Maroteaux-Lamy Syndrome, Mucopolysaccharidosis VI
Conditions
Brief summary
The purpose of the study is to evaluate the safety and efficacy of two dose levels of Naglazyme in infants under the age of one year who have MPS VI by monitoring physical appearance, x-ray of the skeletal system and growth.
Detailed description
The primary objective of the study was to evaluate the efficacy of two dose levels of Naglazyme in preventing the progression of skeletal dysplasia in infants under the age of one year who have MPS VI by monitoring physical appearance, x-ray of the skeletal system and growth. The secondary objective of the study was to evaluate the efficacy of the two dose levels of Naglazyme in preventing several measures of disease progression in infants under the age of one year who have MPS VI by monitoring urinary GAGs, gross and fine motor function, cardiac function, vision, hearing, and use of health resources. The safety objective of the study was to evaluate the safety of two dose levels of Naglazyme in infants under the age of one year who have MPS VI.
Interventions
DRUGNaglazyme
Weekly infusion for minimum of 52 weeks. Naglazyme is diluted in sterile 0.9% sodium chloride solution
Sponsors
BioMarin Pharmaceutical
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 1 Years
Healthy volunteers
No
Inclusion criteria
* Signed informed consent by a parent or legal guardian * Parent or legal guardian willing and able to comply with all study procedures * Equal to or greater than 36 weeks estimated gestational age by physical exam at birth * Has a diagnosis of MPS VI based on a documented prenatal diagnosis or fibroblast or leukocyte N-acetylgalactosamine 4-sulfatase (ASB) enzyme activity level of less than 10% of the lower limit of the normal range of the measuring laboratory * Is less than one year of age * Has no evidence of skeletal dysplasia based on physical exam
Exclusion criteria
* Parent of legal guardian perceived to be unreliable or unavailable for study participation * Use of any investigational drug within 30 days prior to screening, or requirement for any investigational agent prior to completion of all scheduled study assessments * Has concurrent disease or condition that would interfere with study participation or safety (i.e., has previously undergone hematopoietic stem cell transplantation such as bone marrow or cord blood transplantation, or major organ transplantation) * Any condition that, in the view of the principle investigator, renders the subject at high risk from treatment compliance and/or completing the study * Has known hypersensitivity to Naglazyme * Has previously received Naglazyme
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in Height | 52 weeks |
| Change in Weight | 52 weeks |
| Change in Haed Circumference | 52 weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Urinary Glycosaminoglycan Levels | minimum 52 weeks of dosing | Change in urinary GAG levels was calculated from baseline to week 52 of treatment. |
Countries
France, Portugal, United States
Participant flow
Recruitment details
Global study sites were hospitals. First Enrollment: 08MAY2006 Last Dose: 30APR2009
Participants by arm
| Arm | Count |
|---|---|
| Naglazyme, 1.0 mg/kg weekly infusions for minimum of 52 weeks | 2 |
| Naglazyme, 2.0 mg/kg weekly infusions for minimum of 52 weeks | 2 |
| Total | 4 |
Baseline characteristics
| Characteristic | Naglazyme, 1.0 mg/kg | Naglazyme, 2.0 mg/kg | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 2 Participants | 2 Participants | 4 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 | 6.05 months STANDARD_DEVIATION 3.89 | 12.4 months STANDARD_DEVIATION 0.42 | 9.23 months STANDARD_DEVIATION 4.31 |
| Race/Ethnicity, Customized Hispanic/Latino | 1 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized Other | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized White, non-Hispanic | 1 participants | 1 participants | 2 participants |
