Study of Weekly ALTU-238 Compared With Daily Nutropin AQ in Prepubertal Children With Growth Hormone Deficiency

Study Overview
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Brief Summary
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The purpose of the study is to evaluate the safety and effectiveness of ALTU-238 in the treatment of children with growth hormone deficiency who have not yet reached puberty who lack the normal ability to make growth hormone themselves. This study will also test if ALTU-238 works as a weekly treatment.

Official Title
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A Twelve Month, Phase II, Randomized, Open-Label, Multi-Center, Dose-Ranging Study of Weekly ALTU-238 (Somatropin) as Compared With Daily Nutropin AQ (Somatropin) in Prepubertal Children With Growth Hormone Deficiency

Conditions
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Growth Hormone Deficiency

Intervention / Treatment
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* Drug: Somatropin
* Drug: Somatropin
* Drug: Somatropin
* Drug: Somatropin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Assent of subject, if applicable, and written informed consent of parent or legal guardian Diagnosis of GHD as defined by a maximum stimulated GH < 7 ng/mL (μg/L) on two stimulation tests (using any two distinct agents from the following list: arginine, L-dopa, clonidine, insulin, or glucagon); if two documented historical tests are not available,test(s) must be performed during Screening period Available results from one or more historical CT or MRI scans of the head obtained at or following the diagnosis of GHD Chronologic age at Screening of 3 to 13 years (inclusive) for boys and 3 to 12 years(inclusive) for girls Bone age at Screening of ≤ 11 years for boys and ≤ 10 years for girls Pre-pubertal at Screening (Tanner stage 1 for both breast/genitalia and pubic hair For subjects with idiopathic GHD, a Screening height SDS ≤ -2.0 (standardized for chronologic age and sex) there is no height SDS requirement if the subject has organic GHD (as defined by a CNS lesion or insult on a historical CT or MRI scan) Pre-treatment annualized height velocity ≤ median (50th percentile) for chronologic age and sex (based on values for delayed maturers provided in Appendix 4), utilizing Screening height and height obtained 52 ± 13 weeks (i.e. 39 to 65 weeks) prior to Screening Screening IGF-1 SDS for chronologic age and sex < -1 If on thyroid hormone replacement therapy, the dose must be stable for at least 6 weeks prior to Screening and the free thyroxine level (T4), TSH, and cortisol must be within the normal range at the Screening visit Exclusion Criteria: History of any prior rhGH, rhIGF-1, or sex steroid treatment History of treatment with any medications that may affect growth Evidence of active intracranial neoplasm per recent serial CT or MRI scans of the head or other criteria Surgery/chemotherapy/radiation therapy for intracranial neoplasm within the prior 52 weeks Any history of non-intracranial neoplasm History of or active benign intracranial hypertension High-dose chronic systemic corticosteroid treatment (oral or injected) within prior 13 weeks Acute or severe illness within prior 26 weeks History of diabetes mellitus, anorexia nervosa, cystic fibrosis, chronic severe kidney or liver disease, chronic infectious disease, inborn errors of metabolism, chromosomal disorders, intrauterine growth retardation, or other childhood disease associated with growth failure History of congenital syndromes associated with abnormal growth, including Turner syndrome, Noonan syndrome, Prader-Willi syndrome, etc. History of severe associated pathology affecting growth, including malnutrition,malabsorption, or bone dysplasia History of autoimmune disease Serum ALT or AST ≥ 1.5X ULN Participation in another clinical trial or treatment with any investigational agent (drug or biologic) within 30 days prior to Baseline if the half-life of the agent is known to be ≤ 6 days or within 6 weeks prior to Baseline if the half-life is > 6 days or not known History of any allergic or abnormal reaction to any of the components of the study drugs Any previous or ongoing clinically significant illness, PE findings, or laboratory abnormality that, in the opinion of the Investigator or the Medical Monitor, could prevent the subject from completing the protocol-specified requirements successfully Poor likelihood, in the Investigator's opinion, that the subject will comply with protocol requirements (e.g., uncooperative attitude, inability to return for follow-up visits, history of medical noncompliance) and/or poor likelihood of completing the study

Ages Eligible for Study
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Minimum Age: 3 Years
Maximum Age: 13 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>ALTU-238 | Drug: Somatropin<br>* ALTU-238 0.3 mg/kg daily<br>|
| Experimental: 2<br>ALTU-238 | Drug: Somatropin<br>* ALTU-238 0.6 mg/kg daily<br>|
| Experimental: 3<br>ALTU-238 | Drug: Somatropin<br>* ALTU-238 0.9 mg/kg daily<br>|
| Active Comparator: 4<br>Nutropin AQ | Drug: Somatropin<br>* Nutropin AQ 0.043 mg/kg daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean change in annualized height velocity from pre-treatment to the first 26 weeks of treatment |  | 26 Weeks |