Clinical Trial of Growth Hormone in MPS I, II, and VI

Study Overview
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Brief Summary
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The purpose of this study is to determine whether growth hormone is a safe and effective treatment for short stature in children with Mucopolysaccharidosis type I, II, and VI.

Detailed Description
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Although children with MPS I, II, and VI who are treated with Hematopoietic Cell Transplantation (HCT) and/or enzyme replacement therapy (ERT) are living into adulthood with good cognitive development, their quality of life is significantly impacted by their skeletal abnormalities (i.e., kyphosis, scoliosis, and genu valgum), contractures, and severe short stature. Here at the University of Minnesota we have seen some promising clinical outcomes in children with MPS IH whom we have treated with human growth hormone (hGH). There are currently no reports in the literature of the impact of treating children with MPS and short stature, with hGH on their growth velocity or characteristic skeletal abnormalities. This study will advance the care of these children by providing data in this yet unexplored area of pediatric medicine with the goal of improving the quality of life for these children by improving height, mobility, and neuropsychological functioning. This is a Phase II/III randomized, single-center, 12 month clinical trial of growth hormone in male and female participants with MPS I, II, or VI, followed by 12 months open label. Participants with height ≤ -2 SDS for age and gender will be randomized for the first 12 months 1:1 to treatment or no treatment. At the conclusion of the 12 months, all subjects will be offered an additional 12 months of treatment.

Official Title
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Phase II/III, Randomized, Clinical Trial of the Effects of Nutropin AQ® on Growth and Bone Metabolism in Children With MPS I, II, and VI and Short Stature

Conditions
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Mucopolysaccharidosis I, Mucopolysaccharidosis II, Mucopolysaccharidosis VI

Intervention / Treatment
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* Drug: Somatropin (DNA origin)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A parent or legally authorized representative must provide written informed consent and comply with study assessments for the full duration of the study. Chronologic age ≥ 5 years and bone age ≤12 years Diagnosis of MPS I, II, or VI Height ≤ -2 SDS for age and gender Ability to travel to study center for evaluations. Ability of the participant to cooperate with study procedures, to notify a guardian of symptoms, and provide assent for participation in the study. Exclusion Criteria: History of treatment with hGH Untreated pituitary deficiency Pregnancy (positive urine pregnancy test) prior to enrollment in the study Participation in another simultaneous medical intervention trial Patients with closed epiphysis Active neoplasm Orthopedic procedure of the femur within the last 6 months. Known or suspected allergy to trial product or related products. Structural lesion on brain MRI resulting in brain compression Any other social or medical condition that the investigator believes would pose a significant hazard to the subject if the investigational therapy were initiated or be detrimental to the study. Obstructive sleep apnea without BiPAP or tonsillectomy/adenoidectomy treatment. CNS shunt. Abnormal cardiac function based on echocardiogram within 6 months prior to enrollment : Ejection fraction less than 50% Left ventricular chamber size greater than or less than 2 standard deviations of normal for body surface area Left ventricular wall thickness greater than or less than 2 standard deviations of normal for body surface area More than mild to moderate aortic insufficiency with abdominal aortic run-off More than mild to moderate mitral insufficiency with pulmonary hypertension Abnormal pulmonary function based on pulmonary function tests within 6 months prior to enrollment: abnormal FVC < 80% of predicted for age, gender, and height abnormal FEV1 < 80% predicted for age, gender, and height abnormal FEV1/FVC abnormal oxygen saturation

Ages Eligible for Study
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Minimum Age: 5 Years
Maximum Age: 17 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: Growth hormone treatmen<br>Growth hormone treatment arm. Somatropin (DNA origin) | Drug: Somatropin (DNA origin)<br>* The study starting dose of Nutropin AQ® will be 0.48 mg/kg/week divided into daily SC injections. Nutropin AQ® will be administered by either the subject or, if unable to demonstrate competency in this, then by the guardian. To decrease the risk of increased intracranial hypertension, the dose in the first month of treatment will be decreased by 50% (0.24 mg/kg/week), and then increased to 0.48 mg/kg/week if tolerated well after 1 month.<br>* Other names: Nutropin AQ;|
| No Intervention: No growth hormone treatment in year 1<br>No growth hormone treatment in year 1; option for treatment in year 2 open-label period. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Growth Velocity From Baseline to End of Study Year 1. |  | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety: Number Drug Related SAEs |  | 1 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MPS I, MPS II, MPS VI, growth hormone, short stature