Hypophosphatasia
Conditions
Keywords
Hypophosphatasia, HPP, Bone Disease, Soft Bones, Low Alkaline Phosphatase, genetic metabolic disorder, alkaline phosphatase, tissue-specific alkaline phosphatase (TNSALP), rickets, osteomalacia
Brief summary
This clinical trial was conducted to study hypophosphatasia (HPP), a bone disorder caused by gene mutations or changes. These gene mutations cause low levels of an enzyme needed to harden bone. The purpose of this study was to test the safety and efficacy of two doses of the study drug called asfotase alfa as compared to a control group to see effects on adolescents and adults with HPP.
Detailed description
Asfotase alfa was formerly referred to as ENB-0040 Hypophosphatasia (HPP) is a life-threatening, genetic, and ultra-rare metabolic disease characterized by defective bone mineralization and impaired phosphate and calcium regulation that can lead to progressive damage to multiple vital organs, including destruction and deformity of bones, profound muscle weakness, seizures, impaired renal function, and respiratory failure. There are limited data available on the natural course of this disease over time, particularly in patients with the juvenile-onset form.
Interventions
DRUGasfotase alfa
Cohort 1: Daily SC injections of 0.3 mg/kg asfotase alfa (total of 2.1 mg/kg/week)
Sponsors
Alexion Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
13 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
Patients must meet all of the following inclusion criteria to be eligible for participation in this study: * Patients or their legal representative(s) must provide written informed consent prior to undergoing any study-related procedures * Patients must be ≥ 13 and ≤ 65 years of age at the time of study enrollment * Female patients of childbearing potential and sexually mature males must agree to use a medically acceptable form of birth control; for the purposes of this study, females are considered of non-childbearing potential if they are surgically sterile (i.e., have undergone a total hysterectomy, bilateral salpingo-oophorectomy or tubal ligation) or are post-menopausal, defined as having complete cessation of menstruation for at least 1 year after 45 years of age * Patients must have a pre-established clinical diagnosis of HPP as indicated by: * Serum alkaline phosphatase (ALP) below the age-adjusted normal range * Plasma PLP at least twice the upper limit of normal (no vitamin B6 administered for at least 1 week prior to determination) * Evidence of osteopenia or osteomalacia on skeletal radiographs * Patients must have osteomalacia on bone biopsy, characterized by an MLT z-score of +2 or more (results from ENB-001-08 may be used) * Patients must be willing to comply with study procedures and the visit schedule
Exclusion criteria
Patients will be excluded from participation in this study if they meet any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 24 for Plasma Pyridoxal-5' Phosphate (PLP) | Baseline, Week 24 | Blood samples were collected to evaluate the effect of asfotase alfa on reduction in plasma pyridoxal-5' phosphate (PLP) |
| Change From Baseline to Week 24 for Plasma Inorganic Pyrophosphate (PPi) | Baseline, Week 24 | Blood samples were collected to evaluate the effect of asfotase alfa on reduction in plasma inorganic pyrophosphate (PPi) |
| Safety and Tolerability of Asfotase Alfa | Up to 288 weeks exposure to asfotase alfa | The safety and tolerability of daily subcutaneous (SC) injections of asfotase alfa was assessed by routine monitoring of patients for treatment-emergent adverse events (TEAEs) and injection-associated reactions (IARs). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in HPP-related Osteomalacia as Measured by Trans-iliac Crest Bone Biopsy: Osteoid Volume/Bone Volume | Baseline, Week 24 (Control group), and Week 48 (Asfotase alfa groups). | A trans-iliac crest bone biopsy was performed to quantify changes from Baseline in histomorphometric parameters relevant for evaluation of osteomalacia severity, including Osteoid Volume/Bone Volume (%). The difference in time under observation between asfotase alfa groups (Week 48) and control group (Week 24) resulted from study design, ie, control subjects transitioned to active treatment after the Week 24 visit. |
| Change From Baseline in Bone Mineral Content (BMC) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Baseline, every 24 weeks through Week 96, then every 48 weeks until Week 288. | A DXA scan was performed to evaluate bone mineral content (BMC) of the spine, hip, and whole body during the primary (first 24 weeks) and extension treatment periods (up to 288 weeks). |
| Change From Baseline in HPP-related Osteomalacia as Measured by Trans-iliac Crest Bone Biopsy: Mineralization Lag Time | Baseline, Week 24 (Control group), and Week 48 (Asfotase alfa groups). | A trans-iliac crest bone biopsy was performed to quantify changes from Baseline in histomorphometric parameters relevant for evaluation of osteomalacia severity, including Mineralization Lag Time (days). The difference in time under observation between asfotase alfa groups (Week 48) and control group (Week 24) resulted from study design, ie, control subjects transitioned to active treatment after the Week 24 visit. |
| Change From Baseline in HPP-related Osteomalacia as Measured by Trans-iliac Crest Bone Biopsy: Osteoid Thickness | Baseline, Week 24 (Control group), and Week 48 (Asfotase alfa groups). | A trans-iliac crest bone biopsy was performed to quantify changes from Baseline in histomorphometric parameters relevant for evaluation of osteomalacia severity, including Osteoid Thickness (um). The difference in time under observation between asfotase alfa groups (Week 48) and control group (Week 24) resulted from study design, ie, control subjects transitioned to active treatment after the Week 24 visit. |
| Change From Baseline in Bone Mineral Density (BMD) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Baseline, every 24 weeks through Week 96, then every 48 weeks until Week 288. | A DXA scan was performed to evaluate bone bone mineral density (BMD) of the spine, hip, and whole body during the primary (first 24 weeks) and extension treatment periods (up to 288 weeks). |
| Change in Walking Ability as Measured by the Six-Minute Walk Test (6MWT) | Baseline, Week 24 (primary treatment period) and up to 288 weeks of asfotase alfa exposure | The patient was instructed to walk the length of a pre-measured hallway for 6 minutes. The primary measurement was distance walked (in meters). |
Countries
Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 0.3 mg/kg Asfotase Alfa Asfotase alfa: Cohort 1: Daily SC injections of 0.3 mg/kg asfotase alfa (total of 2.1 mg/kg/week) during Primary Treatment Period through Week 24.
Following completion of the Week 24 visit, all subjects were eligible to participate in an open-label extension treatment period. In this extension period, all subjects were treated with daily SC injections of 0.5 mg/kg/day asfotase alfa (a total of 3.5 mg/kg/week) for approximately 24 weeks, then subjects received 1 mg/kg/day 6 days/week until regulatory approval of the drug. | 7 |
| 0.5 mg/kg Asfotase Alfa Asfotase alfa: Cohort 2: Daily SC injections of 0.5 mg/kg asfotase alfa (3.5 mg/kg/week total) during Primary Treatment Period through Week 24.
Following completion of the Week 24 visit, all subjects were eligible to participate in an open-label extension treatment period. In this extension period, all subjects were treated with daily SC injections of 0.5 mg/kg/day asfotase alfa (a total of 3.5 mg/kg/week) for approximately 24 weeks, then subjects received 1 mg/kg/day 6 days/week until regulatory approval of the drug. | 6 |
| Concurrent Control No asfotase alfa during first 24 weeks (primary treatment period).
