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, MOR-006, CPET, Limited ambulation, Grip/ Pinch
Brief summary
The primary objective of this study is to evaluate the effect of 2.0 mg/kg/week BMN 110 in a patient population that has limited ambulation, in a period of up to 144 weeks.
Detailed description
Effect is defined by the following key domains: * Upper extremity function and dexterity * Mobility
Interventions
DRUGBMN 110
Drug will be delivered through a 4 hour (approximate) IV infusion at a dosage amount of 2.0 mg/kg/week for up to 144 weeks of treatment.
Sponsors
BioMarin Pharmaceutical
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
5 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Is willing and able to provide written, signed informed consent (or their legally authorized representative) after the nature of the study has been explained and prior to performance of any research-related procedure. Patients who do not meet country and local age requirements for informed consent must be willing and able to provide written assent after the nature of the study has been explained and prior to performance of any research-related procedure. * Has 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. * Is ≥ 5 years of age. * If sexually active, is willing to use an acceptable method of contraception while participating in the study. * Females of childbearing potential must have a negative pregnancy test at the Screening Visit and be willing to have additional pregnancy tests during the study. * Is willing and able to perform all study procedures as physically possible.
Exclusion criteria
* Is able to walk farther than a specified distance as assessed by the 6MWT. * Has previous hematopoietic stem cell transplant (HSCT). * Has received previous treatment with BMN 110. * Has a known hypersensitivity to any of the components of BMN 110. * Has had major surgery within 3 months prior to study entry or is planning to have a major surgery during the first 24 weeks of the study. * Has used any other investigational product or investigational medical device within 30 days prior to the Screening Visit or requires any investigational agent prior to completion of all scheduled study assessments. * Is pregnant or breastfeeding at the Screening Visit or planning to become pregnant (self or partner) at any time during the study. * Has a concurrent disease or condition, including but not limited to symptomatic cervical spine instability or severe cardiac disease or complete paralysis due to a spinal cord injury (defined as an inability to move arms and legs), that would interfere with study participation or safety as determined by the Investigator. * Has any condition that, in the view of the Investigator, places the patient at high risk of poor treatment compliance or of not completing the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Speed as Measured in Functional Dexterity Test (FDT) | Up to 96 weeks | FDT assesses the ability to use the hand in daily tasks. The test involves turning 16 wooden pegs over as quickly as possible on a hardwood pegboard with one hand requiring a three-jaw chuck prehension pattern between the fingers and thumb within a two-minute time limit. Hand function is evaluated by how fast a patient can turn over pegs in the given time limit, i.e. speed (number of pegs/minute). |
| Change From Baseline in Strength as Assessed by Grip and Pinch Test (GPT) | Up to 96 weeks | A grip-strength dynamometer and a pinch meter were used to measure grip strength and pinch strength. The results report change from baseline in strength for dominant and non-dominant hand in a forearm and wrist supported position. |
| Percent Change From Baseline in Speed as Measured in Timed 25-Foot Walk Test (25FWT) | Up to 96 weeks | The timed 25-Foot Walk Test (25FWT) is an assessment of mobility and performance of leg function. The patient was instructed to walk a marked 25-foot course as quickly as possible in a time limit of 3 minutes and immediately walk back the same distance when reaching one end.The patient is allowed to use any ambulation method to move. The outcome measures the speed (feet / min) of moving. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Normalized Urine Keratan Sulfate (uKS) | Up to 96 weeks | Urinary keratan sulfate and urinary creatinine were measured through quantitative analysis. uKS is normalized to creatinine. |
Countries
Germany, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| BMN 110 at 2.0 mg/kg/Week Weekly IV infusions of BMN 110 at 2.0 mg/kg/week over a period of approximately 4 hours per infusion for an initial treatment phase of 48 weeks and an extension treatment phase of up to an additional 96 weeks. | 16 |
| Total | 16 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Extension Phase | Terminated by Sponsor | 15 |
| Primary Phase | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | BMN 110 at 2.0 mg/kg/Week |
|---|---|
| Age, Continuous | 20.7 years STANDARD_DEVIATION 8.38 |
| Age, Customized 12 to 18 years | 8 participants |
| Age, Customized >=19 years | 7 participants |
| Age, Customized 5 to 11 years | 1 participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 12 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 participants |
| Race/Ethnicity, Customized Asian | 2 participants |
| Race/Ethnicity, Customized Black or African American | 1 participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 participants |
| Race/Ethnicity, Customized Other | 1 participants |
| Race/Ethnicity, Customized White | 12 participants |
| Region of Enrollment Germany | 6 participants |
| Region of Enrollment United Kingdom | 4 participants |
| Region of Enrollment United States | 6 participants |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 9 Participants |
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 | 7 / 15 |
Outcome results
Primary
Change From Baseline in Strength as Assessed by Grip and Pinch Test (GPT)
A grip-strength dynamometer and a pinch meter were used to measure grip strength and pinch strength. The results report change from baseline in strength for dominant and non-dominant hand in a forearm and wrist supported position.
