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

Phase 4

Completed

• Conditions: Idiopathic Growth Hormone Deficiency; Turner Syndrome
• Interventions: Other: Blood sampling

• Registration Number: NCT01419249
• Lead Sponsor: Merck KGaA, Darmstadt, Germany

Brief 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).

Detailed 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.

Study Timeline

• Study First Submitted: 2011-08-16
• Study First Submitted QC: 2011-08-17
• Study First Posted: 2011-08-18
• Study Start: 2011-09
• Primary Completion: 2012-10
• Study Completion: 2012-10
• Status Verified: 2013-11
• Results First Submitted: 2013-11-26
• Results First Submitted QC: 2013-11-26
• Last Update Submitted: 2013-11-26
• Results First Posted: 2014-01-16
• Last Update Posted: 2014-01-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 458

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

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Retrospective cohort	Blood sampling	-

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Height at Year 1	Baseline and 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.
Height Velocity Standard Deviation Score (SDS) at Year 1	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.
Change From Baseline in Height Standard Deviation Score (SDS) at Year 1	Baseline and 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.

Secondary Outcome Measures

Name	Time	Method
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	Year 1	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.
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	Year 1	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.

Trial Locations

Locations (31)

University Hospital Praha Motol; 🇨🇿 Praha, Czech Republic

University of Calgary - Alberta Children's Hospital; 🇨🇦 Calgary, Canada

Hospital de Niños Ricardo Gutiérrez; 🇦🇷 Buenos Aires, Argentina

Hospital de Pediatria Garrahan; 🇦🇷 Buenos Aires, Argentina

CHU Bordeaux - Hopital pédiatrique Pellegrin; 🇫🇷 Bordeaux, France

Ospedale Microcitemico di Cagliari; 🇮🇹 Cagliari, Italy

Centre d'Endocrinologie Pédiatrique; 🇫🇷 Bordeaux, France

Hôpital Femme-Mère-Enfant; 🇫🇷 Bron, France

University Hospital Hradec Kralove; 🇨🇿 Hradec Kralove, Czech Republic

University of Bari Aldo Moro; 🇮🇹 Bari, Italy

British Columbia Children's Hospital; 🇨🇦 Vancouver, Canada

Centre Hospitalier Universitaire de Sherbrooke - Fleurimont; 🇨🇦 Sherbrooke, Canada

Royal Manchester Children's Hospital; 🇬🇧 Manchester, United Kingdom

Hospital de Niños de la Santisima Trinidad; 🇦🇷 Cordoba, Argentina

CHU Sainte Justine Montréal; 🇨🇦 Montréal, Canada

Fakultní nemocnice Brno; 🇨🇿 Brno, Czech Republic

Faculty Hospital; 🇨🇿 Olomouc, Czech Republic

University of Cologne Children's Hospital; 🇩🇪 Cologne, Germany

University Children's Hospital; 🇩🇪 München, Germany

Centro di Endocrinologia e Diabetologia Pediatrica; 🇮🇹 Catania, Italy

Istituto Giannina Gaslini - Clinica Pediatrica; 🇮🇹 Genova, Italy

Hospital Infantil Universitario Niño Jesús; 🇪🇸 Madrid, Spain

Hospital 12 de Octubre; 🇪🇸 Madrid, Spain

Hospital Universitario Gregorio Maran; 🇪🇸 Madrid, Spain

Hospital Clínico Universitario de Santiago de Compostela; 🇪🇸 Santiago de Compostela, Spain

Hospital Miguel Servet; 🇪🇸 Zaragoza, Spain

Queen Silvia Children's Hospital; 🇸🇪 Göteborg, Sweden

Faculty of Health Sciences, Linkping University; 🇸🇪 Linköping, Sweden

Karolinska University Hospital Campus Solna; 🇸🇪 Stockholm, Sweden

Birmingham Children's Hospital; 🇬🇧 Birmingham, United Kingdom

Sheffield Children's Hospital; 🇬🇧 Sheffield, United Kingdom