Following completion of the Week 24 visit, all subjects randomized to the concurrent control cohort were eligible to participate in an open-label extension treatment period. In this extension period, all subjects were treated with daily SC injections of 0.5 mg/kg/day asfotase alfa (a total of 3.5 mg/kg/week) for approximately 24 weeks, then subjects received 1 mg/kg/day 6 days/week until regulatory approval of the drug | 6 |
| Total | 19 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Extension Treatment Period | Adverse Event | 0 | 1 | 0 |
| Extension Treatment Period | Noncompliance | 0 | 0 | 1 |
| Extension Treatment Period | Withdrawal by Subject | 2 | 0 | 1 |
Baseline characteristics
| Characteristic | 0.3 mg/kg Asfotase Alfa | Total | Concurrent Control | 0.5 mg/kg Asfotase Alfa |
|---|---|---|---|---|
| Age, Continuous | 45.0 years | 53.0 years | 21.0 years | 55.0 years |
| Age, Customized Age at Onset of Symptoms | 2.0 years | 2.0 years | 0.88 years | 2.0 years |
| Age, Customized Age Group Adolescent (12-17 years) | 2 Participants | 6 Participants | 3 Participants | 1 Participants |
| Age, Customized Age Group Adult (≥ 18 years) | 5 Participants | 13 Participants | 3 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants | 19 Participants | 6 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Hypophosphatasia (HPP) Phenotype Adult (≥ 18 years) | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Hypophosphatasia (HPP) Phenotype Infantile (<6 months) | 1 Participants | 4 Participants | 1 Participants | 2 Participants |
| Hypophosphatasia (HPP) Phenotype Juvenile (≥ 6 months to < 18 years) | 5 Participants | 14 Participants | 5 Participants | 4 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) White | 7 Participants | 18 Participants | 5 Participants | 6 Participants |
| Sex: Female, Male Female | 6 Participants | 12 Participants | 2 Participants | 4 Participants |
| Sex: Female, Male Male | 1 Participants | 7 Participants | 4 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 7 | 0 / 6 | 0 / 6 | 0 / 19 |
| other Total, other adverse events | 7 / 7 | 6 / 6 | 6 / 6 | 19 / 19 |
| serious Total, serious adverse events | 1 / 7 | 1 / 6 | 2 / 6 | 9 / 19 |
Outcome results
Primary
Change From Baseline to Week 24 for Plasma Inorganic Pyrophosphate (PPi)
Blood samples were collected to evaluate the effect of asfotase alfa on reduction in plasma inorganic pyrophosphate (PPi)
Time frame: Baseline, Week 24
Population: Full analysis set (intent-to-treat, all randomized patients)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 0.3 mg/kg Asfotase Alfa | Change From Baseline to Week 24 for Plasma Inorganic Pyrophosphate (PPi) | -2.027 uM | Standard Deviation 1.4381 |
| 0.5 mg/kg Asfotase Alfa | Change From Baseline to Week 24 for Plasma Inorganic Pyrophosphate (PPi) | -2.185 uM | Standard Deviation 1.3304 |
| Concurrent Control | Change From Baseline to Week 24 for Plasma Inorganic Pyrophosphate (PPi) | -1.052 uM | Standard Deviation 2.9248 |
| Combined Asfotase Alfa Group | Change From Baseline to Week 24 for Plasma Inorganic Pyrophosphate (PPi) | -2.100 uM | Standard Deviation 1.3335 |
Comparison: PPi Change from Baseline to Week 24p-value: 0.071595% CI: [-3.21, 0.23]Wilcoxon rank-sum
Primary
Change From Baseline to Week 24 for Plasma Pyridoxal-5' Phosphate (PLP)
Blood samples were collected to evaluate the effect of asfotase alfa on reduction in plasma pyridoxal-5' phosphate (PLP)
Time frame: Baseline, Week 24
Population: Full analysis set (intent-to-treat, all randomized patients)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 0.3 mg/kg Asfotase Alfa | Change From Baseline to Week 24 for Plasma Pyridoxal-5' Phosphate (PLP) | -254.96 ng/mL | Standard Deviation 196.206 |
| 0.5 mg/kg Asfotase Alfa | Change From Baseline to Week 24 for Plasma Pyridoxal-5' Phosphate (PLP) | -564.27 ng/mL | Standard Deviation 624.009 |
| Concurrent Control | Change From Baseline to Week 24 for Plasma Pyridoxal-5' Phosphate (PLP) | 3.13 ng/mL | Standard Deviation 242.721 |
| Combined Asfotase Alfa Group | Change From Baseline to Week 24 for Plasma Pyridoxal-5' Phosphate (PLP) | -397.72 ng/mL | Standard Deviation 455.249 |
Comparison: PLP Change from Baseline to Week 24p-value: 0.028595% CI: [-626.4, -59.2]Wilcoxon rank-sum
Primary
Safety and Tolerability of Asfotase Alfa
The safety and tolerability of daily subcutaneous (SC) injections of asfotase alfa was assessed by routine monitoring of patients for treatment-emergent adverse events (TEAEs) and injection-associated reactions (IARs).
Time frame: Up to 288 weeks exposure to asfotase alfa
Population: Safety Set. Control group and asfotase alfa Cohorts during the primary treatment period (first 24 weeks of study); all patients with asfotase alfa exposure during open-label extension treatment period.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 0.3 mg/kg Asfotase Alfa | Safety and Tolerability of Asfotase Alfa | Any TEAE | 243 Number of Treatment-Emergent Events |
| 0.3 mg/kg Asfotase Alfa | Safety and Tolerability of Asfotase Alfa | TEAEs leading to withdrawal | 0 Number of Treatment-Emergent Events |
| 0.3 mg/kg Asfotase Alfa | Safety and Tolerability of Asfotase Alfa | Serious TEAEs | 1 Number of Treatment-Emergent Events |
| 0.3 mg/kg Asfotase Alfa | Safety and Tolerability of Asfotase Alfa | Not related TEAEs | 110 Number of Treatment-Emergent Events |
| 0.3 mg/kg Asfotase Alfa | Safety and Tolerability of Asfotase Alfa | Deaths | 0 Number of Treatment-Emergent Events |
| 0.3 mg/kg Asfotase Alfa | Safety and Tolerability of Asfotase Alfa | Related TEAEs | 133 Number of Treatment-Emergent Events |
| 0.3 mg/kg Asfotase Alfa | Safety and Tolerability of Asfotase Alfa | Injection site reactions | 133 Number of Treatment-Emergent Events |
| 0.5 mg/kg Asfotase Alfa | Safety and Tolerability of Asfotase Alfa | TEAEs leading to withdrawal | 0 Number of Treatment-Emergent Events |
| 0.5 mg/kg Asfotase Alfa | Safety and Tolerability of Asfotase Alfa | Injection site reactions | 12 Number of Treatment-Emergent Events |
| 0.5 mg/kg Asfotase Alfa | Safety and Tolerability of Asfotase Alfa | Related TEAEs | 12 Number of Treatment-Emergent Events |
| 0.5 mg/kg Asfotase Alfa | Safety and Tolerability of Asfotase Alfa | Serious TEAEs | 1 Number of Treatment-Emergent Events |
| 0.5 mg/kg Asfotase Alfa | Safety and Tolerability of Asfotase Alfa | Deaths | 0 Number of Treatment-Emergent Events |
| 0.5 mg/kg Asfotase Alfa | Safety and Tolerability of Asfotase Alfa | Not related TEAEs | 69 Number of Treatment-Emergent Events |
| 0.5 mg/kg Asfotase Alfa | Safety and Tolerability of Asfotase Alfa | Any TEAE | 81 Number of Treatment-Emergent Events |
| Concurrent Control | Safety and Tolerability of Asfotase Alfa | Injection site reactions | 0 Number of Treatment-Emergent Events |
| Concurrent Control | Safety and Tolerability of Asfotase Alfa | Any TEAE | 45 Number of Treatment-Emergent Events |
| Concurrent Control | Safety and Tolerability of Asfotase Alfa | Not related TEAEs | 45 Number of Treatment-Emergent Events |
| Concurrent Control | Safety and Tolerability of Asfotase Alfa | Related TEAEs | 0 Number of Treatment-Emergent Events |
| Concurrent Control | Safety and Tolerability of Asfotase Alfa | Serious TEAEs | 4 Number of Treatment-Emergent Events |
| Concurrent Control | Safety and Tolerability of Asfotase Alfa | TEAEs leading to withdrawal | 0 Number of Treatment-Emergent Events |
| Concurrent Control | Safety and Tolerability of Asfotase Alfa | Deaths | 0 Number of Treatment-Emergent Events |
| Combined Asfotase Alfa Group | Safety and Tolerability of Asfotase Alfa | Related TEAEs | 414 Number of Treatment-Emergent Events |
| Combined Asfotase Alfa Group | Safety and Tolerability of Asfotase Alfa | Deaths | 0 Number of Treatment-Emergent Events |
| Combined Asfotase Alfa Group | Safety and Tolerability of Asfotase Alfa | TEAEs leading to withdrawal | 2 Number of Treatment-Emergent Events |
| Combined Asfotase Alfa Group | Safety and Tolerability of Asfotase Alfa | Not related TEAEs | 731 Number of Treatment-Emergent Events |
| Combined Asfotase Alfa Group | Safety and Tolerability of Asfotase Alfa | Any TEAE | 1145 Number of Treatment-Emergent Events |
| Combined Asfotase Alfa Group | Safety and Tolerability of Asfotase Alfa | Serious TEAEs | 29 Number of Treatment-Emergent Events |
| Combined Asfotase Alfa Group | Safety and Tolerability of Asfotase Alfa | Injection site reactions | 385 Number of Treatment-Emergent Events |
Secondary
Change From Baseline in Bone Mineral Content (BMC) as Measured by Dual-energy X-ray Absorptiometry (DXA)
A DXA scan was performed to evaluate bone mineral content (BMC) of the spine, hip, and whole body during the primary (first 24 weeks) and extension treatment periods (up to 288 weeks).
