First Year Growth Response Associated Genetic Markers Validation Phase IV Open-label Study in Growth Hormone Deficient and Turner Syndrome Pre-pubertal Children: the PREDICT Pharmacogenetics Validation Study

Turner Syndrome Clinical Trial

Official title:

First Year Growth Response Associated Genetic Markers Validation Phase IV Open-label Study in Growth Hormone Deficient and Turner Syndrome Pre-pubertal Children: the PREDICT Pharmacogenetics Validation Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01419249
• Other study ID #: EMR 200104_010
• Status: Completed
• Phase: Phase 4
• First received: August 16, 2011
• Last updated: November 26, 2013
• Start date: September 2011
• Est. completion date: October 2012

Study information

• Verified date: November 2013
• Source: Merck KGaA
• Contact: n/a
• Is FDA regulated: No
• Health authority: Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia MedicaCanada: Ethics Review CommitteeCzech Republic: State Institute for Drug ControlFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)France: Institutional Ethical CommitteeGermany: Ethics CommissionItaly: Ethics CommitteeSpain: Comité Ético de Investigación ClínicaSpain: Ministry of HealthSweden: Regional Ethical Review BoardSweden: Data Inspection AgencySweden: Biobank Center of Västra Götaland and Sydöstra sjukvardsregionenUnited Kingdom: Medicines and Healthcare Products Regulatory AgencyUnited Kingdom: National Health ServiceUnited Kingdom: Research Ethics Committee
• Study type: Interventional

Clinical Trial Summary

PREDICT Validation is a validation pharmacogenetic trial. The purpose of this study is to confirm that some genes can be used to predict how well a subject diagnosed with idiopathic growth hormone deficiency (IGHD) or turner syndrome (TS) will respond to a treatment with recombinant human growth hormone (r-hGH).

Description:

This study is an open-label, interventional, retrospective, multicenter, international study, single-arm, non-randomized, and non-controlled study. The subject's trial participation includes a single visit. During the visit, subjects who give consent to participate in the trial will undergo blood sampling for genetic markers testing and retrospective data will be collected relative to the first year of the subject's r-hGH treatment.

The r-hGH treatment followed by the subject is indicated the pediatric population, therefore most of the subjects included into the trial will be below 18 years old.

This study is a non-investigational medicinal product (IMP) trial therefore no drug product data is provided.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 458
• Est. completion date: October 2012
• Est. primary completion date: October 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 18 Years

Eligibility

Inclusion Criteria:

• Pre-established diagnosis of IGHD or TS based on classical criteria with at least 1 year of r-hGH therapy and with Tanner stage 1 at treatment start

• Retrospective availability of a complete set of clinical, auxological and biological parameters necessary for building the predictive model

• Other protocol defined inclusion criteria could apply

Exclusion Criteria:

• Acquired growth hormone deficiency (GHD)

• Any drug or disease that could affect growth during the first year of r-hGH treatment

• Other protocol defined exclusion criteria could apply

Study Design

Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Dwarfism, Pituitary
• Endocrine System Diseases
• Gonadal Dysgenesis
• Idiopathic Growth Hormone Deficiency
• Primary Ovarian Insufficiency
• Syndrome
• Turner Syndrome

Intervention

Other:
• Blood sampling
Subjects with pre-established diagnosis of IGHD and TS and were treated with r-hGH therapy for 1 year, will be observed in this retrospective cohort study wherein blood sampling will performed for genotyping of the various genetic markers along with collection of retrospective data relative to the r-hGH treatment.