Time frame: Up to 96 weeks
Population: Modified ITT Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BMN 110 at 2.0 mg/kg/Week | Change From Baseline in Strength as Assessed by Grip and Pinch Test (GPT) | Grip Dominant Hand Wk 24 Chg from Baseline | 0.1 kg | Standard Deviation 0.89 |
| BMN 110 at 2.0 mg/kg/Week | Change From Baseline in Strength as Assessed by Grip and Pinch Test (GPT) | Grip Dominant Hand Wk 72 Chg from Baseline | -0.1 kg | Standard Deviation 0.33 |
| BMN 110 at 2.0 mg/kg/Week | Change From Baseline in Strength as Assessed by Grip and Pinch Test (GPT) | Grip Dominant Hand Wk 96 Chg from Baseline | 0.3 kg | Standard Deviation 0.23 |
| BMN 110 at 2.0 mg/kg/Week | Change From Baseline in Strength as Assessed by Grip and Pinch Test (GPT) | Grip Non-Dominant Hand Wk24 Chg from Baseline | -0.0 kg | Standard Deviation 0.7 |
| BMN 110 at 2.0 mg/kg/Week | Change From Baseline in Strength as Assessed by Grip and Pinch Test (GPT) | Grip Non-Dominant Hand Wk 48 Chg from Baseline | -0.1 kg | Standard Deviation 0.66 |
| BMN 110 at 2.0 mg/kg/Week | Change From Baseline in Strength as Assessed by Grip and Pinch Test (GPT) | Grip Non-Dominant Hand Wk 72 Chg from Baseline | 0.1 kg | Standard Deviation 0.79 |
| BMN 110 at 2.0 mg/kg/Week | Change From Baseline in Strength as Assessed by Grip and Pinch Test (GPT) | Grip Non-Dominant Hand Wk 96 Chg from Baseline | 0.4 kg | Standard Deviation 0.87 |
| BMN 110 at 2.0 mg/kg/Week | Change From Baseline in Strength as Assessed by Grip and Pinch Test (GPT) | Pinch Dominant Hand Wk 24 Chg from Baseline | -0.1 kg | Standard Deviation 0.32 |
| BMN 110 at 2.0 mg/kg/Week | Change From Baseline in Strength as Assessed by Grip and Pinch Test (GPT) | Pinch Dominant Hand Wk 48 Chg from Baseline | -0.0 kg | Standard Deviation 0.3 |
| BMN 110 at 2.0 mg/kg/Week | Change From Baseline in Strength as Assessed by Grip and Pinch Test (GPT) | Pinch Dominant Hand Wk 72 Chg from Baseline | -0.1 kg | Standard Deviation 0.23 |
| BMN 110 at 2.0 mg/kg/Week | Change From Baseline in Strength as Assessed by Grip and Pinch Test (GPT) | Pinch Dominant Hand Wk 96 Chg from Baseline | -0.6 kg | — |
| BMN 110 at 2.0 mg/kg/Week | Change From Baseline in Strength as Assessed by Grip and Pinch Test (GPT) | Pinch Non-Dominant Hand Wk 24 Chg from Baseline | -0.0 kg | Standard Deviation 0.18 |
| BMN 110 at 2.0 mg/kg/Week | Change From Baseline in Strength as Assessed by Grip and Pinch Test (GPT) | Pinch Non-Dominant Hand Wk 48 Chg from Baseline | 0.0 kg | Standard Deviation 0.27 |
| BMN 110 at 2.0 mg/kg/Week | Change From Baseline in Strength as Assessed by Grip and Pinch Test (GPT) | Pinch Non-Dominant Hand Wk 72 Chg from Baseline | -0.1 kg | Standard Deviation 0.31 |
| BMN 110 at 2.0 mg/kg/Week | Change From Baseline in Strength as Assessed by Grip and Pinch Test (GPT) | Pinch Non-Dominant Hand Wk 96 Chg from Baseline | -0.3 kg | Standard Deviation 0.36 |
| BMN 110 at 2.0 mg/kg/Week | Change From Baseline in Strength as Assessed by Grip and Pinch Test (GPT) | Grip Dominant Hand Wk 48 Chg from Baseline | -0.3 kg | Standard Deviation 0.9 |
Primary
Percent Change From Baseline in Speed as Measured in Functional Dexterity Test (FDT)
FDT assesses the ability to use the hand in daily tasks. The test involves turning 16 wooden pegs over as quickly as possible on a hardwood pegboard with one hand requiring a three-jaw chuck prehension pattern between the fingers and thumb within a two-minute time limit. Hand function is evaluated by how fast a patient can turn over pegs in the given time limit, i.e. speed (number of pegs/minute).