Time frame: Baseline, every 24 weeks through Week 96, then every 48 weeks until Week 288.
Population: Full analysis set (intent-to-treat, all randomized patients)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 0.3 mg/kg Asfotase Alfa | Change From Baseline in Bone Mineral Content (BMC) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Lumbar Spine BMC Last Overall Exposure | 4.306 g | Standard Deviation 14.5714 |
| 0.3 mg/kg Asfotase Alfa | Change From Baseline in Bone Mineral Content (BMC) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Lumbar Spine BMC Week 240 | 3.536 g | Standard Deviation 17.0957 |
| 0.3 mg/kg Asfotase Alfa | Change From Baseline in Bone Mineral Content (BMC) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Hip total BMC Week 144 | 1.630 g | Standard Deviation 1.8719 |
| 0.3 mg/kg Asfotase Alfa | Change From Baseline in Bone Mineral Content (BMC) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Whole Body BMC Week 48 | 49.820 g | — |
| 0.3 mg/kg Asfotase Alfa | Change From Baseline in Bone Mineral Content (BMC) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Lumbar Spine BMC Week 288 | 20.190 g | — |
| 0.3 mg/kg Asfotase Alfa | Change From Baseline in Bone Mineral Content (BMC) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Whole Body BMC Week 24 | -21.871 g | Standard Deviation 35.437 |
| 0.3 mg/kg Asfotase Alfa | Change From Baseline in Bone Mineral Content (BMC) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Hip total BMC Week 48 | 1.160 g | — |
| 0.3 mg/kg Asfotase Alfa | Change From Baseline in Bone Mineral Content (BMC) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Whole Body BMC Week 288 | -243.080 g | — |
| 0.3 mg/kg Asfotase Alfa | Change From Baseline in Bone Mineral Content (BMC) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Hip total BMC Week 192 | 1.080 g | Standard Deviation 2.0082 |
| 0.3 mg/kg Asfotase Alfa | Change From Baseline in Bone Mineral Content (BMC) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Hip total BMC Week 240 | 0.550 g | Standard Deviation 2.4042 |
| 0.3 mg/kg Asfotase Alfa | Change From Baseline in Bone Mineral Content (BMC) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Hip total BMC Week 24 | -3.288 g | Standard Deviation 7.7669 |
| 0.3 mg/kg Asfotase Alfa | Change From Baseline in Bone Mineral Content (BMC) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Whole Body BMC Week 240 | -97.706 g | Standard Deviation 106.6581 |
| 0.3 mg/kg Asfotase Alfa | Change From Baseline in Bone Mineral Content (BMC) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Hip Total BMC Last Overall Exposure | 0.080 g | Standard Deviation 1.8713 |
| 0.3 mg/kg Asfotase Alfa | Change From Baseline in Bone Mineral Content (BMC) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Whole Body BMC Week 192 | -121.916 g | Standard Deviation 92.0001 |
| 0.3 mg/kg Asfotase Alfa | Change From Baseline in Bone Mineral Content (BMC) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Lumbar Spine BMC Week 24 | 2.477 g | Standard Deviation 2.5616 |
| 0.3 mg/kg Asfotase Alfa | Change From Baseline in Bone Mineral Content (BMC) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Whole Body BMC Last Overall Exposure | -113.296 g | Standard Deviation 178.805 |
| 0.3 mg/kg Asfotase Alfa | Change From Baseline in Bone Mineral Content (BMC) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Lumbar Spine BMC Week 48 | 2.420 g | — |
| 0.3 mg/kg Asfotase Alfa | Change From Baseline in Bone Mineral Content (BMC) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Hip total BMC Week 96 | 0.082 g | Standard Deviation 1.4046 |
| 0.3 mg/kg Asfotase Alfa | Change From Baseline in Bone Mineral Content (BMC) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Whole Body BMC Week 144 | -48.236 g | Standard Deviation 111.6604 |
| 0.3 mg/kg Asfotase Alfa | Change From Baseline in Bone Mineral Content (BMC) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Lumbar Spine BMC Week 96 | 3.356 g | Standard Deviation 4.4566 |
| 0.3 mg/kg Asfotase Alfa | Change From Baseline in Bone Mineral Content (BMC) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Lumbar Spine BMC Week 144 | 2.086 g | Standard Deviation 5.2198 |
| 0.3 mg/kg Asfotase Alfa | Change From Baseline in Bone Mineral Content (BMC) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Whole Body BMC Week 96 | 7.537 g | Standard Deviation 74.2838 |
| 0.3 mg/kg Asfotase Alfa | Change From Baseline in Bone Mineral Content (BMC) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Lumbar Spine BMC Week 192 | 2.094 g | Standard Deviation 16.4419 |
| 0.5 mg/kg Asfotase Alfa | Change From Baseline in Bone Mineral Content (BMC) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Lumbar Spine BMC Week 48 | 5.550 g | — |
| 0.5 mg/kg Asfotase Alfa | Change From Baseline in Bone Mineral Content (BMC) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Hip Total BMC Week 288 | -2.780 g | — |
| 0.5 mg/kg Asfotase Alfa | Change From Baseline in Bone Mineral Content (BMC) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Whole Body BMC Week 288 | -144.660 g | — |
| 0.5 mg/kg Asfotase Alfa | Change From Baseline in Bone Mineral Content (BMC) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Whole Body BMC Week 48 | 72.530 g | — |
| 0.5 mg/kg Asfotase Alfa | Change From Baseline in Bone Mineral Content (BMC) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Whole Body BMC Week 192 | 23.938 g | Standard Deviation 195.8402 |
| 0.5 mg/kg Asfotase Alfa | Change From Baseline in Bone Mineral Content (BMC) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Lumbar Spine BMC Week 240 | 3.298 g | Standard Deviation 2.4931 |
| 0.5 mg/kg Asfotase Alfa | Change From Baseline in Bone Mineral Content (BMC) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Whole Body BMC Week 96 | 59.604 g | Standard Deviation 97.9214 |
| 0.5 mg/kg Asfotase Alfa | Change From Baseline in Bone Mineral Content (BMC) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Hip Total BMC Last Overall Exposure | 3.604 g | Standard Deviation 5.8284 |
| 0.5 mg/kg Asfotase Alfa | Change From Baseline in Bone Mineral Content (BMC) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Hip total BMC Week 24 | 1.214 g | Standard Deviation 2.2154 |
| 0.5 mg/kg Asfotase Alfa | Change From Baseline in Bone Mineral Content (BMC) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Lumbar Spine BMC Week 288 | 6.500 g | — |
| 0.5 mg/kg Asfotase Alfa | Change From Baseline in Bone Mineral Content (BMC) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Whole Body BMC Week 24 | 41.454 g | Standard Deviation 20.0358 |
| 0.5 mg/kg Asfotase Alfa | Change From Baseline in Bone Mineral Content (BMC) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Lumbar Spine BMC Week 192 | 6.162 g | Standard Deviation 4.1628 |
| 0.5 mg/kg Asfotase Alfa | Change From Baseline in Bone Mineral Content (BMC) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Lumbar Spine BMC Last Overall Exposure | 5.130 g | Standard Deviation 3.593 |
| 0.5 mg/kg Asfotase Alfa | Change From Baseline in Bone Mineral Content (BMC) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Hip total BMC Week 144 | 5.043 g | Standard Deviation 5.5955 |
| 0.5 mg/kg Asfotase Alfa | Change From Baseline in Bone Mineral Content (BMC) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Whole Body BMC Last Overall Exposure | 11.252 g | Standard Deviation 217.5674 |
| 0.5 mg/kg Asfotase Alfa | Change From Baseline in Bone Mineral Content (BMC) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Lumbar Spine BMC Week 144 | 5.828 g | Standard Deviation 3.9791 |
