Morquio A Syndrome, MPS IVA, Mucopolysaccharidosis IV A
Conditions
Keywords
Mucopolysaccharidosis IV type A, MPS IV 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 Phase 3 extension study will evaluate the long-term efficacy and safety of BMN 110 2.0 mg/kg/week and/or BMN 110 2.0 mg/kg/every other week in patients with mucopolysaccharidosis IVA (Morquio A Syndrome).
Detailed description
This is a multi-center, multinational, extension study to evaluate 2 dose regimens of BMN 110 treatment in patients with MPS IVA who completed MOR-004. The last study visit assessments for MOR-004 will constitute Baseline for this study. The first study drug dose of this protocol will occur on Week 0 of MOR-005, which is the same as the last visit (Week 24) of MOR-004. Initially, the study will be double-blind with patients previously randomized to BMN 110 in MOR-004 remaining on their assigned BMN 110 dose regimen (qw or qow dosing). The MOR-004 placebo patients will be re-randomized (1:1 ratio) to one of the 2 BMN 110 dose regimen groups: 2.0 mg/kg/qw or 2.0 mg/kg/qow. There will be two study parts: * Part 1 - randomized double-blind until the optimal BMN 110 dose regimen has been determined, based on the final primary efficacy analysis from MOR-004 * Part 2 - open-label BMN 110 treatment with the single optimal dose regimen
Interventions
DRUGBMN 110 - Weekly
In Part 1, patients will receive intravenous (IV) infusions of study drug at a dose of 2.0 mg/kg/qw administered over a period of approximately 4 hours once a week. In Part 2, patients will continue to receive 2.0 mg/kg of BMN 110 every week, with no placebo.
DRUGBMN 110 - Every Other Week
In Part 1, patients will receive intravenous (IV) infusions of study drug at a dose of 2.0 mg/kg administered over a period of approximately 4 hours every other week. Patients randomized to the 2.0 mg/kg/qow arm will receive infusions of placebo on alternating weeks, to mask active drug weeks. In Part 2, patients will receive 2.0 mg/kg of BMN 110 every week, with no placebo.
Sponsors
BioMarin Pharmaceutical
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
5 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Must have completed MOR-004 * Is willing and able to provide written, signed informed consent. Or in the case of patients under the age of 18 (or other age as defined by regional law or regulation), provide written assent (if required) and have written informed consent, signed by a legally authorize representative, after the nature of the study has been explained, and prior to performance of research-related procedures. * If sexually active, must be willing to use an acceptable method of contraception while participating in the study. * If female, of childbearing potential, must have a negative pregnancy test at Baseline and be willing to have additional pregnancy tests done during the study.
Exclusion criteria
* Is pregnant or breastfeeding, at Baseline, or planning to become pregnant (self or partner) at any time during the study. * Has used any investigational product (other than BMN 110 in MOR-004), or investigational medical device, within 30 days prior to Baseline; or is required to use any investigational agent prior to completion of all scheduled study assessments. * Was enrolled in a previous BMN 110 study, other than MOR-004. * Has a 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 pose a safety risk, 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 |
|---|---|---|
| Change From Baseline in 6-minute Walk (6MW) Test - ITT | Baseline to week 168 | Efficacy was assessed by changes from baseline in 6-minute walk test |
| Change From Baseline in 6-minute Walk (6MW) Test - MPP | Baseline to week 168 | Efficacy was assessed by changes from baseline in 6-minute walk test |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in 3-minute Stair Climb Test - ITT | Baseline to week 168 | Efficacy was assessed by changes from baseline in 3-minute stair climb test. |
| Change From Baseline in 3-minute Stair Climb Test - MPP | Baseline to week 168 | Efficacy was assessed by changes from baseline in 3-minute stair climb test. |
| Change From Baseline in Urine Keratan Sulfate - ITT | Baseline to week 168 | Efficacy was assessed by changes from baseline in urine keratan sulfate (normalized to urine creatinine.) |
