Observational Study of Somatropin Treatment in Children

Study Overview
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Brief Summary
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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

Official Title
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The Genetics and Neuroendocrinology of Short Stature International Study (GeNeSIS)

Conditions
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Growth Hormone (GH) Deficiency, Short Stature Homeobox Containing Gene (SHOX) Deficiency, SHOX Deficiency-related Disorder, Non-GH-deficient Growth Disorders

Intervention / Treatment
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* Drug: Somatropin (recombinant deoxyribonucleic acid [rDNA] origin)


Participation Criteria
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Eligibility Criteria
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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. 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.

Ages Eligible for Study
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Minimum Age: 1 Day

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Treated<br>Participants treated with somatropin for improvement of growth | Drug: Somatropin (recombinant deoxyribonucleic acid [rDNA] origin)<br>* Dose, frequency and duration at discretion of attending physician.<br>* Other names: LY137998;|
| Untreated<br>Untreated participants with presence or history of neoplastic disease evaluated for endocrine or growth disorder or with any SHOX deficiency related disorder | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Type 2 Diabetes Mellitus in GH-treated Participants |  | Year 15 | 
| Primary Malignancies in Participant Without Previous Cancer History | Due to the small number of participants involved, untreated and unknown treatment groups, data was not provided and could not be calculated. | Year 15 | 
| Final Height (FH) Gain by Diagnostic Group | 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. | Baseline through Year 15 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Defects in Genes Associated With Pituitary Development | 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). | Baseline through Year 15 | 
| Predicted First Year Height Gain Versus Actual First Year Height Gain | 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 | Baseline through Year 15 | 
| Change From Baseline to Final Height in Anthropometric Measures for Participants With SHOX Deficiency |  | Baseline, Year 15 | 
| Percentage of Participants With Recurrent Neoplasms and Second Neoplasms in Childhood Cancer Survivors | Percentage of participants with recurrence/progression of primary neoplastic disease and/or development of secondary neoplasms in childhood cancer survivors. | Baseline through Year 15 | 
| Percentage of Participants With De Novo Neoplasms | Percentage of participants with the development of de novo neoplastic disease with no history of prior neoplasia. | Baseline through Year 15 | 
| Diabetes Mellitus (DM) in Somatropin-Treated Children With Different Short Stature Diagnoses |  | Baseline through Year 15 |