| 0.5 mg/kg Asfotase Alfa | Change From Baseline in Bone Mineral Content (BMC) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Lumbar Spine BMC Week 24 | 2.768 g | Standard Deviation 2.0007 |
| 0.5 mg/kg Asfotase Alfa | Change From Baseline in Bone Mineral Content (BMC) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Lumbar Spine BMC Week 96 | 4.174 g | Standard Deviation 3.7068 |
| 0.5 mg/kg Asfotase Alfa | Change From Baseline in Bone Mineral Content (BMC) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Hip total BMC Week 192 | 4.725 g | Standard Deviation 6.4843 |
| 0.5 mg/kg Asfotase Alfa | Change From Baseline in Bone Mineral Content (BMC) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Hip total BMC Week 48 | 4.530 g | — |
| 0.5 mg/kg Asfotase Alfa | Change From Baseline in Bone Mineral Content (BMC) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Whole Body BMC Week 240 | 82.310 g | Standard Deviation 223.0794 |
| 0.5 mg/kg Asfotase Alfa | Change From Baseline in Bone Mineral Content (BMC) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Whole Body BMC Week 144 | 17.446 g | Standard Deviation 173.3574 |
| 0.5 mg/kg Asfotase Alfa | Change From Baseline in Bone Mineral Content (BMC) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Hip total BMC Week 240 | 6.807 g | Standard Deviation 5.7557 |
| 0.5 mg/kg Asfotase Alfa | Change From Baseline in Bone Mineral Content (BMC) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Hip total BMC Week 96 | 4.345 g | Standard Deviation 4.0466 |
| Concurrent Control | Change From Baseline in Bone Mineral Content (BMC) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Hip total BMC Week 240 | -0.673 g | Standard Deviation 0.1644 |
| Concurrent Control | Change From Baseline in Bone Mineral Content (BMC) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Hip total BMC Week 24 | 1.288 g | Standard Deviation 0.9161 |
| Concurrent Control | Change From Baseline in Bone Mineral Content (BMC) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Hip total BMC Week 48 | 2.320 g | Standard Deviation 1.399 |
| Concurrent Control | Change From Baseline in Bone Mineral Content (BMC) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Hip total BMC Week 96 | 2.907 g | Standard Deviation 2.0087 |
| Concurrent Control | Change From Baseline in Bone Mineral Content (BMC) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Hip total BMC Week 144 | 4.533 g | Standard Deviation 1.4621 |
| Concurrent Control | Change From Baseline in Bone Mineral Content (BMC) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Hip total BMC Week 192 | 2.910 g | Standard Deviation 0.291 |
| Concurrent Control | Change From Baseline in Bone Mineral Content (BMC) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Hip Total BMC Last Overall Exposure | 0.328 g | Standard Deviation 2.0062 |
| Concurrent Control | Change From Baseline in Bone Mineral Content (BMC) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Lumbar Spine BMC Week 24 | 1.432 g | Standard Deviation 1.7824 |
| Concurrent Control | Change From Baseline in Bone Mineral Content (BMC) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Lumbar Spine BMC Week 48 | 4.842 g | Standard Deviation 5.7882 |
| Concurrent Control | Change From Baseline in Bone Mineral Content (BMC) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Lumbar Spine BMC Week 96 | 7.330 g | Standard Deviation 5.6953 |
| Concurrent Control | Change From Baseline in Bone Mineral Content (BMC) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Lumbar Spine BMC Week 144 | 6.710 g | Standard Deviation 4.0174 |
| Concurrent Control | Change From Baseline in Bone Mineral Content (BMC) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Lumbar Spine BMC Week 192 | 5.197 g | Standard Deviation 5.7568 |
| Concurrent Control | Change From Baseline in Bone Mineral Content (BMC) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Lumbar Spine BMC Week 240 | 5.037 g | Standard Deviation 4.7161 |
| Concurrent Control | Change From Baseline in Bone Mineral Content (BMC) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Lumbar Spine BMC Last Overall Exposure | 6.714 g | Standard Deviation 5.1113 |
| Concurrent Control | Change From Baseline in Bone Mineral Content (BMC) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Whole Body BMC Week 24 | 237.248 g | Standard Deviation 414.0877 |
| Concurrent Control | Change From Baseline in Bone Mineral Content (BMC) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Whole Body BMC Week 48 | 30.228 g | Standard Deviation 82.4369 |
| Concurrent Control | Change From Baseline in Bone Mineral Content (BMC) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Whole Body BMC Week 96 | 98.018 g | Standard Deviation 111.9259 |
| Concurrent Control | Change From Baseline in Bone Mineral Content (BMC) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Whole Body BMC Week 144 | 92.063 g | Standard Deviation 107.9837 |
| Concurrent Control | Change From Baseline in Bone Mineral Content (BMC) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Whole Body BMC Week 192 | 50.375 g | Standard Deviation 99.6281 |
| Concurrent Control | Change From Baseline in Bone Mineral Content (BMC) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Whole Body BMC Week 240 | 40.572 g | Standard Deviation 162.1575 |
| Concurrent Control | Change From Baseline in Bone Mineral Content (BMC) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Whole Body BMC Last Overall Exposure | 82.548 g | Standard Deviation 128.7017 |
| Combined Asfotase Alfa Group | Change From Baseline in Bone Mineral Content (BMC) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Whole Body BMC Week 48 | 39.070 g | Standard Deviation 69.2934 |
| Combined Asfotase Alfa Group | Change From Baseline in Bone Mineral Content (BMC) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Lumbar Spine BMC Week 144 | 4.744 g | Standard Deviation 4.6193 |
| Combined Asfotase Alfa Group | Change From Baseline in Bone Mineral Content (BMC) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Lumbar Spine BMC Week 96 | 4.605 g | Standard Deviation 4.568 |
| Combined Asfotase Alfa Group | Change From Baseline in Bone Mineral Content (BMC) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Whole Body BMC Week 288 | -193.870 g | Standard Deviation 69.5934 |
| Combined Asfotase Alfa Group | Change From Baseline in Bone Mineral Content (BMC) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Whole Body BMC Week 96 | 46.428 g | Standard Deviation 93.5046 |
| Combined Asfotase Alfa Group | Change From Baseline in Bone Mineral Content (BMC) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Lumbar Spine BMC Week 48 | 4.597 g | Standard Deviation 4.8298 |
| Combined Asfotase Alfa Group | Change From Baseline in Bone Mineral Content (BMC) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Lumbar Spine BMC Week 24 | 2.598 g | Standard Deviation 2.2488 |
| Combined Asfotase Alfa Group | Change From Baseline in Bone Mineral Content (BMC) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Hip total BMC Week 48 | 2.495 g | Standard Deviation 1.5438 |
| Combined Asfotase Alfa Group | Change From Baseline in Bone Mineral Content (BMC) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Whole Body BMC Week 144 | 15.307 g | Standard Deviation 138.3534 |
| Combined Asfotase Alfa Group | Change From Baseline in Bone Mineral Content (BMC) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Hip Total BMC Last Overall Exposure | 1.512 g | Standard Deviation 4.0224 |
