A Post-Marketing Study of the Immunogenicity of Somatropin (Ribosomal Deoxyribo Nucleic Acid [rDNA] Origin) Injection (Nutropin AQ®) in Children With Growth Hormone Deficiency

Study Overview
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Brief Summary
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This is a Phase IV, multicenter, open-label, single-arm study of somatropin (rDNA origin) (Nutropin AQ v1.1) in pre-pubertal children with growth hormone deficiency (GHD) naïve to prior recombinant human growth hormone (rhGH) treatment. The study is designed to characterize the immunogenicity profile of somatropin (rDNA origin) injection when administered daily subcutaneously for 12 months. The clinical impact of immunogenicity will also be assessed.

Official Title
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A Phase IV, Multicenter, Open-Label Study of the Immunogenicity of Nutropin AQ® V1.1 [Somatropin (rDNA Origin) Injection] Administered Daily to Naïve Growth Hormone-Deficient Children (iSTUDY)

Conditions
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Growth Hormone Deficiency

Intervention / Treatment
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* Drug: Somatropin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Bone age less than equal to (</=) 9 years (females) or </= 11 years (males) as determined by X-ray of the left hand and wrist using Greulich and Pyle method and obtained within the 12 months prior to enrollment Prepubertal (Tanner I) males and females by physical examination Diagnosis of GHD (stimulated GH less than [<] 10 nanograms per milliliter [ng/mL]) by two standard pharmacologic tests obtained up to 12 months prior to informed consent/assent Normal thyroid function test within the 12 months prior to informed consent/assent Normal complete blood counts within 12 months prior to informed consent/assent Documentation of prior height and weight measurements, with height standard deviation score (SDS) </= 5th percentile for idiopathic isolated GHD participants Exclusion Criteria: Any previous rhGH treatment Short stature etiologies other than GHD Acute critical illness or uncontrolled chronic illness, which in the opinion of the investigator and medical monitor, would interfere with participation in this study, interpretation of the data, or pose a risk to participant safety Chronic illnesses such as inflammatory bowel disease, celiac disease, heart disease, and diabetes Bone diseases such as achondroplasia or hypochondroplasia, intracranial tumor, irradiation, and traumatic brain injury Participants receiving oral or inhaled chronic corticosteroid therapy (greater than [>] 3 months) for other medical conditions other than central adrenal insufficiency Participants who require higher (2 times or greater than maintenance) doses of corticosteroids for more than 5 days in the 6 months prior to enrollment in the study Participants with active malignancy or any other condition that the investigator believes would pose a significant hazard to the participant if rhGH were initiated Females with Turner syndrome regardless of their GH status Prader-Willi syndrome regardless of GH status Born small for gestational age regardless of GH status Presence of scoliosis requiring monitoring Previous participation in another clinical trial or investigation of GH, treatment for growth failure, or treatment with a biologic agent Participants with closed epiphyses Participants with a known hypersensitivity to somatropin, excipients, or diluent

Ages Eligible for Study
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Minimum Age: 3 Years
Maximum Age: 14 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: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Somatropin<br>Children will receive daily SC injections of somatropin at a dose of up to 0.043 milligrams per kilogram per day (mg/kg/day) for 1 year. | Drug: Somatropin<br>* Somatropin will be administered as SC injections at a dose of up to 0.043 mg/kg/day. The dose may be adjusted for a change in body weight of at least (plus [+]/minus [-]) 2 kilograms (kg) from baseline at the Month 6 study visit or for a change in insulin-growth factor-1 (IGF-1), as per investigator assessment.<br>* Other names: Nutropin AQ v1.1;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Develop Anti-GH Antibodies After Treatment With Nutropin AQ v1.1 | Participants who were tested positive to anti-GH antibody after initiation of study treatment. | Baseline up to 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Exhibit Functional Growth Attenuation | Growth attenuation is defined as initial growth response greater than pretreatment velocity followed by reduction in growth response to below the pretreatment velocity in the subsequent 6- to 12-month treatment period or reaching ≤ 2 cm per year. | Baseline up to 1 year | 
| Percentage of Participants With Neutralizing Antibodies | Among participants who developed positive anti-GH antibody post-baseline, participants who were tested positive to neutralizing anti-GH antibody during study participation. | Baseline up to 1 year | 
| Annualized Growth Velocity at Months 6 and 12 (Change From Baseline) | Annualized growth velocity is defined as (height - baseline height) / (date of height assessment - date of baseline)*365.25. Results are presented according to anti-GH antibody status (positive included all participants that were anti-GH antibody positive at least once post-baseline visit and anti-GH antibody negative population included all participants that were anti-GH antibody negative at all post-baseline visits). | Months 6, 12 | 
| Height Standard Deviation Score (SDS) at Months 6 and 12 (Change From Baseline) | Height Standard Deviation Score (SDS) allows for the comparison of a participants height to that of others in the same age group. Therefore, the average height for that age group will have the SDS of 0. In this study, the starting Height SDS score was ≤ -1.5 (≤ 5th percentile). Results are presented according to anti-GH antibody status (positive included all participants that were anti-GH antibody positive at least once post-baseline visit and anti-GH antibody negative population included all participants that were anti-GH antibody negative at all post-baseline visits. | Months 6, 12 | 
| Percentage of Participants With Adverse Events | Among participants who received at least one dose of study drug, those who reported at least one adverse event during study participation. | Baseline up to 1 year |