An Open-Label, Multicenter, Multinational Study of the Safety, Efficacy and Pharmacokinetics of Asfotase alfa (human recombinant tissue nonspecific alkaline phosphatase fusion protein) in Infants and Children =5 Years of Age with Hypophosphatasia (HPP)

• Register: EUCTR
• Last refreshed on: 29 May 2017
• Main ID: EUCTR2010-019850-42-DE
• Date of registration: 15/10/2010
• Prospective Registration: Yes
• Primary sponsor: Alexion Pharma GmbH
• Public title: An Open-Label, Multicenter, Multinational Study of the Safety, Efficacy and Pharmacokinetics of Asfotase alfa (human recombinant tissue nonspecific alkaline phosphatase fusion protein) in Infants and Children =5 Years of Age with Hypophosphatasia (HPP)
• Scientific title: An Open-Label, Multicenter, Multinational Study of the Safety, Efficacy and Pharmacokinetics of Asfotase alfa (human recombinant tissue nonspecific alkaline phosphatase fusion protein) in Infants and Children =5 Years of Age with Hypophosphatasia (HPP)
• Date of first enrolment: 04/03/2011
• Target sample size: 100
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-019850-42
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: Placebo: Other:
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Canada, France, Germany, Italy, Japan, Russian Federation, Saudi Arabia, Spain, Taiwan, Turkey, United Kingdom, United States

Contacts

• Name: European Clinical Trial Information
• Affiliation: ALEXION EUROPE SAS

• Name: European Clinical Trial Information
• Affiliation: ALEXION EUROPE SAS

Key inclusion & exclusion 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:
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


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

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

Therapeutic area: Body processes [G] - Genetic Phenomena [G05]

Intervention(s)

Trade Name: Strensiq
Product Name: Asfotase alfa
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Asfotase alfa
Other descriptive name: Human Recombinant Tissue Non-Specific Alkaline Phosphatase Fusion Protein
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 40-

Trade Name: Strensiq
Product Name: Asfotase alfa
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Asfotase alfa
Other descriptive name: Human Recombinant Tissue Non-Specific Alkaline Phosphatase Fusion Protein
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 100-

Primary Outcome(s)

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

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 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

Secondary Outcome(s)

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.

Secondary ID(s)

ENB-010-10

Source(s) of Monetary Support

Alexion Pharma GmbH