| Combined Asfotase Alfa Group | Change From Baseline in Bone Mineral Content (BMC) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Hip Total BMC Week 288 | -2.780 g | — |
| Combined Asfotase Alfa Group | Change From Baseline in Bone Mineral Content (BMC) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Hip total BMC Week 24 | -0.787 g | Standard Deviation 5.5411 |
| Combined Asfotase Alfa Group | Change From Baseline in Bone Mineral Content (BMC) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Whole Body BMC Week 192 | -20.599 g | Standard Deviation 151.5153 |
| Combined Asfotase Alfa Group | Change From Baseline in Bone Mineral Content (BMC) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Hip total BMC Week 240 | 2.438 g | Standard Deviation 4.8626 |
| Combined Asfotase Alfa Group | Change From Baseline in Bone Mineral Content (BMC) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Hip total BMC Week 192 | 3.310 g | Standard Deviation 4.3124 |
| Combined Asfotase Alfa Group | Change From Baseline in Bone Mineral Content (BMC) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Whole Body BMC Last Overall Exposure | -19.063 g | Standard Deviation 188.0498 |
| Combined Asfotase Alfa Group | Change From Baseline in Bone Mineral Content (BMC) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Whole Body BMC Week 240 | 0.231 g | Standard Deviation 172.0218 |
| Combined Asfotase Alfa Group | Change From Baseline in Bone Mineral Content (BMC) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Lumbar Spine BMC Last Overall Exposure | 5.256 g | Standard Deviation 9.5103 |
| Combined Asfotase Alfa Group | Change From Baseline in Bone Mineral Content (BMC) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Lumbar Spine BMC Week 288 | 13.705 g | Standard Deviation 10.1894 |
| Combined Asfotase Alfa Group | Change From Baseline in Bone Mineral Content (BMC) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Hip total BMC Week 144 | 3.866 g | Standard Deviation 3.7577 |
| Combined Asfotase Alfa Group | Change From Baseline in Bone Mineral Content (BMC) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Whole Body BMC Week 24 | 4.514 g | Standard Deviation 43.5228 |
| Combined Asfotase Alfa Group | Change From Baseline in Bone Mineral Content (BMC) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Lumbar Spine BMC Week 240 | 3.925 g | Standard Deviation 10.2539 |
| Combined Asfotase Alfa Group | Change From Baseline in Bone Mineral Content (BMC) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Lumbar Spine BMC Week 192 | 4.434 g | Standard Deviation 9.9797 |
| Combined Asfotase Alfa Group | Change From Baseline in Bone Mineral Content (BMC) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Hip total BMC Week 96 | 2.403 g | Standard Deviation 3.1702 |
Comparison: Hip Total BMC Change from Baseline to Week 24p-value: 0.330195% CI: [-3.32, 1.78]Wilcoxon rank-sum
Comparison: Lumbar Spine BMC Change from Baseline to Week 24p-value: 0.382795% CI: [-1.36, 3.12]Wilcoxon rank-sum
Comparison: Whole Body BMC Change from Baseline to Week 24p-value: 0.048595% CI: [-917.44, -1.74]Wilcoxon rank-sum
Secondary
Change From Baseline in Bone Mineral Density (BMD) as Measured by Dual-energy X-ray Absorptiometry (DXA)
A DXA scan was performed to evaluate bone bone mineral density (BMD) of the spine, hip, and whole body during the primary (first 24 weeks) and extension treatment periods (up to 288 weeks).
Time frame: Baseline, every 24 weeks through Week 96, then every 48 weeks until Week 288.
Population: Full analysis set (intent-to-treat, all randomized patients)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 0.3 mg/kg Asfotase Alfa | Change From Baseline in Bone Mineral Density (BMD) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Hip total BMD Week 144 | 0.0340 g/cm2 | Standard Deviation 0.02524 |
| 0.3 mg/kg Asfotase Alfa | Change From Baseline in Bone Mineral Density (BMD) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Lumbar Spine BMD Week 240 | 0.0750 g/cm2 | Standard Deviation 0.14168 |
| 0.3 mg/kg Asfotase Alfa | Change From Baseline in Bone Mineral Density (BMD) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Hip total BMD Week 24 | 0.0477 g/cm2 | Standard Deviation 0.0771 |
| 0.3 mg/kg Asfotase Alfa | Change From Baseline in Bone Mineral Density (BMD) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Hip total BMD Last Overall Exposure | -0.0115 g/cm2 | Standard Deviation 0.03899 |
| 0.3 mg/kg Asfotase Alfa | Change From Baseline in Bone Mineral Density (BMD) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Whole Body BMD Week 24 | -0.0003 g/cm2 | Standard Deviation 0.01788 |
| 0.3 mg/kg Asfotase Alfa | Change From Baseline in Bone Mineral Density (BMD) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Hip total BMD Week 48 | 0.0190 g/cm2 | — |
| 0.3 mg/kg Asfotase Alfa | Change From Baseline in Bone Mineral Density (BMD) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Lumbar Spine BMD Week 288 | 0.1860 g/cm2 | — |
| 0.3 mg/kg Asfotase Alfa | Change From Baseline in Bone Mineral Density (BMD) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Lumbar Spine BMD Week 24 | 0.0269 g/cm2 | Standard Deviation 0.02113 |
| 0.3 mg/kg Asfotase Alfa | Change From Baseline in Bone Mineral Density (BMD) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Whole Body BMD Week 144 | -0.0250 g/cm2 | Standard Deviation 0.03662 |
| 0.3 mg/kg Asfotase Alfa | Change From Baseline in Bone Mineral Density (BMD) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Whole Body BMD Week 192 | -0.0532 g/cm2 | Standard Deviation 0.02477 |
| 0.3 mg/kg Asfotase Alfa | Change From Baseline in Bone Mineral Density (BMD) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Hip total BMD Week 96 | 0.0003 g/cm2 | Standard Deviation 0.00532 |
| 0.3 mg/kg Asfotase Alfa | Change From Baseline in Bone Mineral Density (BMD) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Lumbar Spine BMD Week 48 | 0.0480 g/cm2 | — |
| 0.3 mg/kg Asfotase Alfa | Change From Baseline in Bone Mineral Density (BMD) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Hip total BMD Week 192 | 0.0135 g/cm2 | Standard Deviation 0.00919 |
| 0.3 mg/kg Asfotase Alfa | Change From Baseline in Bone Mineral Density (BMD) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Whole Body BMD Week 48 | 0.0050 g/cm2 | — |
| 0.3 mg/kg Asfotase Alfa | Change From Baseline in Bone Mineral Density (BMD) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Whole Body BMD Week 96 | -0.0103 g/cm2 | Standard Deviation 0.03523 |
| 0.3 mg/kg Asfotase Alfa | Change From Baseline in Bone Mineral Density (BMD) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Lumbar Spine BMD Week 96 | 0.0414 g/cm2 | Standard Deviation 0.0523 |
| 0.3 mg/kg Asfotase Alfa | Change From Baseline in Bone Mineral Density (BMD) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Whole Body BMD Last Overall Exposure | -0.0501 g/cm2 | Standard Deviation 0.0736 |
| 0.3 mg/kg Asfotase Alfa | Change From Baseline in Bone Mineral Density (BMD) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Whole Body BMD Week 288 | -0.1140 g/cm2 | — |
| 0.3 mg/kg Asfotase Alfa | Change From Baseline in Bone Mineral Density (BMD) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Hip total BMD Week 240 | 0.0115 g/cm2 | Standard Deviation 0.02192 |
| 0.3 mg/kg Asfotase Alfa | Change From Baseline in Bone Mineral Density (BMD) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Lumbar Spine BMD Week 144 | 0.0200 g/cm2 | Standard Deviation 0.06257 |
