Hypophosphatasia
Conditions
Brief summary
The aim of this study is to assess safety and efficacy of Asfotase Alfa (ALXN1215) in patients with hypophosphatasia
Interventions
DRUGAsfotase Alfa (ALXN1215)
Sponsors
Osaka University Graduate School of Medicine
Translational Research Center for Medical Innovation, Kobe, Hyogo, Japan
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
Patients must meet one selection criteria of following 1, 2, and 3, and must meet the selection criteria of 4. 1. Patient who has been already treated with Asfotae Alfa (ALXN1215) out of this clinical trial 2. Patient who has been diagnosed as HPP 3. Documented diagnosis of HPP as indicated by: <!-- --> 1. Total serum alkaline phosphatase below the lower limit of normal for age 2. Ultrasonographic features of prenatal, characterized by: 1\) severe short extremities (femur length \<-4SD in second and third trimesters) 2) extending into the metaphysis (femur metaphysis length or femur length \>0.33) 3) craniotabes 4) Hypoplastic thorax (Thoracic or abdominal circumference \<0.6) (3) Computed tomographic findings of prenatal, characterized by: 1. Generalized decreased ossification 2. Extreme shortening of tubular bones 3. Hypoplastic thorax (4) Radiographic evidence of HPP, characterized by: 1\) Flared and frayed metaphyses 2) Severe, generalized osteopenia 3) Widened growth plates 4) Areas of radiolucency or sclerosis (5) Two or more of the following HPP-related findings: 1. History or presence of: \- Nontraumatic post-natal fracture \- Delayed fracture healing 2. Nephrocalcinosis or history of elevated serum calcium 3. Functional craniosynostosis 4. Respiratory compromise or rachitic chest deformity 5. Vitamin B6 dependent seizures 6. Failure to thrive 7. Premature tooth loss (6) Patient who have the mutation of tissue non-specific ALP gene 4. Parent or legal guardian(s) must provide written informed consent prior to any study procedures being performed and must be willing to comply with all study-required procedures
Exclusion criteria
1. Current evidence of treatable form of rickets 2. Serum calcium or phosphate levels below the normal range 3. Pregnant women and nursing mothers 4. Patient who cannot enforce suitable contraceptive measures during the clinical trial 5. Prior treatment with bisphosphonates 6. Treatment with an investigational drug within 1 month prior to the start of asfotase alfa treatment 7. Current enrollment in any other study involving an investigational new drug, device or treatment for HPP (e.g., bone marrow transplantation) 8. Clinically significant disease that precludes study participation, in the opinion of the Investigator
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of subjects with Adverse Events as an assessment of the Safety of repeated subcutaneous (SC) injections of asfotase alfa | Up to 50 months or until regulatory approval | Safety of repeated subcutaneous (SC) injections of asfotase alfa for all treated patients |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Effect of asfotase alfa treatment on skeletal manifestations of HPP as measured by radiographs using a qualitative Radiographic Global Impression of Change (RGI-C) scale | Up to 50 months or until regulatory approval | Effect of asfotase alfa treatment on skeletal manifestations of HPP as measured by radiographs using a qualitative Radiographic Global Impression of Change (RGI-C) scale for all treated patients |
| Effect of asfotase alfa treatment on ventilator-free survival: (percentage of patients who are alive and ventilator-free after receiving asfotase alfa) | Up to 50 months or until regulatory approval | For patients who are not mechanically ventilated at the time of enrollment, the percentage who are alive and ventilator-free after receiving asfotase alfa |
| Overall survival | Up to 50 months or until regulatory approval | Overall survival is defined as the time from birth to time of death. |
| Profile of asfotase alfa treatment on physical growth | Up to 50 months or until regulatory approval | Effect of asfotase alfa treatment on physical growth as measured by body weight, length, arm span, head circumference, and chest circumference for all treated patients |
| Effect of asfotase alfa treatment on development | Up to 50 months or until regulatory approval | Assessment of changes in gross motor development as measured by the developmental motor milestones for all treated patients |
| Profile of asfotase alfa treatment on respiratory function | Up to 50 months or until regulatory approval | Effect of asfotase alfa treatment on respiratory function as measured by ventilator status, time on respiratory support (including time on ventilator or supplemental oxygen), ventilator rate or oxygen volume, ventilator pressures, and fraction of inspired oxygen (FiO2) for all treated patients |
Countries
Japan
Outcome results
None listed