| Change From Baseline in Urine Keratan Sulfate - MPP | Baseline to week 168 | Efficacy was assessed by changes from baseline in urine keratan sulfate (normalized to urine creatinine.) |
Countries
Argentina, Brazil, Canada, Colombia, Denmark, France, Germany, Italy, Japan, Netherlands, Norway, Portugal, Qatar, Saudi Arabia, South Korea, Spain, Taiwan, Turkey (Türkiye), United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| PBO-QOW Placebo in MOR004 + BMN110 2.0 mg/kg/qow in MOR005 | 29 |
| PBO-QW Placebo in MOR004 + BMN110 2.0 mg/kg/qw in MOR005 | 29 |
| QOW-QOW BMN110 2.0 mg/kg/qow in MOR004 + BMN110 2.0 mg/kg/qow in MOR005 | 59 |
| QW-QW BMN110 2.0 mg/kg/qw in MOR004 + BMN110 2.0 mg/kg/qw in MOR005 | 56 |
| Total | 173 |
Baseline characteristics
| Characteristic | PBO-QW | PBO-QOW | QOW-QOW | QW-QW | Total |
|---|---|---|---|---|---|
| Age, Continuous | 13.5 years STANDARD_DEVIATION 8.5 | 16.7 years STANDARD_DEVIATION 13.66 | 15.3 years STANDARD_DEVIATION 10.79 | 12.8 years STANDARD_DEVIATION 8.01 | 14.4 years STANDARD_DEVIATION 10.2 |
| Age, Customized 12 - 18 | 7 participants | 7 participants | 16 participants | 16 participants | 46 participants |
| Age, Customized >=19 | 7 participants | 7 participants | 12 participants | 8 participants | 34 participants |
| Age, Customized 5 - 11 | 15 participants | 15 participants | 31 participants | 32 participants | 93 participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 8 Participants | 4 Participants | 16 Participants | 9 Participants | 37 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 21 Participants | 25 Participants | 43 Participants | 47 Participants | 136 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants |
| Race/Ethnicity, Customized Asian | 7 participants | 4 participants | 15 participants | 14 participants | 40 participants |
| Race/Ethnicity, Customized Black or African American | 0 participants | 0 participants | 2 participants | 2 participants | 4 participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants |
| Race/Ethnicity, Customized Other | 4 participants | 0 participants | 7 participants | 5 participants | 16 participants |
| Race/Ethnicity, Customized White | 18 participants | 25 participants | 35 participants | 35 participants | 113 participants |
| Region of Enrollment Argentina | 1 participants | 0 participants | 1 participants | 0 participants | 2 participants |
| Region of Enrollment Brazil | 3 participants | 2 participants | 10 participants | 5 participants | 20 participants |
| Region of Enrollment Canada | 1 participants | 3 participants | 5 participants | 5 participants | 14 participants |
| Region of Enrollment Colombia | 2 participants | 0 participants | 2 participants | 2 participants | 6 participants |
| Region of Enrollment Denmark | 0 participants | 0 participants | 0 participants | 1 participants | 1 participants |
| Region of Enrollment France | 5 participants | 2 participants | 5 participants | 8 participants | 20 participants |
| Region of Enrollment Germany | 2 participants | 2 participants | 5 participants | 1 participants | 10 participants |
| Region of Enrollment Italy | 1 participants | 3 participants | 4 participants | 2 participants | 10 participants |
| Region of Enrollment Japan | 0 participants | 0 participants | 4 participants | 2 participants | 6 participants |
| Region of Enrollment Korea, South | 1 participants | 2 participants | 1 participants | 3 participants | 7 participants |
| Region of Enrollment Netherlands | 0 participants | 1 participants | 2 participants | 3 participants | 6 participants |
| Region of Enrollment Portugal | 1 participants | 1 participants | 1 participants | 0 participants | 3 participants |
| Region of Enrollment Qatar | 1 participants | 0 participants | 0 participants | 1 participants | 2 participants |
| Region of Enrollment Saudi Arabia | 2 participants | 0 participants | 1 participants | 4 participants | 7 participants |
| Region of Enrollment Taiwan | 1 participants | 0 participants | 3 participants | 1 participants | 5 participants |
| Region of Enrollment United Kingdom | 3 participants | 6 participants | 4 participants | 9 participants | 22 participants |
