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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
19
Cohort 1: Daily SC injections of 0.3 mg/kg asfotase alfa (total of 2.1 mg/kg/week)
Cohort 2: Daily SC injections of 0.5 mg/kg Asfotase Alfa (3.5 mg/kg/week total)
Shriner's Hospital for Children
St Louis, Missouri, United States
Duke University Medical Center
Durham, North Carolina, United States
Health Sciences Centre Winnipeg, University of Manitoba
Winnipeg, Manitoba, Canada
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
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
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
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.
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.
Change in Walking Ability as Measured by the Six-Minute Walk Test (6MWT)
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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
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).
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).
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).