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

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)

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

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