Hypophosphatasia is a rare inborn error of bone metabolism caused by inactivating mutations in the gene encoding the Tissue-nonspecific alkaline phosphatase isoenzyme. With deficiency of Tissue-nonspecific alkaline phosphatase, there is a buildup of extracellular inorganic pyrophosphate, which inhibits mineralization of bone matrix. MedDRA version: 20.0 Level: PT Classification code 10049933 Term: Hypophosphatasia System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Sponsors
Alexion Pharma GmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients must meet all of the following criteria for enrollment in this study: - 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-related procedures. If the minor is in a position to comprehend the nature, significance, and implications of the clinical trial and to form a rational intention in the light of these facts, then he/she must provide his/her assent prior to any study procedures being performed. - Documented diagnosis of HPP as indicated by: o Total serum alkaline phosphatase (ALP) below the lower limit of normal for age o Plasma PLP above the upper limit of normal (unless patient is receiving pyridoxine for seizures) o Radiographic evidence of HPP at screening, characterized by: * Flared and frayed metaphyses and * Severe, generalized osteopenia and * Widened growth plates and * Areas of radiolucency or sclerosis o 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 - Onset of symptoms prior to 6 months of age - Chronological age of = 5 years or adjusted age for premature infants born = 37 weeks gestation - Otherwise medically stable in the opinion of the Investigator and/or Sponsor Are the trial subjects under 18? yes Number of subjects for this age range: 100 F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Patients will be excluded from enrollment in this study if they meet any of the following exclusion criteria: - Clinically significant disease, such as, but not limited to, hepatitis C virus (HCV) / human immunodeficiency virus (HIV) / hepatitis B virus (HBV), that precludes study participation, in the opinion of the Investigator and/or Sponsor - Serum calcium or phosphate levels below the normal range - Serum 25-hydroxy (25[OH]) vitamin D below 20 ng/mL - Current evidence of treatable form of rickets - 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) - Intolerance to the study drug or any of its excipients - Previous participation in the same study - Close relation to the Investigator
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the following: • 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 • Safety and tolerability of repeated subcutaneous (SC) injections of Asfotase alfa for all treated patients;Secondary Objective: To evaluate the following: - Effect of Asfotase alfa treatment on skeletal manifestations of HPP as measured by radiographs using a Rickets Severity Scale score - For patients who are not mechanically ventilated at the time of enrollment, the percentage who are alive and ventilator-free after receiving Asfotase alfa as compared to an age-matched historical control group - Effect of Asfotase alfa treatment on respiratory function as measured by ventilator status, time on respiratory support, ventilator rate or oxygen volume, ventilator pressures, and fraction of inspired oxygen (FiO2) - 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 tooth loss for all treated patients - PK properties of Asfotase alfa - Effect of Asfotase alfa on plasma inorganic pyrophosphate (PPi) and plasma pyridoxal-5’-phosphate (PLP);Primary end point(s): • 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 • Safety and tolerability of repeated subcutaneous (SC) injections of Asfotase alfa for all treated patients;Timepoint(s) of evaluation of this end point: Efficacy endpoint: screening visit, month 3, month 6, month 9, month 12, month 18, month 24, month 30, month 36, month 42, month 48; Safety endpoint: continuous monitoring | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Effect of asfotase alfa treatment on skeletal manifestations of HPP as measured by radiographs using a Rickets Severity Scale score - For patients who are not mechanically ventilated at the time of enrollment, the percentage who are alive and ventilator-free after receiving Asfotase alfa as compared to an age-matched historical control group - 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 - 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 tooth loss for all treated patients - PK properties of Asfotase alfa - Effect of Asfotase alfa on plasma inorganic pyrophosphate (PPi) and plasma pyridoxal-5’-phosphate (PLP) - Effect of Asfotase alfa on serum parathyroid hormone (PTH);Timepoint(s) of evaluation of this end point: week-4 to day -8, day -1, day 1, day 2, day 3, week 3, week 6 day 1, week 6 day 3, month 3, month 6, month 9, month 12, month 15, month 18, month 24, month 30, month 36, month 42, month 48 Not all secondary endpoints are measured on the same day. | — |
Countries
Australia, Canada, France, Germany, Italy, Japan, Russian Federation, Saudi Arabia, Spain, Taiwan, Turkey, United Kingdom, United States
Contacts
Public ContactEuropean Clinical Trial Information
ALEXION EUROPE SAS
Outcome results
None listed