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

Condition(s) targeted: Mucopolysaccharidosis I; Mucopolysaccharidosis II; Mucopolysaccharidosis VI

Intervention: Somatropin (DNA origin) (Drug)

Phase: Phase 2/Phase 3

Status: Terminated

Sponsored by: Los Angeles Biomedical Research Institute

Official(s) and/or principal investigator(s):
Lynda E Polgreen, M.D., Principal Investigator, Affiliation: University of Minnesota - Clinical and Translational Science Institute

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.

Official title: 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

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Change in Growth Velocity From Baseline to End of Study Year 1.

Secondary outcome:

Safety of Nutropin AQ® in Children With MPS I, II, and VI. Safety Endpoints Are: • Physical Examinations • Fundoscopic Examinations • Adverse Events • Radiographic Examinations of Spine and Lower Extremities

Change in Bone Mineral Density, Content, and Strength by DXA and pQCT, and Change in Serum Markers of Bone Metabolism.

Change in Mobility Measured by Force and Gait Measurements.

Change in Muscle Strength Measured by Biodex and Hand Grip Dynamometer.

Change in Neuropsychological Functioning and Brain Volumetrics.

Detailed description: 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.

Minimum age: 5 Years. Maximum age: 17 Years. Gender(s): Both.

Criteria:

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

University of Minnesota, Minneapolis, Minnesota 55455, United States

Starting date: November 2008
Last updated: November 19, 2014