Bone Disease, Hypophosphatasia
Conditions
Keywords
HPP, Soft Bones, low Alkaline Phosphatase, genetic metabolic disorder, alkaline phosphatase, tissue non-specific alkaline phosphatase, rickets, osteomalacia
Brief summary
The purpose of this study is to characterize the natural history of HPP in patients with Juvenile-onset HPP who served as historical controls in ENB-006-09.
Detailed description
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 no approved disease-modifying treatments for patients with this disease. There is also limited data available on the natural course of this disease over time, particularly in patients with the juvenile-onset form.
Interventions
BIOLOGICALRetrospective Case Only
Sponsors
Alexion Pharmaceuticals, Inc.
Study design
Observational model
OTHER
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
5 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Documented informed consent/assent prior to video collection and data abstraction. * Documented informed consent/assent in Study ALX-HPP-502. * Patients with juvenile-onset HPP and was selected as a historical-control for Study ENB-006-09. * Patients with at least 2 videos of basic mobility that were recorded at 2 different clinic visits when the patient was ≥5 to ≤15 ye
Exclusion criteria
* There are no
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Modified Performance-Oriented Mobility Assessment-Gait Subtest (MPOMA-G) - Change From Baseline to Last Overall | The earliest available MPOMA-G score that was assessed within the period of patients' aged 5 to 15 years, inclusive. | The MPOMA-G is a 5-component assessment that is used to evaluate gait performance. The first component has 4 sub-components. For 2 components and 2 sub-components, scores of 0 or 1 are assigned while scores of 0, 1 or 2 are assigned to the rest of the 2 components and 2 sub-components based on type of ambulation pattern observed. The maximum total score of 12 points = no impairment and 0 points = worst impairment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Performance-Oriented Mobility Assessment-Gait Subtest (POMA-G) - Change From Baseline to Last Overall | The earliest available MPOMA-G score that was assessed within the period of patients' aged 5 to 15 years, inclusive. | The POMA-G is a 7-component assessment that is used to evaluate gait performance. The second component has 4 sub-components. Scores of 0, 1 or 2 are assigned to 2 components while scores of 0 or 1 are assigned to the rest of the 4 components and 4 sub-components based on type of ambulation pattern observed. The maximum total score of 12 points = no impairment and 0 points = worst impairment. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Retrospective Observational Patients diagnosed with juvenile-onset hypophosphatasia (HPP) \[ie, documented onset of first signs/symptoms of HPP at ≥ 6 months to \< 18 years of age\]. | 6 |
| Total | 6 |
Baseline characteristics
| Characteristic | Retrospective Observational |
|---|---|
| Age, Customized | 28.2 months STANDARD_DEVIATION 10.6 |
| Deceased/Alive Status - Alive | 6 participants |
| Deceased/Alive Status - Deceased | 0 participants |
| Modified Performance-Oriented Mobility Assessment - Gait subtest (MPOMA-G) | 6.00 units on a scale |
| Race/Ethnicity, Customized White, Hispanic or Latino | 2 participants |
| Race/Ethnicity, Customized White, Not Hispanic or Latino | 4 participants |
| Region of Enrollment United States | 6 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 |
Outcome results
Primary
Modified Performance-Oriented Mobility Assessment-Gait Subtest (MPOMA-G) - Change From Baseline to Last Overall
The MPOMA-G is a 5-component assessment that is used to evaluate gait performance. The first component has 4 sub-components. For 2 components and 2 sub-components, scores of 0 or 1 are assigned while scores of 0, 1 or 2 are assigned to the rest of the 2 components and 2 sub-components based on type of ambulation pattern observed. The maximum total score of 12 points = no impairment and 0 points = worst impairment.
Time frame: The earliest available MPOMA-G score that was assessed within the period of patients' aged 5 to 15 years, inclusive.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Retrospective Observational | Modified Performance-Oriented Mobility Assessment-Gait Subtest (MPOMA-G) - Change From Baseline to Last Overall | 1.50 units on a scale |
Comparison: Videos were reviewed and scored by 3 independent raters who were masked to patient identifiers and the clinic visits and dates when the videos were recorded. Each rater scored the individual components required for the calculation of the total MPOMA-G score for each evaluable patient video. The median of the scores across the 3 raters was obtained for each individual component and summed to generate the median MPOMA-G score used in the analyses.p-value: 0.0625Sign test
Secondary
Performance-Oriented Mobility Assessment-Gait Subtest (POMA-G) - Change From Baseline to Last Overall
The POMA-G is a 7-component assessment that is used to evaluate gait performance. The second component has 4 sub-components. Scores of 0, 1 or 2 are assigned to 2 components while scores of 0 or 1 are assigned to the rest of the 4 components and 4 sub-components based on type of ambulation pattern observed. The maximum total score of 12 points = no impairment and 0 points = worst impairment.
Time frame: The earliest available MPOMA-G score that was assessed within the period of patients' aged 5 to 15 years, inclusive.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Retrospective Observational | Performance-Oriented Mobility Assessment-Gait Subtest (POMA-G) - Change From Baseline to Last Overall | 1.50 units on a scale |
Comparison: Videos were reviewed and scored by 3 independent raters who were masked to patient identifiers and the clinic visits and dates when the videos were recorded. Each rater scored the individual components required for the calculation of the total POMA-G score for each evaluable patient video. The median of the scores across the 3 raters was obtained for each individual component and summed to generate the median POMA-G score used in the analyses.p-value: 0.125Sign test