| 0.3 mg/kg Asfotase Alfa | Change From Baseline in Bone Mineral Density (BMD) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Lumbar Spine BMD Last Overall Exposure | 0.0737 g/cm2 | Standard Deviation 0.11346 |
| 0.3 mg/kg Asfotase Alfa | Change From Baseline in Bone Mineral Density (BMD) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Whole Body BMD Week 240 | -0.0426 g/cm2 | Standard Deviation 0.05601 |
| 0.3 mg/kg Asfotase Alfa | Change From Baseline in Bone Mineral Density (BMD) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Lumbar Spine BMD Week 192 | 0.0554 g/cm2 | Standard Deviation 0.1322 |
| 0.5 mg/kg Asfotase Alfa | Change From Baseline in Bone Mineral Density (BMD) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Lumbar Spine BMD Week 144 | 0.0850 g/cm2 | Standard Deviation 0.05323 |
| 0.5 mg/kg Asfotase Alfa | Change From Baseline in Bone Mineral Density (BMD) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Whole Body BMD Week 240 | -0.0122 g/cm2 | Standard Deviation 0.0861 |
| 0.5 mg/kg Asfotase Alfa | Change From Baseline in Bone Mineral Density (BMD) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Lumbar Spine BMD Week 192 | 0.0766 g/cm2 | Standard Deviation 0.0418 |
| 0.5 mg/kg Asfotase Alfa | Change From Baseline in Bone Mineral Density (BMD) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Lumbar Spine BMD Week 240 | 0.0455 g/cm2 | Standard Deviation 0.04107 |
| 0.5 mg/kg Asfotase Alfa | Change From Baseline in Bone Mineral Density (BMD) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Hip total BMD Week 240 | 0.1137 g/cm2 | Standard Deviation 0.05701 |
| 0.5 mg/kg Asfotase Alfa | Change From Baseline in Bone Mineral Density (BMD) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Hip total BMD Week 144 | 0.0923 g/cm2 | Standard Deviation 0.07682 |
| 0.5 mg/kg Asfotase Alfa | Change From Baseline in Bone Mineral Density (BMD) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Lumbar Spine BMD Week 288 | 0.0700 g/cm2 | — |
| 0.5 mg/kg Asfotase Alfa | Change From Baseline in Bone Mineral Density (BMD) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Lumbar Spine BMD Last Overall Exposure | 0.0492 g/cm2 | Standard Deviation 0.04649 |
| 0.5 mg/kg Asfotase Alfa | Change From Baseline in Bone Mineral Density (BMD) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Whole Body BMD Week 288 | -0.0710 g/cm2 | — |
| 0.5 mg/kg Asfotase Alfa | Change From Baseline in Bone Mineral Density (BMD) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Whole Body BMD Week 24 | -0.0122 g/cm2 | Standard Deviation 0.01055 |
| 0.5 mg/kg Asfotase Alfa | Change From Baseline in Bone Mineral Density (BMD) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Whole Body BMD Week 48 | 0.0090 g/cm2 | — |
| 0.5 mg/kg Asfotase Alfa | Change From Baseline in Bone Mineral Density (BMD) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Whole Body BMD Week 144 | -0.0278 g/cm2 | Standard Deviation 0.05823 |
| 0.5 mg/kg Asfotase Alfa | Change From Baseline in Bone Mineral Density (BMD) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Whole Body BMD Last Overall Exposure | -0.0298 g/cm2 | Standard Deviation 0.08785 |
| 0.5 mg/kg Asfotase Alfa | Change From Baseline in Bone Mineral Density (BMD) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Hip total BMD Week 48 | 0.0240 g/cm2 | — |
| 0.5 mg/kg Asfotase Alfa | Change From Baseline in Bone Mineral Density (BMD) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Hip total BMD Week 288 | -0.0200 g/cm2 | — |
| 0.5 mg/kg Asfotase Alfa | Change From Baseline in Bone Mineral Density (BMD) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Whole Body BMD Week 96 | -0.0100 g/cm2 | Standard Deviation 0.04136 |
| 0.5 mg/kg Asfotase Alfa | Change From Baseline in Bone Mineral Density (BMD) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Hip total BMD Last Overall Exposure | 0.0658 g/cm2 | Standard Deviation 0.07776 |
| 0.5 mg/kg Asfotase Alfa | Change From Baseline in Bone Mineral Density (BMD) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Hip total BMD Week 24 | 0.0094 g/cm2 | Standard Deviation 0.02441 |
| 0.5 mg/kg Asfotase Alfa | Change From Baseline in Bone Mineral Density (BMD) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Lumbar Spine BMD Week 24 | 0.0272 g/cm2 | Standard Deviation 0.01492 |
| 0.5 mg/kg Asfotase Alfa | Change From Baseline in Bone Mineral Density (BMD) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Lumbar Spine BMD Week 48 | 0.0590 g/cm2 | — |
| 0.5 mg/kg Asfotase Alfa | Change From Baseline in Bone Mineral Density (BMD) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Whole Body BMD Week 192 | -0.0220 g/cm2 | Standard Deviation 0.07088 |
| 0.5 mg/kg Asfotase Alfa | Change From Baseline in Bone Mineral Density (BMD) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Hip total BMD Week 96 | 0.0780 g/cm2 | Standard Deviation 0.06703 |
| 0.5 mg/kg Asfotase Alfa | Change From Baseline in Bone Mineral Density (BMD) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Lumbar Spine BMD Week 96 | 0.0554 g/cm2 | Standard Deviation 0.04271 |
| 0.5 mg/kg Asfotase Alfa | Change From Baseline in Bone Mineral Density (BMD) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Hip total BMD Week 192 | 0.0983 g/cm2 | Standard Deviation 0.10856 |
| Concurrent Control | Change From Baseline in Bone Mineral Density (BMD) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Hip total BMD Week 96 | 0.0480 g/cm2 | Standard Deviation 0.04943 |
| Concurrent Control | Change From Baseline in Bone Mineral Density (BMD) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Whole Body BMD Week 96 | 0.0230 g/cm2 | Standard Deviation 0.04872 |
| Concurrent Control | Change From Baseline in Bone Mineral Density (BMD) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Hip total BMD Week 192 | 0.0563 g/cm2 | Standard Deviation 0.071 |
| Concurrent Control | Change From Baseline in Bone Mineral Density (BMD) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Whole Body BMD Week 144 | -0.0060 g/cm2 | Standard Deviation 0.04721 |
| Concurrent Control | Change From Baseline in Bone Mineral Density (BMD) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Whole Body BMD Week 192 | -0.0212 g/cm2 | Standard Deviation 0.06209 |
| Concurrent Control | Change From Baseline in Bone Mineral Density (BMD) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Whole Body BMD Week 240 | -0.0493 g/cm2 | Standard Deviation 0.06965 |
| Concurrent Control | Change From Baseline in Bone Mineral Density (BMD) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Hip total BMD Week 240 | -0.0073 g/cm2 | Standard Deviation 0.06178 |
| Concurrent Control | Change From Baseline in Bone Mineral Density (BMD) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Whole Body BMD Last Overall Exposure | -0.0224 g/cm2 | Standard Deviation 0.05773 |
| Concurrent Control | Change From Baseline in Bone Mineral Density (BMD) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Hip total BMD Week 48 | 0.0590 g/cm2 | Standard Deviation 0.04109 |
| Concurrent Control | Change From Baseline in Bone Mineral Density (BMD) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Hip total BMD Last Overall Exposure | 0.0207 g/cm2 | Standard Deviation 0.07549 |
| Concurrent Control | Change From Baseline in Bone Mineral Density (BMD) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Lumbar Spine BMD Week 24 | 0.0098 g/cm2 | Standard Deviation 0.02475 |
| Concurrent Control | Change From Baseline in Bone Mineral Density (BMD) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Lumbar Spine BMD Week 48 | 0.0914 g/cm2 | Standard Deviation 0.05647 |
