Morquio A Syndrome, MPS IVA, Mucopolysaccharidosis IVA
Conditions
Keywords
Mucopolysaccharidosis IVA type A, MPS IVA Type A, Mucopolysaccharidosis IVA, MPS IVA, Morquio A Syndrome, Lysosomal Storage Disorder, LSD, N-acetylgalactosamine-6-sulfatase, N-acetylgalactosamine-6-sulfate, sulfatase, galactose-6-sulfatase, GALNS, enzyme replacement therapy, ERT
Brief summary
This open-label Phase 2 study will evaluate the safety and efficacy of weekly 2.0 mg/kg/wk infusions of BMN 110 in pediatric patients, less than 5 years of age at the time of administration of the first dose of study drug, diagnosed with MPS IVA (Morquio A Syndrome) for up to 208 weeks.
Interventions
DRUGBMN 110
Patients will receive intravenous (IV) infusions of study drug at a dose of 2.0 mg/kg/wk over a period of approximately 4 hours every week for up to 208 weeks.
Sponsors
BioMarin Pharmaceutical
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 5 Years
Healthy volunteers
No
Inclusion criteria
* Less than 5 years of age at the time of the first study drug infusion * Documented clinical diagnosis of MPS IVA based on clinical signs and symptoms of MPS IVA and documented reduced fibroblast or leukocyte GALNS enzyme activity or genetic testing confirming diagnosis of MPS IVA * Written informed consent provided by parent or legally authorized representative after the nature of the study has been explained and prior to any research-related procedures.
Exclusion criteria
* Previous hematopoietic stem cell transplant (HSCT). * Previous treatment with BMN 110. * Known hypersensitivity to any of the components of BMN 110. * Major surgery within 3 months prior to stuy entry or planned major surgery during the 52-week treatment period. * Use of any investigational product or investigational medical device within 30 days prior to Screening, or requirement for any investigational agent prior to completion of all scheduled study assessments. * Concurrent disease or condition, including but not limited to symptomatic cervical spine instability, clinically significant spinal cord compression, or severe cardiac disease that would interfere with study participation or safety as determined by the Investigator. * Any condition that, in the view of the Investigator, places the subject at high risk of poor treatment compliance or of not completing the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To Evaluate Safety and Tolerability of Infusions of BMN 110 at a Dose of 2.0 mg/kg/Week Over a 52-week Period in MPS IVA Subjects Less Than 5 Years of Age at Time of First Study Drug Infusion | 52 weeks | Number of Participants Experiencing Adverse Events |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline to Week 52 in Urinary Keratan Sulfate Measures | Baseline to Week 52 | Percent Change from Baseline to Week 52 for Urinary Keratan Sulfate measures. |
| Change From Baseline in Normalized Growth Rate Z-Scores | Baseline to Week 52 | Changes in growth over time will be assessed using anthropometric measurements and radiographs of lower extremities. Z-scores are the normalized scores derived from the reference population mean and standard deviation (A positive change from baseline indicates that the population has moved closer to the reference population and represents a positive outcome). |
Countries
Italy, Taiwan, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| BMN110 2.0 mg/kg/Week 2.0 mg/kg/week | 15 |
| Total | 15 |
Baseline characteristics
| Characteristic | BMN110 2.0 mg/kg/Week |
|---|---|
| Age, Continuous | 3.1 years STANDARD_DEVIATION 1.34 |
| Age, Customized 0 to <3 years | 7 participants |
| Age, Customized >=3 to <5 years | 8 participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 14 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race/Ethnicity, Customized Asian | 4 participants |
| Race/Ethnicity, Customized Other | 1 participants |
| Race/Ethnicity, Customized White | 10 participants |
| Region of Enrollment Italy | 2 participants |
| Region of Enrollment United Kingdom | 6 participants |
| Region of Enrollment United States | 7 participants |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 7 Participants |
| Urinary Keratan Sulfate Measures | 35.9 ug/mg STANDARD_DEVIATION 12.32 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 15 / 15 |
| serious Total, serious adverse events | 8 / 15 |
Outcome results
Primary
To Evaluate Safety and Tolerability of Infusions of BMN 110 at a Dose of 2.0 mg/kg/Week Over a 52-week Period in MPS IVA Subjects Less Than 5 Years of Age at Time of First Study Drug Infusion
Number of Participants Experiencing Adverse Events
Time frame: 52 weeks
Population: Safety Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| BMN110 2.0 mg/kg/Week | To Evaluate Safety and Tolerability of Infusions of BMN 110 at a Dose of 2.0 mg/kg/Week Over a 52-week Period in MPS IVA Subjects Less Than 5 Years of Age at Time of First Study Drug Infusion | 15 Participants |
Secondary
Change From Baseline in Normalized Growth Rate Z-Scores
Changes in growth over time will be assessed using anthropometric measurements and radiographs of lower extremities. Z-scores are the normalized scores derived from the reference population mean and standard deviation (A positive change from baseline indicates that the population has moved closer to the reference population and represents a positive outcome).
Time frame: Baseline to Week 52
Population: Efficacy analysis set - All enrolled patients with at least 1 post treatment efficacy measurement will be included in efficacy analyses.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BMN110 2.0 mg/kg/Week | Change From Baseline in Normalized Growth Rate Z-Scores | Baseline | -0.6 z-score | Standard Deviation 0.64 |
| BMN110 2.0 mg/kg/Week | Change From Baseline in Normalized Growth Rate Z-Scores | Change from Baseline to Week 52 | 0.2 z-score | Standard Deviation 1.04 |
Secondary
Percent Change From Baseline to Week 52 in Urinary Keratan Sulfate Measures
Percent Change from Baseline to Week 52 for Urinary Keratan Sulfate measures.
Time frame: Baseline to Week 52
Population: Efficacy Analysis Set - All enrolled patients with at least 1 post treatment efficacy measurement will be included in efficacy analyses.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BMN110 2.0 mg/kg/Week | Percent Change From Baseline to Week 52 in Urinary Keratan Sulfate Measures | -44.3 percentage change | Standard Deviation 21.15 |