| Region of Enrollment United States | 5 participants | 7 participants | 11 participants | 9 participants | 32 participants |
| Sex: Female, Male Female | 18 Participants | 14 Participants | 25 Participants | 30 Participants | 87 Participants |
| Sex: Female, Male Male | 11 Participants | 15 Participants | 34 Participants | 26 Participants | 86 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 29 | 0 / 29 | 1 / 59 | 0 / 56 | 1 / 173 |
| other Total, other adverse events | 29 / 29 | 29 / 29 | 59 / 59 | 56 / 56 | 173 / 173 |
| serious Total, serious adverse events | 17 / 29 | 15 / 29 | 26 / 59 | 31 / 56 | 89 / 173 |
Outcome results
Primary
Change From Baseline in 6-minute Walk (6MW) Test - ITT
Efficacy was assessed by changes from baseline in 6-minute walk test
Time frame: Baseline to week 168
Population: ITT-intent-to-treat population, defined as all patients enrolled in the study who received patient IDs regardless of whether they received study drug or not.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PBO-QOW | Change From Baseline in 6-minute Walk (6MW) Test - ITT | Change from Baseline to Week 120 | 32.3 meters | Standard Deviation 92.13 |
| PBO-QOW | Change From Baseline in 6-minute Walk (6MW) Test - ITT | Baseline | 219.7 meters | Standard Deviation 74.22 |
| PBO-QOW | Change From Baseline in 6-minute Walk (6MW) Test - ITT | Change from Baseline to Week 168 | 52.2 meters | Standard Deviation 100.07 |
| PBO-QOW | Change From Baseline in 6-minute Walk (6MW) Test - ITT | Change from Baseline to Week 24 | 23.8 meters | Standard Deviation 56.21 |
| PBO-QOW | Change From Baseline in 6-minute Walk (6MW) Test - ITT | Change from Baseline to Week 72 | 41.5 meters | Standard Deviation 89.24 |
| PBO-QW | Change From Baseline in 6-minute Walk (6MW) Test - ITT | Change from Baseline to Week 120 | -2.9 meters | Standard Deviation 95.69 |
| PBO-QW | Change From Baseline in 6-minute Walk (6MW) Test - ITT | Change from Baseline to Week 72 | -1.5 meters | Standard Deviation 112.07 |
| PBO-QW | Change From Baseline in 6-minute Walk (6MW) Test - ITT | Change from Baseline to Week 24 | 5.0 meters | Standard Deviation 43.27 |
| PBO-QW | Change From Baseline in 6-minute Walk (6MW) Test - ITT | Change from Baseline to Week 168 | 20.1 meters | Standard Deviation 80.79 |
| PBO-QW | Change From Baseline in 6-minute Walk (6MW) Test - ITT | Baseline | 207.2 meters | Standard Deviation 64.87 |
| QOW-QOW | Change From Baseline in 6-minute Walk (6MW) Test - ITT | Change from Baseline to Week 72 | 27.2 meters | Standard Deviation 56.66 |
| QOW-QOW | Change From Baseline in 6-minute Walk (6MW) Test - ITT | Baseline | 205.7 meters | Standard Deviation 81.19 |
| QOW-QOW | Change From Baseline in 6-minute Walk (6MW) Test - ITT | Change from Baseline to Week 24 | 11.1 meters | Standard Deviation 49.95 |
| QOW-QOW | Change From Baseline in 6-minute Walk (6MW) Test - ITT | Change from Baseline to Week 120 | 6.0 meters | Standard Deviation 86.28 |
| QOW-QOW | Change From Baseline in 6-minute Walk (6MW) Test - ITT | Change from Baseline to Week 168 | 5.2 meters | Standard Deviation 81.54 |
| QW-QW | Change From Baseline in 6-minute Walk (6MW) Test - ITT | Change from Baseline to Week 168 | -8.8 meters | Standard Deviation 101.24 |
| QW-QW | Change From Baseline in 6-minute Walk (6MW) Test - ITT | Baseline | 203.9 meters | Standard Deviation 76.32 |
| QW-QW | Change From Baseline in 6-minute Walk (6MW) Test - ITT | Change from Baseline to Week 120 | 29.7 meters | Standard Deviation 81.37 |
| QW-QW | Change From Baseline in 6-minute Walk (6MW) Test - ITT | Change from Baseline to Week 72 | 30.6 meters | Standard Deviation 73.66 |
| QW-QW | Change From Baseline in 6-minute Walk (6MW) Test - ITT | Change from Baseline to Week 24 | 36.5 meters | Standard Deviation 58.49 |
| Total | Change From Baseline in 6-minute Walk (6MW) Test - ITT | Change from Baseline to Week 72 | 26.1 meters | Standard Deviation 79.26 |
| Total | Change From Baseline in 6-minute Walk (6MW) Test - ITT | Change from Baseline to Week 120 | 16.9 meters | Standard Deviation 87.67 |
| Total | Change From Baseline in 6-minute Walk (6MW) Test - ITT | Baseline | 207.2 meters | Standard Deviation 75.58 |
