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

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).

Study Overview

• Status: Completed
• Conditions: Turner Syndrome; Idiopathic Growth Hormone Deficiency
• Intervention / Treatment: Other: Blood sampling

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 Type: Interventional
• Enrollment (Actual): 458
• Phase: Phase 4

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Retrospective cohort	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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

Collaborators and Investigators

• Sponsor: Merck KGaA, Darmstadt, Germany
• Collaborators: Merck Serono S.A., Geneva
• Investigators: Study Director: Gilles Della Corte, Merck Serono S.A. , Geneva, Switzerland

Study record dates

Study Major Dates

• Study Start: September 1, 2011
• Primary Completion (Actual): October 1, 2012
• Study Completion (Actual): October 1, 2012

Study Registration Dates

• First Submitted: August 16, 2011
• First Submitted That Met QC Criteria: August 17, 2011
• First Posted (Estimate): August 18, 2011

Study Record Updates

• Last Update Posted (Estimate): January 16, 2014
• Last Update Submitted That Met QC Criteria: November 26, 2013
• Last Verified: November 1, 2013

More Information

Terms related to this study

• Keywords: Growth Hormone Deficiency; Pharmacogenetics; Turner syndrome; Recombinant Human Growth Hormone therapy
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Endocrine System Diseases; Disease; Gonadal Disorders; Disorders of Sex Development; Urogenital Abnormalities; Congenital Abnormalities; Genetic Diseases, Inborn; Heart Defects, Congenital; Cardiovascular Abnormalities; Chromosome Disorders; Sex Chromosome Disorders; Sex Chromosome Disorders of Sex Development; Syndrome; Turner Syndrome; Gonadal Dysgenesis
• Other Study ID Numbers: EMR 200104_010