| Concurrent Control | Change From Baseline in Bone Mineral Density (BMD) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Lumbar Spine BMD Week 96 | 0.1158 g/cm2 | Standard Deviation 0.0806 |
| Concurrent Control | Change From Baseline in Bone Mineral Density (BMD) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Whole Body BMD Week 48 | 0.0178 g/cm2 | Standard Deviation 0.05277 |
| Concurrent Control | Change From Baseline in Bone Mineral Density (BMD) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Lumbar Spine BMD Week 144 | 0.1138 g/cm2 | Standard Deviation 0.05734 |
| Concurrent Control | Change From Baseline in Bone Mineral Density (BMD) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Hip total BMD Week 24 | 0.0195 g/cm2 | Standard Deviation 0.01642 |
| Concurrent Control | Change From Baseline in Bone Mineral Density (BMD) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Lumbar Spine BMD Week 192 | 0.1123 g/cm2 | Standard Deviation 0.05197 |
| Concurrent Control | Change From Baseline in Bone Mineral Density (BMD) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Lumbar Spine BMD Week 240 | 0.1027 g/cm2 | Standard Deviation 0.04786 |
| Concurrent Control | Change From Baseline in Bone Mineral Density (BMD) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Hip total BMD Week 144 | 0.0933 g/cm2 | Standard Deviation 0.0415 |
| Concurrent Control | Change From Baseline in Bone Mineral Density (BMD) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Lumbar Spine BMD Last Overall Exposure | 0.1194 g/cm2 | Standard Deviation 0.04999 |
| Concurrent Control | Change From Baseline in Bone Mineral Density (BMD) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Whole Body BMD Week 24 | 0.0206 g/cm2 | Standard Deviation 0.03173 |
| Combined Asfotase Alfa Group | Change From Baseline in Bone Mineral Density (BMD) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Whole Body BMD Last Overall Exposure | -0.0360 g/cm2 | Standard Deviation 0.07036 |
| Combined Asfotase Alfa Group | Change From Baseline in Bone Mineral Density (BMD) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Hip total BMD Week 24 | 0.0251 g/cm2 | Standard Deviation 0.05361 |
| Combined Asfotase Alfa Group | Change From Baseline in Bone Mineral Density (BMD) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Hip total BMD Week 48 | 0.0465 g/cm2 | Standard Deviation 0.03729 |
| Combined Asfotase Alfa Group | Change From Baseline in Bone Mineral Density (BMD) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Hip total BMD Week 96 | 0.0415 g/cm2 | Standard Deviation 0.05542 |
| Combined Asfotase Alfa Group | Change From Baseline in Bone Mineral Density (BMD) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Hip total BMD Week 144 | 0.0751 g/cm2 | Standard Deviation 0.05741 |
| Combined Asfotase Alfa Group | Change From Baseline in Bone Mineral Density (BMD) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Hip total BMD Week 192 | 0.0654 g/cm2 | Standard Deviation 0.08327 |
| Combined Asfotase Alfa Group | Change From Baseline in Bone Mineral Density (BMD) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Hip total BMD Week 240 | 0.0428 g/cm2 | Standard Deviation 0.07481 |
| Combined Asfotase Alfa Group | Change From Baseline in Bone Mineral Density (BMD) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Hip total BMD Week 288 | -0.0200 g/cm2 | — |
| Combined Asfotase Alfa Group | Change From Baseline in Bone Mineral Density (BMD) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Hip total BMD Last Overall Exposure | 0.0282 g/cm2 | Standard Deviation 0.07038 |
| Combined Asfotase Alfa Group | Change From Baseline in Bone Mineral Density (BMD) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Lumbar Spine BMD Week 24 | 0.0270 g/cm2 | Standard Deviation 0.01802 |
| Combined Asfotase Alfa Group | Change From Baseline in Bone Mineral Density (BMD) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Lumbar Spine BMD Week 48 | 0.0806 g/cm2 | Standard Deviation 0.04978 |
| Combined Asfotase Alfa Group | Change From Baseline in Bone Mineral Density (BMD) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Lumbar Spine BMD Week 96 | 0.0644 g/cm2 | Standard Deviation 0.0621 |
| Combined Asfotase Alfa Group | Change From Baseline in Bone Mineral Density (BMD) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Lumbar Spine BMD Week 144 | 0.0700 g/cm2 | Standard Deviation 0.06688 |
| Combined Asfotase Alfa Group | Change From Baseline in Bone Mineral Density (BMD) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Lumbar Spine BMD Week 192 | 0.0792 g/cm2 | Standard Deviation 0.08423 |
| Combined Asfotase Alfa Group | Change From Baseline in Bone Mineral Density (BMD) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Lumbar Spine BMD Week 240 | 0.0745 g/cm2 | Standard Deviation 0.09073 |
| Combined Asfotase Alfa Group | Change From Baseline in Bone Mineral Density (BMD) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Lumbar Spine BMD Week 288 | 0.1280 g/cm2 | Standard Deviation 0.08202 |
| Combined Asfotase Alfa Group | Change From Baseline in Bone Mineral Density (BMD) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Lumbar Spine BMD Last Overall Exposure | 0.0799 g/cm2 | Standard Deviation 0.08241 |
| Combined Asfotase Alfa Group | Change From Baseline in Bone Mineral Density (BMD) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Whole Body BMD Week 24 | -0.0052 g/cm2 | Standard Deviation 0.01589 |
| Combined Asfotase Alfa Group | Change From Baseline in Bone Mineral Density (BMD) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Whole Body BMD Week 48 | 0.0147 g/cm2 | Standard Deviation 0.04342 |
| Combined Asfotase Alfa Group | Change From Baseline in Bone Mineral Density (BMD) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Whole Body BMD Week 96 | -0.0019 g/cm2 | Standard Deviation 0.04059 |
| Combined Asfotase Alfa Group | Change From Baseline in Bone Mineral Density (BMD) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Whole Body BMD Week 144 | -0.0206 g/cm2 | Standard Deviation 0.04542 |
| Combined Asfotase Alfa Group | Change From Baseline in Bone Mineral Density (BMD) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Whole Body BMD Week 192 | -0.0329 g/cm2 | Standard Deviation 0.05358 |
| Combined Asfotase Alfa Group | Change From Baseline in Bone Mineral Density (BMD) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Whole Body BMD Week 240 | -0.0353 g/cm2 | Standard Deviation 0.06615 |
| Combined Asfotase Alfa Group | Change From Baseline in Bone Mineral Density (BMD) as Measured by Dual-energy X-ray Absorptiometry (DXA) | Whole Body BMD Week 288 | -0.0925 g/cm2 | Standard Deviation 0.03041 |
Comparison: Hip Total Change from Baseline to Week 24p-value: 0.735795% CI: [-0.04, 0.039]Wilcoxon rank-sum
Comparison: Lumbar Spine BMD Change from Baseline to Week 24p-value: 0.243995% CI: [-0.009, 0.041]Wilcoxon rank-sum
Comparison: Whole Body BMD Change from Baseline to Week 24p-value: 0.122295% CI: [-0.059, 0.012]Wilcoxon rank-sum
Secondary
Change From Baseline in HPP-related Osteomalacia as Measured by Trans-iliac Crest Bone Biopsy: Mineralization Lag Time
A trans-iliac crest bone biopsy was performed to quantify changes from Baseline in histomorphometric parameters relevant for evaluation of osteomalacia severity, including Mineralization Lag Time (days). The difference in time under observation between asfotase alfa groups (Week 48) and control group (Week 24) resulted from study design, ie, control subjects transitioned to active treatment after the Week 24 visit.