| Region of Enrollment France | 0 participants | 1 participants | 1 participants |
| Region of Enrollment Portugal | 0 participants | 1 participants | 1 participants |
| Region of Enrollment United States | 2 participants | 0 participants | 2 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 2 Participants | 2 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 2 / 2 | 2 / 2 |
| serious Total, serious adverse events | 2 / 2 | 2 / 2 |
Outcome results
Primary
Change in Haed Circumference
Time frame: 52 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Naglazyme, 1.0 mg/kg | Change in Haed Circumference | head circumference at baseline | 43.5 centimeter | Standard Deviation 3 |
| Naglazyme, 1.0 mg/kg | Change in Haed Circumference | head circumference at 52 weeks | 48.5 centimeter | Standard Deviation 1 |
| Naglazyme, 1.0 mg/kg | Change in Haed Circumference | Change in head circumference | 5.0 centimeter | Standard Deviation 4 |
| Naglazyme, 2.0 mg/kg | Change in Haed Circumference | Change in head circumference | 2.7 centimeter | Standard Deviation 1.3 |
| Naglazyme, 2.0 mg/kg | Change in Haed Circumference | head circumference at baseline | 49.1 centimeter | Standard Deviation 0.5 |
| Naglazyme, 2.0 mg/kg | Change in Haed Circumference | head circumference at 52 weeks | 51.8 centimeter | Standard Deviation 0.8 |
Primary
Change in Height
Time frame: 52 weeks
Population: Intention to treat.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Naglazyme, 1.0 mg/kg | Change in Height | Height at baseline | 67.3 centimeters | Standard Deviation 5.1 |
| Naglazyme, 1.0 mg/kg | Change in Height | Height at week 52 | 81.9 centimeters | Standard Deviation 1.8 |
| Naglazyme, 1.0 mg/kg | Change in Height | Change in height | 14.6 centimeters | Standard Deviation 6.9 |
| Naglazyme, 2.0 mg/kg | Change in Height | Height at baseline | 80.3 centimeters | Standard Deviation 1.8 |
| Naglazyme, 2.0 mg/kg | Change in Height | Height at week 52 | 91.3 centimeters | Standard Deviation 5.2 |
| Naglazyme, 2.0 mg/kg | Change in Height | Change in height | 11.0 centimeters | Standard Deviation 7 |
Primary
Change in Weight
Time frame: 52 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Naglazyme, 1.0 mg/kg | Change in Weight | weight at baseline | 7.1 kilograms | Standard Deviation 0.3 |
| Naglazyme, 1.0 mg/kg | Change in Weight | weight at week 52 | 11.3 kilograms | Standard Deviation 0.3 |
| Naglazyme, 1.0 mg/kg | Change in Weight | change in weight | 4.2 kilograms | Standard Deviation 0.6 |
| Naglazyme, 2.0 mg/kg | Change in Weight | weight at baseline | 10.2 kilograms | Standard Deviation 0.6 |
| Naglazyme, 2.0 mg/kg | Change in Weight | weight at week 52 | 13.3 kilograms | Standard Deviation 1 |
| Naglazyme, 2.0 mg/kg | Change in Weight | change in weight | 3.1 kilograms | Standard Deviation 1.6 |
Secondary
Change in Urinary Glycosaminoglycan Levels
Change in urinary GAG levels was calculated from baseline to week 52 of treatment.
Time frame: minimum 52 weeks of dosing
Population: Intention to treat.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Naglazyme, 1.0 mg/kg | Change in Urinary Glycosaminoglycan Levels | Baseline | 1041.87 ug/mg creatinine | Standard Deviation 86.32 |
| Naglazyme, 1.0 mg/kg | Change in Urinary Glycosaminoglycan Levels | Week 52 | 261.15 ug/mg creatinine | Standard Deviation 54.38 |
| Naglazyme, 1.0 mg/kg | Change in Urinary Glycosaminoglycan Levels | Change from Baseline to Week 52 | -780.72 ug/mg creatinine | Standard Deviation 140.69 |
| Naglazyme, 2.0 mg/kg | Change in Urinary Glycosaminoglycan Levels | Baseline | 698.95 ug/mg creatinine | Standard Deviation 142.34 |
| Naglazyme, 2.0 mg/kg | Change in Urinary Glycosaminoglycan Levels | Week 52 | 178.10 ug/mg creatinine | Standard Deviation 42.43 |
| Naglazyme, 2.0 mg/kg | Change in Urinary Glycosaminoglycan Levels | Change from Baseline to Week 52 | -520.85 ug/mg creatinine | Standard Deviation 99.91 |