Mucopolysaccharidosis I, Mucopolysaccharidosis II, Mucopolysaccharidosis VI
Conditions
Keywords
MPS I, MPS II, MPS VI, growth hormone, short stature
Brief summary
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
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.
Interventions
DRUGSomatropin (DNA origin)
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.
Sponsors
Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
5 Years to 17 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in Growth Velocity From Baseline to End of Study Year 1. | 12 months |
Secondary
| Measure | Time frame |
|---|---|
| Safety: Number Drug Related SAEs | 1 months |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Growth Hormone Treatmen Growth hormone treatment arm. Somatropin (DNA origin)
Somatropin (DNA origin): 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. | 1 |
| No Growth Hormone Treatment in Year 1 No growth hormone treatment in year 1; option for treatment in year 2 open-label period. | 1 |
| Total | 2 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Growth Hormone Treatmen | No Growth Hormone Treatment in Year 1 | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 1 Participants | 1 Participants | 2 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 10.9 years | 13.5 years | 12.2 years |
| Region of Enrollment United States | 1 participants | 1 participants | 2 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 1 Participants | 1 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 1 / 1 | 0 / 0 |
| serious Total, serious adverse events | 0 / 1 | 0 / 0 |
Outcome results
Primary
Change in Growth Velocity From Baseline to End of Study Year 1.
Time frame: 12 months
Population: Zero participants analyzed in the No growth hormone treatment group due to subject withdrew from study as soon as informed they were assigned the no treatment group.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Growth Hormone Treatment | Change in Growth Velocity From Baseline to End of Study Year 1. | NA cm/yr |
Secondary
Safety: Number Drug Related SAEs
Time frame: 1 months
Population: Study stopped early due to inability to enroll participants.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Growth Hormone Treatment | Safety: Number Drug Related SAEs | 0 Participants |
| No Growth Hormone Treatment | Safety: Number Drug Related SAEs | 0 Participants |