| Total | Change From Baseline in 6-minute Walk (6MW) Test - ITT | Change from Baseline to Week 168 | 8.9 meters | Standard Deviation 90.81 |
| Total | Change From Baseline in 6-minute Walk (6MW) Test - ITT | Change from Baseline to Week 24 | 20.2 meters | Standard Deviation 54.02 |
Primary
Change From Baseline in 6-minute Walk (6MW) Test - MPP
Efficacy was assessed by changes from baseline in 6-minute walk test
Time frame: Baseline to week 168
Population: MPP- modified per-protocol population, define as the ITT(intent to treat) after removing patients who had orthosurgery in first 120 weeks or \<96 doses in first 120 weeks.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PBO-QOW | Change From Baseline in 6-minute Walk (6MW) Test - MPP | Change from Baseline to Week 120 | 60.8 meters | Standard Deviation 64.45 |
| PBO-QOW | Change From Baseline in 6-minute Walk (6MW) Test - MPP | Baseline | 208.7 meters | Standard Deviation 78.12 |
| PBO-QOW | Change From Baseline in 6-minute Walk (6MW) Test - MPP | Change from Baseline to Week 168 | 85.8 meters | Standard Deviation 128.04 |
| PBO-QOW | Change From Baseline in 6-minute Walk (6MW) Test - MPP | Change from Baseline to Week 24 | 30.3 meters | Standard Deviation 56.53 |
| PBO-QOW | Change From Baseline in 6-minute Walk (6MW) Test - MPP | Change from Baseline to Week 72 | 54.5 meters | Standard Deviation 85.19 |
| PBO-QW | Change From Baseline in 6-minute Walk (6MW) Test - MPP | Change from Baseline to Week 120 | 19.8 meters | Standard Deviation 86.69 |
| PBO-QW | Change From Baseline in 6-minute Walk (6MW) Test - MPP | Change from Baseline to Week 72 | 37.7 meters | Standard Deviation 69.35 |
| PBO-QW | Change From Baseline in 6-minute Walk (6MW) Test - MPP | Change from Baseline to Week 24 | 9.6 meters | Standard Deviation 46.87 |
| PBO-QW | Change From Baseline in 6-minute Walk (6MW) Test - MPP | Change from Baseline to Week 168 | 14.6 meters | Standard Deviation 94.41 |
| PBO-QW | Change From Baseline in 6-minute Walk (6MW) Test - MPP | Baseline | 190.2 meters | Standard Deviation 65.54 |
| QOW-QOW | Change From Baseline in 6-minute Walk (6MW) Test - MPP | Change from Baseline to Week 72 | 35.3 meters | Standard Deviation 58.19 |
| QOW-QOW | Change From Baseline in 6-minute Walk (6MW) Test - MPP | Baseline | 195.9 meters | Standard Deviation 80.4 |
| QOW-QOW | Change From Baseline in 6-minute Walk (6MW) Test - MPP | Change from Baseline to Week 24 | 13.6 meters | Standard Deviation 52.65 |
| QOW-QOW | Change From Baseline in 6-minute Walk (6MW) Test - MPP | Change from Baseline to Week 120 | 19.7 meters | Standard Deviation 77.29 |
| QOW-QOW | Change From Baseline in 6-minute Walk (6MW) Test - MPP | Change from Baseline to Week 168 | 10.0 meters | Standard Deviation 84.66 |
| QW-QW | Change From Baseline in 6-minute Walk (6MW) Test - MPP | Change from Baseline to Week 168 | -12.3 meters | Standard Deviation 106.34 |
| QW-QW | Change From Baseline in 6-minute Walk (6MW) Test - MPP | Baseline | 208.8 meters | Standard Deviation 73.24 |
| QW-QW | Change From Baseline in 6-minute Walk (6MW) Test - MPP | Change from Baseline to Week 120 | 38.6 meters | Standard Deviation 66.65 |
| QW-QW | Change From Baseline in 6-minute Walk (6MW) Test - MPP | Change from Baseline to Week 72 | 37.5 meters | Standard Deviation 72.17 |
| QW-QW | Change From Baseline in 6-minute Walk (6MW) Test - MPP | Change from Baseline to Week 24 | 41.5 meters | Standard Deviation 59.89 |
| Total | Change From Baseline in 6-minute Walk (6MW) Test - MPP | Change from Baseline to Week 72 | 39.6 meters | Standard Deviation 69.11 |
| Total | Change From Baseline in 6-minute Walk (6MW) Test - MPP | Change from Baseline to Week 120 | 33.0 meters | Standard Deviation 73.94 |
| Total | Change From Baseline in 6-minute Walk (6MW) Test - MPP | Baseline | 201.6 meters | Standard Deviation 74.94 |
| Total | Change From Baseline in 6-minute Walk (6MW) Test - MPP | Change from Baseline to Week 168 | 8.8 meters | Standard Deviation 98.69 |
| Total | Change From Baseline in 6-minute Walk (6MW) Test - MPP | Change from Baseline to Week 24 | 25.4 meters | Standard Deviation 56.08 |
Secondary
Change From Baseline in 3-minute Stair Climb Test - ITT
Efficacy was assessed by changes from baseline in 3-minute stair climb test.