Time frame: Up to 96 weeks
Population: Modified ITT Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BMN 110 at 2.0 mg/kg/Week | Percent Change From Baseline in Speed as Measured in Functional Dexterity Test (FDT) | Dominant Hand Wk 24 % Chg from Baseline | 1.8 % of change | Standard Deviation 45.6 |
| BMN 110 at 2.0 mg/kg/Week | Percent Change From Baseline in Speed as Measured in Functional Dexterity Test (FDT) | Dominant Hand Wk 48 % Chg from Baseline | 23.1 % of change | Standard Deviation 53.88 |
| BMN 110 at 2.0 mg/kg/Week | Percent Change From Baseline in Speed as Measured in Functional Dexterity Test (FDT) | Dominant Hand Wk 72 % Chg from Baseline | 37.2 % of change | Standard Deviation 54.94 |
| BMN 110 at 2.0 mg/kg/Week | Percent Change From Baseline in Speed as Measured in Functional Dexterity Test (FDT) | Dominant Hand Wk 96 % Chg from Baseline | 22.5 % of change | Standard Deviation 42.21 |
| BMN 110 at 2.0 mg/kg/Week | Percent Change From Baseline in Speed as Measured in Functional Dexterity Test (FDT) | Non-Dominant Hand Wk 24 % Chg from Baseline | 13.8 % of change | Standard Deviation 32.54 |
| BMN 110 at 2.0 mg/kg/Week | Percent Change From Baseline in Speed as Measured in Functional Dexterity Test (FDT) | Non-Dominant Hand Wk 48 % Chg from Baseline | 6.0 % of change | Standard Deviation 35.78 |
| BMN 110 at 2.0 mg/kg/Week | Percent Change From Baseline in Speed as Measured in Functional Dexterity Test (FDT) | Non-Dominant Hand Wk 72 % Chg from Baseline | 49.3 % of change | Standard Deviation 126.26 |
| BMN 110 at 2.0 mg/kg/Week | Percent Change From Baseline in Speed as Measured in Functional Dexterity Test (FDT) | Non-Dominant Hand Wk 96 % Chg from Baseline | -2.0 % of change | Standard Deviation 2.83 |
Primary
Percent Change From Baseline in Speed as Measured in Timed 25-Foot Walk Test (25FWT)
The timed 25-Foot Walk Test (25FWT) is an assessment of mobility and performance of leg function. The patient was instructed to walk a marked 25-foot course as quickly as possible in a time limit of 3 minutes and immediately walk back the same distance when reaching one end.The patient is allowed to use any ambulation method to move. The outcome measures the speed (feet / min) of moving.
Time frame: Up to 96 weeks
Population: Modified ITT Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BMN 110 at 2.0 mg/kg/Week | Percent Change From Baseline in Speed as Measured in Timed 25-Foot Walk Test (25FWT) | Wk 24 % Change from Baseline Two Attempts Combined | 95.7 % of change | Standard Deviation 142.37 |
| BMN 110 at 2.0 mg/kg/Week | Percent Change From Baseline in Speed as Measured in Timed 25-Foot Walk Test (25FWT) | Wk 48 % Change from Baseline Two Attempts Combined | 53.5 % of change | Standard Deviation 102.74 |
| BMN 110 at 2.0 mg/kg/Week | Percent Change From Baseline in Speed as Measured in Timed 25-Foot Walk Test (25FWT) | Wk 72 % Change from Baseline Two Attempts Combined | 48.3 % of change | Standard Deviation 145.01 |
| BMN 110 at 2.0 mg/kg/Week | Percent Change From Baseline in Speed as Measured in Timed 25-Foot Walk Test (25FWT) | Wk 96 % Change from Baseline Two Attempts Combined | NA % of change | — |
Secondary
Percent Change From Baseline in Normalized Urine Keratan Sulfate (uKS)
Urinary keratan sulfate and urinary creatinine were measured through quantitative analysis. uKS is normalized to creatinine.
Time frame: Up to 96 weeks
Population: Modified ITT Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BMN 110 at 2.0 mg/kg/Week | Percent Change From Baseline in Normalized Urine Keratan Sulfate (uKS) | Week 24 % Change from Baseline | -47.7 % of change | Standard Deviation 15.4 |
| BMN 110 at 2.0 mg/kg/Week | Percent Change From Baseline in Normalized Urine Keratan Sulfate (uKS) | Week 48 % Change from Baseline | -43.4 % of change | Standard Deviation 24.82 |
| BMN 110 at 2.0 mg/kg/Week | Percent Change From Baseline in Normalized Urine Keratan Sulfate (uKS) | Week 72 % Change from Baseline | -45.5 % of change | Standard Deviation 19.67 |
| BMN 110 at 2.0 mg/kg/Week | Percent Change From Baseline in Normalized Urine Keratan Sulfate (uKS) | Week 96 % Change from Baseline | -48.3 % of change | Standard Deviation 24.13 |