lipid metabolism; underlying biological networks that link these actions are not defined. Our objective was to identify gene expression (GE) networks linking growth with metabolic responses in GH-treated children with GHD.Methods/design: Pre-pubertal children with GH Deficiency GHD (n=125) were enrolled from the PREDICT short-term (NCT002561...

hrp0084p2-407 | GH &amp; IGF | ESPE2015

A Phase 2, 6-Month, Randomised, Active-Controlled, Safety and Efficacy Study of TransCon hGH Compared to Daily Human GH in Children with GH Deficiency

Chatelain Pierre , Malievsky Oleg , Radziuk Klaudziya , Senatorova Ganna , Beckert Michael

Background: TransCon human GH (hGH) is a long-acting prodrug of recombinant hGH that releases fully active unmodified hGH. TransCon hGH was shown in phase 1 studies in healthy volunteers and a phase 2 study in adults with hGH deficiency to: i) be safe and well tolerated, ii) provide dose-dependent hGH levels, with same peak level and exposure compared to daily GH, iii) be suitable for a once-weekly dosing regimen, and iv) induce an IGF1 response within the normal range. This o...

hrp0084p1-83 | Growth Hormone | ESPE2015

Genetic Markers Contribute to the PREDICTION of Response to GH in Severe but not Mild GH Deficiency

Stevens Adam , Murray Philip , Wojcik Jerome , Raelson John , Koledova Ekaterina , Chatelain Pierre , Clayton Peter

Background: Single nucleotide polymorphisms (SNPs) associated with the response to GH therapy have previously been identified in growth hormone deficient (GHD) children in the PREDICT long-term follow-up (LTFU) study (NCT00699855).Objective and hypotheses: To assess the effect of GHD severity on the predictive value of genetic markers of growth response.Method: We used pre-pubertal GHD children (peak GH <10 μg/l) from the ...

hrp0082p1-d3-165 | Growth (2) | ESPE2014

Validating Genetic Markers of Response to Recombinant Human GH in Children with GH Deficiency or Turner Syndrome: Results From the PREDICT Validation Study

Chatelain Pierre , Stevens Adam , De Leonibus Chiara , Clayton Peter , Wojcik Jerome

Introduction: Genetic markers associated with the response to recombinant human GH (r-hGH) have been identified in Growth Hormone Deficiency (GHD) and Turner Syndrome (TS) children in the PREDICT long-term follow-up (LTFU) prospective study (NCT00699855).1 A validation (VAL) study (NCT01419249) was conducted to confirm association.Methods/design: Inclusion criteria for GHD and TS children were identical in the LTFU and VAL studies (GHD defined...

hrp0084p2-394 | GH &amp; IGF | ESPE2015

Gene Expression Profiles in GH Deficient Children Relate Peak GH Levels to Circadian Clock, Chromatin Remodelling, and WNT Signalling Pathways

Murray Philip , Stevens Adam , DeLeonibus Chiara , Koledova Ekaterina , Chatelain Pierre , Clayton Peter

Background: GH deficiency (GHD) is classically defined on the basis of a cut-off applied to the peak GH level during stimulation tests; a process with recognised limitations. Identifying the functional role of genes whose expression is associated with pGH may help with our understanding and classification of GHD.Objective and hypotheses: Identify patterns of gene expression (GE) related to pGH and to describe the function, and regulation of these genes.<...

hrp0084p2-418 | GH &amp; IGF | ESPE2015

Random Forest Classification Predicts Response to Recombinant GH in GH Deficient Children Using Baseline Clinical Parameters and Genetic Markers

Stevens Adam , Murray Philip , Wojcik Jerome , Raelson John , Koledova Ekaterina , Chatelain Pierre , Clayton Peter

Background: Prediction of response to recombinant GH (r-GH) is currently based on regression modelling. This approach generates a prediction equation which can be applied to data from an individual child. However this method can underestimate the effect of inter-dependent variables. Random forest classification (RFC) is an alternative prediction method based on decision trees that is not sensitive to the relationships between variables.Objective and hypo...