Time frame: Baseline to week 168
Population: ITT-intent-to-treat population, defined as all patients enrolled in the study who received patient IDs regardless of whether they received study drug or not
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PBO-QOW | Change From Baseline in 3-minute Stair Climb Test - ITT | Change from Baseline to Week 120 | 6.0 stairs/min | Standard Deviation 17.05 |
| PBO-QOW | Change From Baseline in 3-minute Stair Climb Test - ITT | Baseline | 33.1 stairs/min | Standard Deviation 15.6 |
| PBO-QOW | Change From Baseline in 3-minute Stair Climb Test - ITT | Change from baseline to week 168 | 8.9 stairs/min | Standard Deviation 17.57 |
| PBO-QOW | Change From Baseline in 3-minute Stair Climb Test - ITT | Change from Baseline to Week 24 | 4.7 stairs/min | Standard Deviation 9.65 |
| PBO-QOW | Change From Baseline in 3-minute Stair Climb Test - ITT | Change from Baseline to Week 72 | 8.9 stairs/min | Standard Deviation 15.44 |
| PBO-QW | Change From Baseline in 3-minute Stair Climb Test - ITT | Change from Baseline to Week 120 | 1.7 stairs/min | Standard Deviation 14.8 |
| PBO-QW | Change From Baseline in 3-minute Stair Climb Test - ITT | Change from Baseline to Week 72 | 1.2 stairs/min | Standard Deviation 14.95 |
| PBO-QW | Change From Baseline in 3-minute Stair Climb Test - ITT | Change from Baseline to Week 24 | 2.9 stairs/min | Standard Deviation 7.3 |
| PBO-QW | Change From Baseline in 3-minute Stair Climb Test - ITT | Change from baseline to week 168 | 5.5 stairs/min | Standard Deviation 15.44 |
| PBO-QW | Change From Baseline in 3-minute Stair Climb Test - ITT | Baseline | 26.9 stairs/min | Standard Deviation 12.08 |
| QOW-QOW | Change From Baseline in 3-minute Stair Climb Test - ITT | Change from Baseline to Week 72 | 5.5 stairs/min | Standard Deviation 11.96 |
| QOW-QOW | Change From Baseline in 3-minute Stair Climb Test - ITT | Baseline | 27.1 stairs/min | Standard Deviation 15.8 |
| QOW-QOW | Change From Baseline in 3-minute Stair Climb Test - ITT | Change from Baseline to Week 24 | 2.9 stairs/min | Standard Deviation 10.94 |
| QOW-QOW | Change From Baseline in 3-minute Stair Climb Test - ITT | Change from Baseline to Week 120 | 4.7 stairs/min | Standard Deviation 14.6 |
| QOW-QOW | Change From Baseline in 3-minute Stair Climb Test - ITT | Change from baseline to week 168 | 4.6 stairs/min | Standard Deviation 13.64 |
| QW-QW | Change From Baseline in 3-minute Stair Climb Test - ITT | Change from baseline to week 168 | 0.4 stairs/min | Standard Deviation 20.96 |
| QW-QW | Change From Baseline in 3-minute Stair Climb Test - ITT | Baseline | 29.6 stairs/min | Standard Deviation 16.44 |
| QW-QW | Change From Baseline in 3-minute Stair Climb Test - ITT | Change from Baseline to Week 120 | 5.8 stairs/min | Standard Deviation 13.42 |
| QW-QW | Change From Baseline in 3-minute Stair Climb Test - ITT | Change from Baseline to Week 72 | 5.3 stairs/min | Standard Deviation 9.88 |
| QW-QW | Change From Baseline in 3-minute Stair Climb Test - ITT | Change from Baseline to Week 24 | 4.8 stairs/min | Standard Deviation 8.06 |
| Total | Change From Baseline in 3-minute Stair Climb Test - ITT | Change from Baseline to Week 72 | 5.3 stairs/min | Standard Deviation 12.6 |
| Total | Change From Baseline in 3-minute Stair Climb Test - ITT | Change from Baseline to Week 120 | 4.8 stairs/min | Standard Deviation 14.65 |
| Total | Change From Baseline in 3-minute Stair Climb Test - ITT | Baseline | 28.9 stairs/min | Standard Deviation 15.42 |
| Total | Change From Baseline in 3-minute Stair Climb Test - ITT | Change from baseline to week 168 | 4.0 stairs/min | Standard Deviation 16.9 |
| Total | Change From Baseline in 3-minute Stair Climb Test - ITT | Change from Baseline to Week 24 | 3.8 stairs/min | Standard Deviation 9.25 |
Secondary
Change From Baseline in 3-minute Stair Climb Test - MPP
Efficacy was assessed by changes from baseline in 3-minute stair climb test.
