Hypophosphatasia (HPP)
Conditions
Keywords
Hypophosphatasia, HPP, Bone disease, Soft bones, Low alkaline phosphatase, Genetic metabolic disorder, Alkaline phosphatase, Tissue non-specific alkaline phosphatase, Rickets, Osteomalacia
Brief summary
This study aims to characterize the natural history of patients with severe perinatal or infantile onset HPP.
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
None listed
Sponsors
Alexion Pharmaceuticals, Inc.
Study design
Observational model
COHORT
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* Parent(s) or legal guardian(s) must provide written informed consent prior to data abstraction, unless all of the following apply: * The patient is deceased; AND * The responsible IRB/IEC/REB does not require informed consent per a review of their documented local policies for collecting retrospective data on patients who are deceased; AND * Written confirmation is received from the responsible IRB/IEC/REB confirming that the abstracted data can be analyzed and used to support regulatory filings by the Sponsor * Patient must have a documented diagnosis of HPP as indicated by 1 or more of the following: * Documented ALPL gene mutation(s) * Serum alkaline phosphatase (ALP) below the age-adjusted normal range and either plasma pyridoxal 5'-phosphate (PLP) or urinary phosphoethanolamine (PEA) above the upper limit of normal * Serum ALP below the age-adjusted normal range and HPP-related radiographic abnormalities on X-ray * Patient must have onset of signs of HPP prior to 6 months of age and have documentation of 1 or more of the following characteristics of perinatal and infantile HPP: * Respiratory compromise (up to and including respiratory failure) requiring institution of respiratory support measure(s), requiring medication(s) for management of symptom(s), and/or associated with other respiratory complications (e.g., pneumonia(s), respiratory tract infection(s)) * Pyridoxine (vitamin B6)-responsive seizures * Rachitic chest deformity
Exclusion criteria
Patients will be excluded from study participation if they have 1 or more of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Survival | Retrospective data collected on or before the data of abstraction. | Overall survival is defined as the time from birth to time of death. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Invasive Ventilator-free Survival Time | Retrospective data collected on or before the date of abstraction. | Invasive ventilator-free survival is defined as the time during which the patient is alive and not invasively ventilated. For the purpose of this study, invasive ventilation is defined as mechanical ventilation via intubation of trachaeostomy. |
Countries
Australia, Canada, Germany, Spain, Taiwan, United Kingdom, United States
Participant flow
Recruitment details
Patients were enrolled between Sept 2012 and Apr 2013. 65 patients were screened and 48 were enrolled at 12 sites in 7 countries. Patients were recruited from investigational sites established at academic research and medical centers known to diagnose and/or treat patients with HPP. Both living and deceased patients were considered to partricipate.
Participants by arm
| Arm | Count |
|---|---|
| Retrospective Observational Patients with severe perinatal and/or infantile onset HPP (ie, where signs of the disease are present before 6 months of age). | 48 |
| Total | 48 |
Baseline characteristics
| Characteristic | Retrospective Observational |
|---|---|
| Age, Continuous | 506.9 weeks STANDARD_DEVIATION 319.24 |
| Age, Customized <=18 years | 10 weeks |
| Age, Customized >=65 years | 0 weeks |
| Age, Customized Between 18 and 65 years | 3 weeks |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 41 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 6 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) White | 40 Participants |
| Region of Enrollment Australia | 2 participants |
| Region of Enrollment Canada | 11 participants |
| Region of Enrollment Germany | 6 participants |
| Region of Enrollment Spain | 1 participants |
| Region of Enrollment Switzerland | 1 participants |
| Region of Enrollment Taiwan | 1 participants |
| Region of Enrollment United States | 26 participants |
| Sex: Female, Male Female | 22 Participants |
| Sex: Female, Male Male | 26 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
Survival
Overall survival is defined as the time from birth to time of death.
Time frame: Retrospective data collected on or before the data of abstraction.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Retrospective Observational | Survival | 270.5 days |
Secondary
Invasive Ventilator-free Survival Time
Invasive ventilator-free survival is defined as the time during which the patient is alive and not invasively ventilated. For the purpose of this study, invasive ventilation is defined as mechanical ventilation via intubation of trachaeostomy.
Time frame: Retrospective data collected on or before the date of abstraction.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Retrospective Observational | Invasive Ventilator-free Survival Time | 236 days |