Observational Study of Somatropin Treatment in Children

Completed

• Conditions: Short Stature Homeobox Containing Gene (SHOX) Deficiency; SHOX Deficiency-related Disorder; Non-GH-deficient Growth Disorders; Growth Hormone (GH) Deficiency
• Interventions: Drug: Somatropin (recombinant deoxyribonucleic acid [rDNA] origin)

• Registration Number: NCT01088412
• Lead Sponsor: Eli Lilly and Company

Brief Summary

GeNeSIS is an open-label, multinational, multicenter, observational study to evaluate the safety and effectiveness of Humatrope treatment.

GeNeSIS is a modular program that includes:

* Core study: Evaluating the safety and effectiveness of Humatrope in the observational setting

* Genetic Analysis Sub-study: Investigating the genetic defects underlying growth hormone (GH) deficiency and non-GH-deficient growth disorders

* Growth Prediction Sub-study: Working to validate and refine specific models to accurately predict growth response to GH

* Short Stature Homeobox containing gene (SHOX) Deficiency Sub-study: Elucidating the clinical, endocrine and radiological features of participants with SHOX deficiency due to loss of, or mutation in the SHOX gene (including participants with Turner syndrome)

* Neoplasia Sub-study: To characterize the natural history of neoplastic disease, especially in relation to recurrence/progression of primary neoplasia or development of secondary neoplasia in children with a history of neoplasia

Detailed Description

Not available

Study Timeline

• Study Start: 1999-04
• Study First Submitted: 2010-02-25
• Study First Submitted QC: 2010-03-16
• Study First Posted: 2010-03-17
• Primary Completion: 2015-09
• Study Completion: 2015-09
• Results First Submitted: 2016-09-28
• Status Verified: 2018-07
• Results First Submitted QC: 2019-02-11
• Last Update Submitted: 2019-02-11
• Results First Posted: 2019-05-13
• Last Update Posted: 2019-05-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 22845

Inclusion Criteria

All participants participating in GeNeSIS must be enrolled in the core study. Participants for whom written consent to release information is provided may enter the core study if they meet any of the following inclusion guidelines:

• Treatment with Humatrope for improvement of growth.
• No treatment with somatropin in participants with a history of neoplasia or in those with any SHOX deficiency-related disorder.

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Exclusion Criteria

• Participants with closed epiphyses are not eligible for GeNeSIS entry. However, participants may remain in the study if epiphyseal closure occurs during study participation.

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Treated	Somatropin (recombinant deoxyribonucleic acid [rDNA] origin)	Participants treated with somatropin for improvement of growth

Primary Outcome Measures

Name	Time	Method
Type 2 Diabetes Mellitus in GH-treated Participants	Year 15
Final Height (FH) Gain by Diagnostic Group	Baseline through Year 15	The standard deviation score (SDS) reports the number of standard deviations from the mean for age and sex for an individual measurement (normal range is -2 to +2 SDS). Height SDS is derived by subtracting the population mean from individual's height value and then dividing that difference by the population standard deviation. Greater height SDS values indicate greater height. Due to the small number of participants involved, untreated and unknown treatment groups, data was not provided and could not be calculated.
Primary Malignancies in Participant Without Previous Cancer History	Year 15	Due to the small number of participants involved, untreated and unknown treatment groups, data was not provided and could not be calculated.

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants With Recurrent Neoplasms and Second Neoplasms in Childhood Cancer Survivors	Baseline through Year 15	Percentage of participants with recurrence/progression of primary neoplastic disease and/or development of secondary neoplasms in childhood cancer survivors.
Change From Baseline to Final Height in Anthropometric Measures for Participants With SHOX Deficiency	Baseline, Year 15
Percentage of Participants With Defects in Genes Associated With Pituitary Development	Baseline through Year 15	Percentage of participants with genetic defects associated with pituitary development. Genes included but were not limited to GH1, Growth hormone releasing hormone receptor (GHRHR), Homeobox gene expressed in embryonic stem cells (HESX1), LIM homeobox 3 (LHX3), POU domain, class 1, transcription factor 1 (POU1F1), and Prophet of Pit1 (PROP1).
Predicted First Year Height Gain Versus Actual First Year Height Gain	Baseline through Year 15	The value for predicted and observed is of limited bearing, it is how each participant's predicted versus observed height gain compare and this is best estimated by the R-squared. An estimation parameter would not be a correct format for the R2 data. R2 can take value between 0 and 1 with values closer to 0 representing a poor fit while values closer to 1 representing a perfect fit
Percentage of Participants With De Novo Neoplasms	Baseline through Year 15	Percentage of participants with the development of de novo neoplastic disease with no history of prior neoplasia.
Diabetes Mellitus (DM) in Somatropin-Treated Children With Different Short Stature Diagnoses	Baseline through Year 15