Time frame: Baseline to week 168
Population: MPP- modified per-protocol population, define as the ITT(intent to treat) after removing patients who had orthosurgery in first 120 weeks or \<96 doses in first 120 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PBO-QOW | Change From Baseline in 3-minute Stair Climb Test - MPP | Change from Baseline to Week 120 | 9.1 stairs/min | Standard Deviation 13.38 |
| PBO-QOW | Change From Baseline in 3-minute Stair Climb Test - MPP | Baseline | 33.1 stairs/min | Standard Deviation 14.12 |
| PBO-QOW | Change From Baseline in 3-minute Stair Climb Test - MPP | Change from baseline to week 168 | 12.4 stairs/min | Standard Deviation 23.03 |
| PBO-QOW | Change From Baseline in 3-minute Stair Climb Test - MPP | Change from Baseline to Week 24 | 3.4 stairs/min | Standard Deviation 8.09 |
| PBO-QOW | Change From Baseline in 3-minute Stair Climb Test - MPP | Change from Baseline to Week 72 | 10.4 stairs/min | Standard Deviation 13.77 |
| PBO-QW | Change From Baseline in 3-minute Stair Climb Test - MPP | Change from Baseline to Week 120 | 4.2 stairs/min | Standard Deviation 12.49 |
| PBO-QW | Change From Baseline in 3-minute Stair Climb Test - MPP | Change from Baseline to Week 72 | 6.1 stairs/min | Standard Deviation 10.56 |
| PBO-QW | Change From Baseline in 3-minute Stair Climb Test - MPP | Change from Baseline to Week 24 | 3.6 stairs/min | Standard Deviation 8.63 |
| PBO-QW | Change From Baseline in 3-minute Stair Climb Test - MPP | Change from baseline to week 168 | 4.3 stairs/min | Standard Deviation 17.82 |
| PBO-QW | Change From Baseline in 3-minute Stair Climb Test - MPP | Baseline | 24.8 stairs/min | Standard Deviation 13.92 |
| QOW-QOW | Change From Baseline in 3-minute Stair Climb Test - MPP | Change from Baseline to Week 72 | 7.4 stairs/min | Standard Deviation 12.53 |
| QOW-QOW | Change From Baseline in 3-minute Stair Climb Test - MPP | Baseline | 25.6 stairs/min | Standard Deviation 13.73 |
| QOW-QOW | Change From Baseline in 3-minute Stair Climb Test - MPP | Change from Baseline to Week 24 | 5.0 stairs/min | Standard Deviation 11.46 |
| QOW-QOW | Change From Baseline in 3-minute Stair Climb Test - MPP | Change from Baseline to Week 120 | 8.1 stairs/min | Standard Deviation 13.83 |
| QOW-QOW | Change From Baseline in 3-minute Stair Climb Test - MPP | Change from baseline to week 168 | 6.0 stairs/min | Standard Deviation 14.59 |
| QW-QW | Change From Baseline in 3-minute Stair Climb Test - MPP | Change from baseline to week 168 | -2.6 stairs/min | Standard Deviation 18.47 |
| QW-QW | Change From Baseline in 3-minute Stair Climb Test - MPP | Baseline | 31.3 stairs/min | Standard Deviation 16.22 |
| QW-QW | Change From Baseline in 3-minute Stair Climb Test - MPP | Change from Baseline to Week 120 | 7.2 stairs/min | Standard Deviation 12.58 |
| QW-QW | Change From Baseline in 3-minute Stair Climb Test - MPP | Change from Baseline to Week 72 | 5.7 stairs/min | Standard Deviation 9.98 |
| QW-QW | Change From Baseline in 3-minute Stair Climb Test - MPP | Change from Baseline to Week 24 | 3.9 stairs/min | Standard Deviation 7.67 |
| Total | Change From Baseline in 3-minute Stair Climb Test - MPP | Change from Baseline to Week 72 | 7.1 stairs/min | Standard Deviation 11.61 |
| Total | Change From Baseline in 3-minute Stair Climb Test - MPP | Change from Baseline to Week 120 | 7.4 stairs/min | Standard Deviation 13.05 |
| Total | Change From Baseline in 3-minute Stair Climb Test - MPP | Baseline | 28.7 stairs/min | Standard Deviation 14.93 |
| Total | Change From Baseline in 3-minute Stair Climb Test - MPP | Change from baseline to week 168 | 3.3 stairs/min | Standard Deviation 17.39 |
| Total | Change From Baseline in 3-minute Stair Climb Test - MPP | Change from Baseline to Week 24 | 4.1 stairs/min | Standard Deviation 9.23 |
Secondary
Change From Baseline in Urine Keratan Sulfate - ITT
Efficacy was assessed by changes from baseline in urine keratan sulfate (normalized to urine creatinine.)
