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

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.

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