Locations

Country	Name	City	State
Argentina	Hospital de Niños Ricardo Gutiérrez	Buenos Aires
Argentina	Hospital de Pediatria Garrahan	Buenos Aires
Argentina	Hospital de Niños de la Santisima Trinidad	Cordoba
Canada	University of Calgary - Alberta Children's Hospital	Calgary
Canada	CHU Sainte Justine Montréal	Montréal
Canada	Centre Hospitalier Universitaire de Sherbrooke - Fleurimont	Sherbrooke
Canada	British Columbia Children's Hospital	Vancouver
Czech Republic	Fakultní nemocnice Brno	Brno
Czech Republic	University Hospital Hradec Kralove	Hradec Kralove
Czech Republic	Faculty Hospital	Olomouc
Czech Republic	University Hospital Praha Motol	Praha
France	Centre d'Endocrinologie Pédiatrique	Bordeaux
France	CHU Bordeaux - Hopital pédiatrique Pellegrin	Bordeaux
France	Hôpital Femme-Mère-Enfant	Bron
Germany	University of Cologne Children's Hospital	Cologne
Germany	University Children's Hospital	München
Italy	University of Bari Aldo Moro	Bari
Italy	Ospedale Microcitemico di Cagliari	Cagliari
Italy	Centro di Endocrinologia e Diabetologia Pediatrica	Catania
Italy	Istituto Giannina Gaslini - Clinica Pediatrica	Genova
Spain	Hospital 12 de Octubre	Madrid
Spain	Hospital Infantil Universitario Niño Jesús	Madrid
Spain	Hospital Universitario Gregorio Maran	Madrid
Spain	Hospital Clínico Universitario de Santiago de Compostela	Santiago de Compostela
Spain	Hospital Miguel Servet	Zaragoza
Sweden	Queen Silvia Children's Hospital	Göteborg
Sweden	Faculty of Health Sciences, Linkping University	Linköping
Sweden	Karolinska University Hospital Campus Solna	Stockholm
United Kingdom	Birmingham Children's Hospital	Birmingham
United Kingdom	Royal Manchester Children's Hospital	Manchester
United Kingdom	Sheffield Children's Hospital	Sheffield

Sponsors (2)

Lead Sponsor	Collaborator
Merck KGaA	Merck Serono S.A., Geneva

Countries where clinical trial is conducted

Argentina,  Canada,  Czech Republic,  France,  Germany,  Italy,  Spain,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Height at Year 1	Change from baseline in height at year 1 was one of the growth parameter to assess the first year growth response to r-hGH treatment.	Baseline and Year 1	No
Primary	Change From Baseline in Height Standard Deviation Score (SDS) at Year 1	Height SDS was calculated as height minus reference mean height divided by standard deviation of the reference population. Height SDS reflects the height relative to a reference population of the same age and gender. Change from baseline in height SDS at Year 1 was one of the growth parameter to assess the first year growth response to r-hGH treatment.	Baseline and Year 1	No
Primary	Height Velocity Standard Deviation Score (SDS) at Year 1	Height velocity SDS was calculated as height velocity minus reference mean height velocity divided by standard deviation of the reference population. Height velocity SDS reflects the height velocity relative to a reference population of the same age and gender. Height velocity SDS at Year 1 was one of the growth parameter to assess the first year growth response to r-hGH treatment.	Year 1	No
Secondary	Evaluation of the Contribution of Validated Genetic Markers to the Amplitude of First Year Growth Response to r-hGH Therapy in IGHD Children Using Growth Hormone Deficiency Kabi-Pharmacia International Growth Study (GHD KIGS) Predictive Model	GHD KIGS predictive model includes various clinical, auxological and biological markers which are as follows: maximum growth hormone (GH) response to provocation test; age at onset of therapy; birth weight SDS; average GH dose received during the first year of r-hGH therapy; height SDS at start of therapy; the difference between the pre-treatment height SDS of the subject and the mid parental height SDS; and weight SDS at start of therapy.	Year 1	No
Secondary	Evaluation of the Contribution of Validated Genetic Markers to the Amplitude of First Year Growth Response to r-hGH Therapy in TS Girls Using Turner Syndrome Kabi-Pharmacia International Growth Study (TS KIGS) Predictive Model	TS KIGS predictive model includes various clinical, auxological and biological markers which are as follows: maximum GH response to provocation test; age at onset of therapy; birth weight SDS; average GH dose received during the first year of r-hGH therapy; height SDS at start of therapy; the difference between the pre-treatment height SDS of the subject and the mid parental height SDS; and weight SDS at start of therapy.	Year 1	No