Time frame: Baseline to week 168
Population: ITT-intent-to-treat population, defined as all patients enrolled in the study who received patient IDs regardless of whether they received study drug or not
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PBO-QOW | Change From Baseline in Urine Keratan Sulfate - ITT | Percent Change from Baseline to Week 120 | -55.5 ug/mg | Standard Deviation 18.6 |
| PBO-QOW | Change From Baseline in Urine Keratan Sulfate - ITT | Baseline | 22.7 ug/mg | Standard Deviation 15.27 |
| PBO-QOW | Change From Baseline in Urine Keratan Sulfate - ITT | Percent Change from Baseline to Week 168 | -31.9 ug/mg | Standard Deviation 31.2 |
| PBO-QOW | Change From Baseline in Urine Keratan Sulfate - ITT | Percent Change from Baseline to Week 24 | 3.4 ug/mg | Standard Deviation 29.15 |
| PBO-QOW | Change From Baseline in Urine Keratan Sulfate - ITT | Percent Change from Baseline to Week 72 | -54.1 ug/mg | Standard Deviation 17.21 |
| PBO-QW | Change From Baseline in Urine Keratan Sulfate - ITT | Percent Change from Baseline to Week 120 | -62.2 ug/mg | Standard Deviation 15.39 |
| PBO-QW | Change From Baseline in Urine Keratan Sulfate - ITT | Percent Change from Baseline to Week 72 | -56.8 ug/mg | Standard Deviation 13.69 |
| PBO-QW | Change From Baseline in Urine Keratan Sulfate - ITT | Percent Change from Baseline to Week 24 | -11.3 ug/mg | Standard Deviation 23.68 |
| PBO-QW | Change From Baseline in Urine Keratan Sulfate - ITT | Percent Change from Baseline to Week 168 | -38.3 ug/mg | Standard Deviation 47.43 |
| PBO-QW | Change From Baseline in Urine Keratan Sulfate - ITT | Baseline | 28.5 ug/mg | Standard Deviation 14.89 |
| QOW-QOW | Change From Baseline in Urine Keratan Sulfate - ITT | Percent Change from Baseline to Week 72 | -55.6 ug/mg | Standard Deviation 14.23 |
| QOW-QOW | Change From Baseline in Urine Keratan Sulfate - ITT | Baseline | 28.6 ug/mg | Standard Deviation 21.17 |
| QOW-QOW | Change From Baseline in Urine Keratan Sulfate - ITT | Percent Change from Baseline to Week 24 | -35.2 ug/mg | Standard Deviation 20.7 |
| QOW-QOW | Change From Baseline in Urine Keratan Sulfate - ITT | Percent Change from Baseline to Week 120 | -55.8 ug/mg | Standard Deviation 26.56 |
| QOW-QOW | Change From Baseline in Urine Keratan Sulfate - ITT | Percent Change from Baseline to Week 168 | -28.5 ug/mg | Standard Deviation 35.14 |
| QW-QW | Change From Baseline in Urine Keratan Sulfate - ITT | Percent Change from Baseline to Week 168 | -39.3 ug/mg | Standard Deviation 47.39 |
| QW-QW | Change From Baseline in Urine Keratan Sulfate - ITT | Baseline | 26.9 ug/mg | Standard Deviation 14.11 |
| QW-QW | Change From Baseline in Urine Keratan Sulfate - ITT | Percent Change from Baseline to Week 120 | -61.5 ug/mg | Standard Deviation 20.59 |
| QW-QW | Change From Baseline in Urine Keratan Sulfate - ITT | Percent Change from Baseline to Week 72 | -53.7 ug/mg | Standard Deviation 17.45 |
| QW-QW | Change From Baseline in Urine Keratan Sulfate - ITT | Percent Change from Baseline to Week 24 | -45.1 ug/mg | Standard Deviation 19.89 |
| Total | Change From Baseline in Urine Keratan Sulfate - ITT | Percent Change from Baseline to Week 72 | -55.0 ug/mg | Standard Deviation 15.61 |
| Total | Change From Baseline in Urine Keratan Sulfate - ITT | Percent Change from Baseline to Week 120 | -58.7 ug/mg | Standard Deviation 21.88 |
| Total | Change From Baseline in Urine Keratan Sulfate - ITT | Baseline | 27.1 ug/mg | Standard Deviation 17.05 |
| Total | Change From Baseline in Urine Keratan Sulfate - ITT | Percent Change from Baseline to Week 168 | -33.7 ug/mg | Standard Deviation 40.06 |
| Total | Change From Baseline in Urine Keratan Sulfate - ITT | Percent Change from Baseline to Week 24 | -28.2 ug/mg | Standard Deviation 28.46 |
Secondary
Change From Baseline in Urine Keratan Sulfate - MPP
Efficacy was assessed by changes from baseline in urine keratan sulfate (normalized to urine creatinine.)
