Safety and Efficacy of Asfotase Alfa in Patients With Hypophosphatasia (HPP)

Study Overview
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Brief Summary
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The aim of this study is to assess safety and efficacy of Asfotase Alfa (ALXN1215) in patients with hypophosphatasia

Official Title
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A Multicenter Study of the Safety and Efficacy of Asfotase Alfa (ALXN1215) (Human Recombinant Tissue Nonspecific Alkaline Phosphatase Fusion Protein) in Patients With Hypophosphatasia (HPP)

Conditions
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Hypophosphatasia

Intervention / Treatment
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* Drug: Asfotase Alfa (ALXN1215)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must meet one selection criteria of following 1, 2, and 3, and must meet the selection criteria of 4. Patient who has been already treated with Asfotae Alfa (ALXN1215) out of this clinical trial Patient who has been diagnosed as HPP Documented diagnosis of HPP as indicated by: Total serum alkaline phosphatase below the lower limit of normal for age 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: Generalized decreased ossification Extreme shortening of tubular bones 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: History or presence of: - Nontraumatic post-natal fracture - Delayed fracture healing Nephrocalcinosis or history of elevated serum calcium Functional craniosynostosis Respiratory compromise or rachitic chest deformity Vitamin B6 dependent seizures Failure to thrive 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: Current evidence of treatable form of rickets Serum calcium or phosphate levels below the normal range Pregnant women and nursing mothers Patient who cannot enforce suitable contraceptive measures during the clinical trial Prior treatment with bisphosphonates Treatment with an investigational drug within 1 month prior to the start of asfotase alfa treatment Current enrollment in any other study involving an investigational new drug, device or treatment for HPP (e.g., bone marrow transplantation) Clinically significant disease that precludes study participation, in the opinion of the Investigator
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Asfotase Alfa (ALXN1215)<br>Asfotase Alfa (ALXN1215) is administered 6mg/kg in total per week, divided into 3 times. | Drug: Asfotase Alfa (ALXN1215)<br> <br> * Other names: ALXN1215;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of subjects with Adverse Events as an assessment of the Safety of repeated subcutaneous (SC) injections of asfotase alfa | Safety of repeated subcutaneous (SC) injections of asfotase alfa for all treated patients | Up to 50 months or until regulatory approval | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | Overall survival is defined as the time from birth to time of death. | 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 | 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 | Up to 50 months or until regulatory approval | 
| Effect of asfotase alfa treatment on ventilator-free survival: (percentage of patients who are alive and ventilator-free after receiving asfotase alfa) | For patients who are not mechanically ventilated at the time of enrollment, the percentage who are alive and ventilator-free after receiving asfotase alfa | Up to 50 months or until regulatory approval | 
| Profile of asfotase alfa treatment on respiratory function | 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 | Up to 50 months or until regulatory approval | 
| Profile of asfotase alfa treatment on physical growth | 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 | Up to 50 months or until regulatory approval | 
| Effect of asfotase alfa treatment on development | Assessment of changes in gross motor development as measured by the developmental motor milestones for all treated patients | Up to 50 months or until regulatory approval |