Open-Label Study of Asfotase Alfa in Infants and Children = 5 Years of Age With Hypophosphatasia (HPP)

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT01176266
• Date of registration: 29/07/2010
• Prospective Registration: No
• Primary sponsor: Alexion Pharmaceuticals
• Public title: Open-Label Study of Asfotase Alfa 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: July 2010
• Target sample size: 69
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT01176266
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2/Phase 3

Countries of recruitment

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

Key inclusion & exclusion criteria

Inclusion Criteria:

Patients must meet all of the following criteria for enrollment in this study:

1. 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. Where appropriate and required by local regulations, patient assent should
also be provided prior to any study procedures being performed.

2. Documented diagnosis of HPP as indicated by:

1. Total serum alkaline phosphatase (ALP) below the lower limit of normal for age
NOTE: Historical values for ALP may be used to determine patient eligibility.

2. Plasma pyridoxal-5'-phosphate (PLP) above the upper limit of normal (unless
patient is receiving pyridoxine for seizures) NOTE: Historical values for PLP may
be used to determine patient eligibility.

3. 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

4. Two or more of the following HPP-related findings:

- History or presence of: i) Nontraumatic post-natal fracture or ii) Delayed
fracture healing

- Nephrocalcinosis or history of elevated serum calcium

- Functional craniosynostosis

- Respiratory compromise or rachitic chest deformity

- Vitamin B6-responsive seizures

- Failure to thrive

3. Onset of symptoms prior to 6 months of age

4. Chronological age or adjusted age for premature infants born = 37 weeks gestation of =
5 years

5. Otherwise medically stable in the opinion of the Investigator and/or Sponsor

Exclusion criteria:

Patients will be excluded from enrollment in this study if they meet any of the following
exclusion criteria:

1. Clinically significant disease that precludes study participation, in the opinion of
the Investigator and/or Sponsor

2. Serum calcium or phosphate levels below the normal range

3. Current evidence of treatable form of rickets

4. Prior treatment with bisphosphonates

5. Treatment with an investigational drug within 1 month prior to the start of asfotase
alfa treatment

6. Current enrollment in any other study involving an investigational new drug, device or
treatment for HPP (e.g., bone marrow transplantation)

7. Intolerance to the investigational product (IP) or any of its excipients

8. Previous participation in the same study

9. Family relative of the Investigator



Age minimum: N/A
Age maximum: 5 Years
Gender: All

Health Condition(s) or Problem(s) studied

Hypophosphatasia

Intervention(s)

Drug: asfotase alfa

Primary Outcome(s)

Effect of Asfotase Alfa Treatment on Skeletal Manifestations of Hypophosphatasia (HPP) [Time Frame: From Baseline to Week 24]

Safety and Tolerability of Repeated Subcutaneous (SC) Injections of Asfotase Alfa [Time Frame: Up to 72 months or until regulatory approval in the country of residence. Patients received study drug for a median duration of 829.0 days, with a range from 6 to 2116 days (ie, from 0.9 week to 5.8 years).]

Secondary Outcome(s)

Effect of Asfotase Alfa Treatment on Physical Growth - Weight Z-scores Change From Baseline to Last Obtained Value [Time Frame: Up to 72 months or until regulatory approval in the country of residence. Patients received study drug for a median duration of 829.0 days, with a range from 6 to 2116 days (ie, from 0.9 week to 5.8 years).]

Pharmacokinetic (PK) Properties of Asfotase Alfa (Cmax) [Time Frame: PK parameters were calculated using Week 6 study visit data. Week 6 study visit blood samples for PK testing were drawn pre-dose and 6, 12, 24, 32, and 48 hours post dose]

Effect of Asfotase Alfa on Biomarkers - Plasma Pyridoxal-5' Phosphate (PLP) Change From Baseline to Last Obtained Value [Time Frame: Up to 72 months or until regulatory approval in the country of residence. Patients received study drug for a median duration of 829.0 days, with a range from 6 to 2116 days (ie, from 0.9 week to 5.8 years).]

Effect of Asfotase Alfa Treatment on Skeletal Manifestations of Hypophosphatasia (HPP) [Time Frame: Up to 72 Months or regulatory approval in the country of residence. Patients received study drug for a median duration of 829.0 days, with a range from 6 to 2116 days (ie, from 0.9 week to 5.8 years).]

Effect of Asfotase Alfa Treatment on Ventilator-free Survival (Week 312) [Time Frame: Up to 72 months or until regulatory approval in the country of residence. Patients received study drug for a median duration of 829.0 days, with a range from 6 to 2116 days (ie, from 0.9 week to 5.8 years).]

Pharmacokinetic (PK) Properties of Asfotase Alfa (Tlast) [Time Frame: PK parameters were calculated using Week 6 study visit data. Week 6 study visit blood samples for PK testing were drawn pre-dose and 6, 12, 24, 32, and 48 hours post dose]

Pharmacokinetic (PK) Properties of Asfotase Alfa (AUCt) [Time Frame: PK parameters were calculated using Week 6 study visit data. Week 6 study visit blood samples for PK testing were drawn pre-dose and 6, 12, 24, 32, and 48 hours post dose]

Effect of Asfotase Alfa on Biomarkers - Plasma Inorganic Pyrophosphate (PPi) Change From Baseline to Last Obtained Value [Time Frame: Up to 72 months or until regulatory approval in the country of residence. Patients received study drug for a median duration of 829.0 days, with a range from 6 to 2116 days (ie, from 0.9 week to 5.8 years).]

Effect of Asfotase Alfa on Serum Parathyroid Hormone (PTH) - Change From Baseline to Last Obtained Value [Time Frame: Up to 72 months or until regulatory approval in the country of residence. Patients received study drug for a median duration of 829.0 days, with a range from 6 to 2116 days (ie, from 0.9 week to 5.8 years).]

Effect of Asfotase Alfa Treatment on Physical Growth - Length/Height Z-scores Change From Baseline to Last Obtained Value [Time Frame: Up to 72 months or until regulatory approval in the country of residence. Patients received study drug for a median duration of 829.0 days, with a range from 6 to 2116 days (ie, from 0.9 week to 5.8 years).]

Effect of Asfotase Alfa Treatment on Respiratory Function [Time Frame: Up to 72 months or until regulatory approval in the country of residence. Patients received study drug for a median duration of 829.0 days, with a range from 6 to 2116 days (ie, from 0.9 week to 5.8 years).]

Effect of Asfotase Alfa Treatment on Tooth Loss [Time Frame: Up to 72 months or until regulatory approval in the country of residence. Patients received study drug for a median duration of 829.0 days, with a range from 6 to 2116 days (ie, from 0.9 week to 5.8 years).]

Pharmacokinetic (PK) Properties of Asfotase Alfa (Tmax) [Time Frame: PK parameters were calculated using Week 6 study visit data. Week 6 study visit blood samples for PK testing were drawn pre-dose and 6, 12, 24, 32, and 48 hours post dose]

Secondary ID(s)

ENB-010-10

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 26/02/2018
• URL: https://clinicaltrials.gov/ct2/show/results/NCT01176266