Mucopolysaccharidosis VI
Conditions
Brief summary
The purpose of the study is to evaluate the ability of rhASB versus placebo to enhance endurance in patients with Mucopolysaccharidosis VI (MPS VI), as evidenced by an increase in the number of meters walked in the 12 minute walk test at Week 24 compared with baseline.
Interventions
DRUGPlacebo
Sponsors
BioMarin Pharmaceutical
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE
Eligibility
Sex/Gender
ALL
Age
7 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patient consent * Patient must be seven years of age or older * Patient must have documented biochemical or genetic proof of MPS VI * The patient must be able to walk independently at least 5 meters and no more than 270 meters in the first 6 minutes, or no more then 400 meters total in 12 minutes, in the screening 12-minute walk test * If female of childbearing potential, patient must have a negative pregnancy test
Exclusion criteria
* Patient is under consideration for or has undergone a successful bone marrow transplant (BMT) * Patient refuses or is unable to complete all screening evaluations * Pregnant or lactating patient * Patient has received an investigational drug within 30 days prior to study enrollment * Patient has been previously treated with rhASB * Patient has a medical condition, serious intercurrent illness, or other extenuating circumstance that may significantly confound study results or decrease study compliance * The patient has clinically significant spinal cord compression * The patient has known hypersensitivity to rhASB or to components of the active or placebo test solutions
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in 12-minute Walk Test at 24 Weeks | baseline and 24 weeks | Number of meters walked in 12 minutes at week 24 minus number of meters walked in 12 minutes at baseline |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in 3-minute Stair Climb at 24 Weeks | baseline and 24 weeks | Number of stairs climbed per minute in 3 minutes at 24 weeks minus number of stairs climbed per minute in 3 minutes at baseline |
| Change From Baseline in Urinary GAG (uGAG) at 24 Weeks | baseline and 24 weeks | Glycosaminoglycan (GAG) level measured in urine |
Countries
United States
Participant flow
Recruitment details
Study Locations:Oakland, CA, USA Mainz, Germany Manchester, England Porto Alegre, Brazil Lyon, France Porto, Portugal Study Duration: 24 weeks First enrollment: 21 July 2003 Last Dose Given: 1 April 2004 Last Assessment: 8 April 2004
Participants by arm
| Arm | Count |
|---|---|
| rhASB Intravenous (IV) recombinant human arylsulfatase(rhASB) at 1.0 mg/kg | 19 |
| Placebo Intravenous (IV) placebo solution at a volume equivalent to that needed for a 1.0 mg/kg dose of rhASB | 20 |
| Total | 39 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Total | rhASB | Placebo |
|---|---|---|---|
| Age Continuous | 12.2 years STANDARD_DEVIATION 5.62 | 13.7 years STANDARD_DEVIATION 6.47 | 10.7 years STANDARD_DEVIATION 4.35 |
| Race/Ethnicity, Customized Asian | 2 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized Black | 3 participants | 1 participants | 2 participants |
| Race/Ethnicity, Customized Hispanic | 4 participants | 1 participants | 3 participants |
| Race/Ethnicity, Customized Indigenous | 2 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized Other | 4 participants | 0 participants | 4 participants |
| Race/Ethnicity, Customized White, non-Hispanic | 24 participants | 15 participants | 9 participants |
| Region of Enrollment Brazil | 8 participants | 4 participants | 4 participants |
| Region of Enrollment France | 5 participants | 2 participants | 3 participants |
| Region of Enrollment Germany | 8 participants | 4 participants | 4 participants |
| Region of Enrollment Portugal | 6 participants | 4 participants | 2 participants |
| Region of Enrollment United Kingdom | 6 participants | 3 participants | 3 participants |
| Region of Enrollment United States | 6 participants | 2 participants | 4 participants |
| Sex: Female, Male Female | 26 Participants | 12 Participants | 14 Participants |
| Sex: Female, Male Male | 13 Participants | 7 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 19 / 19 | 20 / 20 |
| serious Total, serious adverse events | 3 / 19 | 4 / 20 |
Outcome results
Primary
Change From Baseline in 12-minute Walk Test at 24 Weeks
Number of meters walked in 12 minutes at week 24 minus number of meters walked in 12 minutes at baseline
Time frame: baseline and 24 weeks
Population: The efficacy analysis included all subjects except one from the placebo group who withdrew from the study prior to the week 24 assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| rhASB | Change From Baseline in 12-minute Walk Test at 24 Weeks | 109 meters | Standard Deviation 154 |
| Placebo | Change From Baseline in 12-minute Walk Test at 24 Weeks | 26 meters | Standard Deviation 122 |
p-value: 0.02595% CI: [11, 172]Regression, Linear
Secondary
Change From Baseline in 3-minute Stair Climb at 24 Weeks
Number of stairs climbed per minute in 3 minutes at 24 weeks minus number of stairs climbed per minute in 3 minutes at baseline
Time frame: baseline and 24 weeks
Population: The efficacy analysis included all subjects except one from the placbo group who withdrew from the study prior to the week 24 assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| rhASB | Change From Baseline in 3-minute Stair Climb at 24 Weeks | 7.4 stairs/min | Standard Deviation 9.9 |
| Placebo | Change From Baseline in 3-minute Stair Climb at 24 Weeks | 2.7 stairs/min | Standard Deviation 6.9 |
p-value: 0.05395% CI: [-0.1, 11.5]Regression, Linear
Secondary
Change From Baseline in Urinary GAG (uGAG) at 24 Weeks
Glycosaminoglycan (GAG) level measured in urine
Time frame: baseline and 24 weeks
Population: Baseline uGAG level was measured for 19 rhASB-treated subjects and 20 placebo-treated subjects. However, uGAG levels at 24 weeks were measured for 19 rhASB-treated subjects and 19 placebo-treated subjects, because 1 placebo-treated subject withdrew from the study before week 24.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| rhASB | Change From Baseline in Urinary GAG (uGAG) at 24 Weeks | Baseline Urinary GAG Level | 346 micrograms per mg creatinine | Standard Deviation 128 |
| rhASB | Change From Baseline in Urinary GAG (uGAG) at 24 Weeks | 24-week Urinary GAG Level | 85 micrograms per mg creatinine | Standard Deviation 35 |
| Placebo | Change From Baseline in Urinary GAG (uGAG) at 24 Weeks | Baseline Urinary GAG Level | 330 micrograms per mg creatinine | Standard Deviation 114 |
| Placebo | Change From Baseline in Urinary GAG (uGAG) at 24 Weeks | 24-week Urinary GAG Level | 317 micrograms per mg creatinine | Standard Deviation 80 |