Time frame: Baseline, Week 24 (Control group), and Week 48 (Asfotase alfa groups).
Population: Full analysis set (intent-to-treat, all randomized patients)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 0.3 mg/kg Asfotase Alfa | Change From Baseline in HPP-related Osteomalacia as Measured by Trans-iliac Crest Bone Biopsy: Mineralization Lag Time | -908.255 days | Standard Deviation 1313.6158 |
| 0.5 mg/kg Asfotase Alfa | Change From Baseline in HPP-related Osteomalacia as Measured by Trans-iliac Crest Bone Biopsy: Mineralization Lag Time | -126.946 days | Standard Deviation 142.2929 |
| Concurrent Control | Change From Baseline in HPP-related Osteomalacia as Measured by Trans-iliac Crest Bone Biopsy: Mineralization Lag Time | 78.296 days | Standard Deviation 167.0895 |
| Combined Asfotase Alfa Group | Change From Baseline in HPP-related Osteomalacia as Measured by Trans-iliac Crest Bone Biopsy: Mineralization Lag Time | -474.195 days | Standard Deviation 909.2779 |
Secondary
Change From Baseline in HPP-related Osteomalacia as Measured by Trans-iliac Crest Bone Biopsy: Osteoid Thickness
A trans-iliac crest bone biopsy was performed to quantify changes from Baseline in histomorphometric parameters relevant for evaluation of osteomalacia severity, including Osteoid Thickness (um). The difference in time under observation between asfotase alfa groups (Week 48) and control group (Week 24) resulted from study design, ie, control subjects transitioned to active treatment after the Week 24 visit.
Time frame: Baseline, Week 24 (Control group), and Week 48 (Asfotase alfa groups).
Population: Full analysis set (intent-to-treat, all randomized patients)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 0.3 mg/kg Asfotase Alfa | Change From Baseline in HPP-related Osteomalacia as Measured by Trans-iliac Crest Bone Biopsy: Osteoid Thickness | -0.013 um | Standard Deviation 3.6333 |
| 0.5 mg/kg Asfotase Alfa | Change From Baseline in HPP-related Osteomalacia as Measured by Trans-iliac Crest Bone Biopsy: Osteoid Thickness | -1.516 um | Standard Deviation 2.3556 |
| Concurrent Control | Change From Baseline in HPP-related Osteomalacia as Measured by Trans-iliac Crest Bone Biopsy: Osteoid Thickness | -1.132 um | Standard Deviation 6.0884 |
| Combined Asfotase Alfa Group | Change From Baseline in HPP-related Osteomalacia as Measured by Trans-iliac Crest Bone Biopsy: Osteoid Thickness | -0.764 um | Standard Deviation 3.0229 |
Secondary
Change From Baseline in HPP-related Osteomalacia as Measured by Trans-iliac Crest Bone Biopsy: Osteoid Volume/Bone Volume
A trans-iliac crest bone biopsy was performed to quantify changes from Baseline in histomorphometric parameters relevant for evaluation of osteomalacia severity, including Osteoid Volume/Bone Volume (%). The difference in time under observation between asfotase alfa groups (Week 48) and control group (Week 24) resulted from study design, ie, control subjects transitioned to active treatment after the Week 24 visit.
Time frame: Baseline, Week 24 (Control group), and Week 48 (Asfotase alfa groups).
Population: Full analysis set (intent-to-treat, all randomized patients)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 0.3 mg/kg Asfotase Alfa | Change From Baseline in HPP-related Osteomalacia as Measured by Trans-iliac Crest Bone Biopsy: Osteoid Volume/Bone Volume | 1.213 percentage of volume | Standard Deviation 3.2488 |
| 0.5 mg/kg Asfotase Alfa | Change From Baseline in HPP-related Osteomalacia as Measured by Trans-iliac Crest Bone Biopsy: Osteoid Volume/Bone Volume | -2.845 percentage of volume | Standard Deviation 2.3769 |
| Concurrent Control | Change From Baseline in HPP-related Osteomalacia as Measured by Trans-iliac Crest Bone Biopsy: Osteoid Volume/Bone Volume | 0.200 percentage of volume | Standard Deviation 4.7679 |
| Combined Asfotase Alfa Group | Change From Baseline in HPP-related Osteomalacia as Measured by Trans-iliac Crest Bone Biopsy: Osteoid Volume/Bone Volume | -0.816 percentage of volume | Standard Deviation 3.4434 |
Secondary
Change in Walking Ability as Measured by the Six-Minute Walk Test (6MWT)
The patient was instructed to walk the length of a pre-measured hallway for 6 minutes. The primary measurement was distance walked (in meters).
Time frame: Baseline, Week 24 (primary treatment period) and up to 288 weeks of asfotase alfa exposure
Population: Full analysis set (intent-to-treat, all randomized patients). Among the 6 control subjects, only 4 had both a Baseline and Week 24 value.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 0.3 mg/kg Asfotase Alfa | Change in Walking Ability as Measured by the Six-Minute Walk Test (6MWT) | Change from Baseline to Week 24 | 64.7 meters | Standard Deviation 73.04 |
| 0.3 mg/kg Asfotase Alfa | Change in Walking Ability as Measured by the Six-Minute Walk Test (6MWT) | Change from Baseline Last Overall Exposure | 89.4 meters | Standard Deviation 81.32 |
| 0.5 mg/kg Asfotase Alfa | Change in Walking Ability as Measured by the Six-Minute Walk Test (6MWT) | Change from Baseline Last Overall Exposure | 2.2 meters | Standard Deviation 121.79 |
| 0.5 mg/kg Asfotase Alfa | Change in Walking Ability as Measured by the Six-Minute Walk Test (6MWT) | Change from Baseline to Week 24 | 43.5 meters | Standard Deviation 43.18 |
| Concurrent Control | Change in Walking Ability as Measured by the Six-Minute Walk Test (6MWT) | Change from Baseline to Week 24 | 13.5 meters | Standard Deviation 69.77 |
| Concurrent Control | Change in Walking Ability as Measured by the Six-Minute Walk Test (6MWT) | Change from Baseline Last Overall Exposure | 74.4 meters | Standard Deviation 107.4 |
| Combined Asfotase Alfa Group | Change in Walking Ability as Measured by the Six-Minute Walk Test (6MWT) | Change from Baseline to Week 24 | 54.9 meters | Standard Deviation 59.71 |
| Combined Asfotase Alfa Group | Change in Walking Ability as Measured by the Six-Minute Walk Test (6MWT) | Change from Baseline Last Overall Exposure | 56.2 meters | Standard Deviation 104.85 |
Comparison: Week 24 Change from Baselinep-value: 0.130395% CI: [-73, 114]Wilcoxon rank-sum