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

Hypophosphatasia Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT02456038
• Other study ID #: HPPJEAP-01
• Secondary ID: UMIN000014816
• Status: Enrolling by invitation
• Phase: Phase 2
• First received: March 26, 2015
• Last updated: June 2, 2015
• Start date: August 2014

Study information

• Verified date: June 2015
• Source: Translational Research Informatics Center, Kobe, Hyogo, Japan
• Contact: n/a
• Is FDA regulated: No
• Health authority: Japan: Ministry of Health, Labor and Welfare
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 20
• Est. primary completion date: March 2017
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A and older

Eligibility

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hypophosphatasia

Intervention

Drug:
• Asfotase Alfa (ALXN1215)

Locations

Country	Name	City	State
Japan	Nippon Medical School Hospital	Bunkyo-ku	Tokyo
Japan	National Hospital Organization Nagara Medical Center	Gifu-city	Gifu-prefecture
Japan	Hamamatsu University Hospital	Hamamatsu-city	Shizuoka-prefecture
Japan	Hiroshima University Hospital	Hiroshima-city	Hiroshima-prefecture
Japan	Osaka Medical Center and Research Institute for Maternal and Child Health	Izumi-city	Osaka-prefecture
Japan	Showa General Hospital	Kodaira-city	Tokyo
Japan	Kurume University Hospital	Kurume-city	Fukuoka-prefecture
Japan	Niigata University Medical & Dental Hospital	Niigata-city	Niigata-prefecture
Japan	Saitama Children's Medical Center	Saitama-city	Saitama-prefecture
Japan	Hokkaido University Hospital	Sapporo-city	Hokkaido-prefecture
Japan	Tohoku University Hospital	Sendai-city	Miyagi-prefecture
Japan	Osaka University Hospital	Suita-city	Osaka-prefecture

Sponsors (2)

Lead Sponsor	Collaborator
Translational Research Informatics Center, Kobe, Hyogo, Japan	Osaka University Graduate School of Medicine

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Secondary	Overall survival	Overall survival is defined as the time from birth to time of death.	Up to 50 months or until regulatory approval	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No