Time frame: Baseline to week 168
Population: MPP- modified per-protocol population, define as the ITT(intent to treat) after removing patients who had orthosurgery in first 120 weeks or \<96 doses in first 120 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PBO-QOW | Change From Baseline in Urine Keratan Sulfate - MPP | Percent Change from Baseline to Week 120 | -58.3 ug/mg | Standard Deviation 15.87 |
| PBO-QOW | Change From Baseline in Urine Keratan Sulfate - MPP | Baseline | 21.2 ug/mg | Standard Deviation 15.55 |
| PBO-QOW | Change From Baseline in Urine Keratan Sulfate - MPP | Percent Change from Baseline to Week 168 | -9.9 ug/mg | Standard Deviation 23.48 |
| PBO-QOW | Change From Baseline in Urine Keratan Sulfate - MPP | Percent Change from Baseline to Week 24 | 1.2 ug/mg | Standard Deviation 24.34 |
| PBO-QOW | Change From Baseline in Urine Keratan Sulfate - MPP | Percent Change from Baseline to Week 72 | -51.7 ug/mg | Standard Deviation 19.34 |
| PBO-QW | Change From Baseline in Urine Keratan Sulfate - MPP | Percent Change from Baseline to Week 120 | -64.2 ug/mg | Standard Deviation 16.58 |
| PBO-QW | Change From Baseline in Urine Keratan Sulfate - MPP | Percent Change from Baseline to Week 72 | -58.8 ug/mg | Standard Deviation 14.6 |
| PBO-QW | Change From Baseline in Urine Keratan Sulfate - MPP | Percent Change from Baseline to Week 24 | -12.9 ug/mg | Standard Deviation 24.29 |
| PBO-QW | Change From Baseline in Urine Keratan Sulfate - MPP | Percent Change from Baseline to Week 168 | -41.6 ug/mg | Standard Deviation 46.05 |
| PBO-QW | Change From Baseline in Urine Keratan Sulfate - MPP | Baseline | 27.5 ug/mg | Standard Deviation 15.24 |
| QOW-QOW | Change From Baseline in Urine Keratan Sulfate - MPP | Percent Change from Baseline to Week 72 | -56.9 ug/mg | Standard Deviation 13.55 |
| QOW-QOW | Change From Baseline in Urine Keratan Sulfate - MPP | Baseline | 27.2 ug/mg | Standard Deviation 22.9 |
| QOW-QOW | Change From Baseline in Urine Keratan Sulfate - MPP | Percent Change from Baseline to Week 24 | -35.5 ug/mg | Standard Deviation 22.62 |
| QOW-QOW | Change From Baseline in Urine Keratan Sulfate - MPP | Percent Change from Baseline to Week 120 | -62.1 ug/mg | Standard Deviation 15.97 |
| QOW-QOW | Change From Baseline in Urine Keratan Sulfate - MPP | Percent Change from Baseline to Week 168 | -27.1 ug/mg | Standard Deviation 37.28 |
| QW-QW | Change From Baseline in Urine Keratan Sulfate - MPP | Percent Change from Baseline to Week 168 | -43.0 ug/mg | Standard Deviation 34.07 |
| QW-QW | Change From Baseline in Urine Keratan Sulfate - MPP | Baseline | 24.9 ug/mg | Standard Deviation 13.13 |
| QW-QW | Change From Baseline in Urine Keratan Sulfate - MPP | Percent Change from Baseline to Week 120 | -61.8 ug/mg | Standard Deviation 21.28 |
| QW-QW | Change From Baseline in Urine Keratan Sulfate - MPP | Percent Change from Baseline to Week 72 | -53.7 ug/mg | Standard Deviation 17.87 |
| QW-QW | Change From Baseline in Urine Keratan Sulfate - MPP | Percent Change from Baseline to Week 24 | -44.9 ug/mg | Standard Deviation 19.6 |
| Total | Change From Baseline in Urine Keratan Sulfate - MPP | Percent Change from Baseline to Week 72 | -55.3 ug/mg | Standard Deviation 16.21 |
| Total | Change From Baseline in Urine Keratan Sulfate - MPP | Percent Change from Baseline to Week 120 | -61.7 ug/mg | Standard Deviation 17.98 |
| Total | Change From Baseline in Urine Keratan Sulfate - MPP | Baseline | 25.5 ug/mg | Standard Deviation 17.61 |
| Total | Change From Baseline in Urine Keratan Sulfate - MPP | Percent Change from Baseline to Week 168 | -32.8 ug/mg | Standard Deviation 37.11 |
| Total | Change From Baseline in Urine Keratan Sulfate - MPP | Percent Change from Baseline to Week 24 | -29.7 ug/mg | Standard Deviation 27.52 |