Long-term Safety Follow-up After Growth Hormone Treatment of Short Children Born Small for Gestational Age

Study Overview
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Brief Summary
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This study is performed as part of the Marketing Authorisation Holder's post-marketing pharmacovigilance plan to investigate the long-term safety, in particular the diabetogenic potential and immunogenicity of rhGH therapy in short children born small for gestational age (SGA).

Detailed Description
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The purpose of this study is to monitor short children born SGA who were treated with growth hormone in study EP00-401 for the development of diabetes for a further 10 years after termination of growth hormone treatment and to report the incidence of anti-rhGH antibodies and of E. coli host cell peptide (HCP) antibodies (ABs) for 6 months after termination of GH treatment.

Official Title
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Long-term Safety Follow-up After Growth Hormone Treatment (rhGH) of Short Children Born Small for Gestational Age (SGA)

Conditions
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Short Children Born Small for Gestational Age (SGA)

Intervention / Treatment
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* Other: Bloodsampling


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All patients who fulfilled the diagnosis SGA, participated in study EP00-401, and received at least one dose of study medication Written informed consent of patient (for children who can read and/ or understand) and/or parent or legal guardian Exclusion Criteria: Patients unwilling and/or parents/guardians who are not capable of ensuring compliance with the provisions of the study protocol

Ages Eligible for Study
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Minimum Age: 4 Years

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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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Monitoring of long-term safety<br>Long-term safety follow-up after the end of treatment with Omnitrope (single arm) | Other: Bloodsampling<br>* Bloodsampling<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate the Long-term Effect of Growth Hormone Treatment on the Development of Diabetes After End of Therapy. | Number of participants diagnosed with Diabetes mellitus type 2 during the study, defined as fullfilment of these 3 criteria: FPG ≥ 126 mg/dl (7.0 mmol/L) during blood sampling and/or during Oral Glucose Tolerance Test (OGTT) 2-h plasma glucose ≥ 200 mg/dl (11.1 mmol/L) during an OGTT Investigator documenting diagnosis of diabetes mellitus type 2 during OGTT | 5 years | 
| To Evaluate the Long Term Effects of rhGH on Carbohydrate Metabolism Through Fasting Plasma Glucose (FPG) Levels | Supportive to Primary Endpoint | baseline, 6 months, 1 year, 5 years | 
| To Evaluate the Long Term Effects of rhGH on Carbohydrate Metabolism Through Fasting Insulin Levels | Supportive to Primary Endpoint | baseline, 6 months, 1 year, 5 years | 
| To Evaluate the Long Term Effects of rhGH on Carbohydrate Metabolism Through Glucose Glycolsylated Hemoglobin (HbA1c) | Supportive to Primary Endpoint | baseline, 6 months, 1 year, 5 years | 
| To Evaluate the Long Term Effects of rhGH on Carbohydrate Metabolism Through HOMA and QUICKI Scores | Supportive to Primary Endpoint. HOMA = homeostasis model assessment for Insulin resistance: Healthy Range: 1.0 (0.5-1.4). < 1.0 means you are insulin-sensitive which is optimal. >1.9 indicates early insulin resistance. > 2.9 indicates significant insulin resistance. The quantitative insulin sensitivity check index (QUICKI) measures insulin sensitivity, which is the inverse of insulin resistance. The QUICKI calculation for insulin resistance in humans fall broadly within a range between 0.45 for unusually healthy individuals and 0.30 in diabetics. Lower numbers reflect greater insulin resistance. | baseline, 6 months, 1 year, 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| to Evaluate IGF-I and IGFBP-3 Levels After End of Growth Hormone Treatment |  | baseline, 6 months, 1 year , 5 years | 
| To Evaluate the Incidence of Anti-rhGH Antibodies After Termination of Growth Hormone Treatment. | number of participants with positive results for anti-drug antibody (ADA). Percentages indicated are calculated based on the total number of patients (118 participants). | baseline, 6 months, 1 year, 5 years | 
| to Evaluate Final Height |  | baseline, 6 months, 1 year, 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Long-term, safety, follow-up, growth hormone treatment, short children, Small for Gestational Age, Somatropin