Clinical trial NCT02456038: Safety and Efficacy of Asfotase Alfa in Patients With Hypophosphatasia (HPP)
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hypophosphatasia
Lead sponsor: Translational Research Center for Medical Innovation, Kobe, Hyogo, Japan
Sponsor class: OTHER
Collaborators: name: Osaka University Graduate School of Medicine
First posted: 2015-05-28
Enrollment: 13
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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


Eligibility criteria: 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:

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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

Primary outcomes:
measure: Number of subjects with Adverse Events as an assessment of the Safety of repeated subcutaneous (SC) injections of asfotase alfa
timeFrame: Up to 50 months or until regulatory approval
Secondary outcomes:
measure: Overall survival
timeFrame: Up to 50 months or until regulatory approval
measure: 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
timeFrame: Up to 50 months or until regulatory approval
measure: Effect of asfotase alfa treatment on ventilator-free survival: (percentage of patients who are alive and ventilator-free after receiving asfotase alfa)
timeFrame: Up to 50 months or until regulatory approval
measure: Profile of asfotase alfa treatment on respiratory function
timeFrame: Up to 50 months or until regulatory approval
measure: Profile of asfotase alfa treatment on physical growth
timeFrame: Up to 50 months or until regulatory approval
measure: Effect of asfotase alfa treatment on development
timeFrame: Up to 50 months or until regulatory approval
Other outcomes:
Locations:
city: Kurume-city
country: Japan
facility: Kurume University Hospital
state: Fukuoka-prefecture
city: Gifu-city
country: Japan
facility: National Hospital Organization Nagara Medical Center
state: Gifu-prefecture
city: Hiroshima-city
country: Japan
facility: Hiroshima University Hospital
state: Hiroshima-prefecture
city: Sapporo-city
country: Japan
facility: Hokkaido University Hospital
state: Hokkaido-prefecture
city: Sendai-city
country: Japan
facility: Tohoku University Hospital
state: Miyagi-prefecture
city: Niigata-city
country: Japan
facility: Niigata University Medical & Dental Hospital
state: Niigata-prefecture
city: Izumi-city
country: Japan
facility: Osaka Medical Center and Research Institute for Maternal and Child Health
state: Osaka-prefecture
city: Suita-city
country: Japan
facility: Osaka University Hospital
state: Osaka-prefecture
city: Saitama-city
country: Japan
facility: Saitama Children's Medical Center
state: Saitama-prefecture
city: Hamamatsu-city
country: Japan
facility: Hamamatsu University Hospital
state: Shizuoka-prefecture
city: Bunkyo-ku
country: Japan
facility: Nippon Medical School Hospital
state: Tokyo
city: Kodaira-city
country: Japan
facility: Showa General Hospital
state: Tokyo
Study officials:
affiliation: Osaka University Hospital
name: Keiichi Ozono
role: PRINCIPAL_INVESTIGATOR
References: