Safety and Efficacy Study of Asfotase Alfa in Severely Affected Infants With Hypophosphatasia (HPP)

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT00744042
• Date of registration: 27/08/2008
• Prospective Registration: Yes
• Primary sponsor: Alexion Pharmaceuticals
• Public title: Safety and Efficacy Study of Asfotase Alfa in Severely Affected Infants With Hypophosphatasia (HPP)
• Scientific title: A Multicenter, Open-Label Study of the Safety, Tolerability and Pharmacology of Asfotase Alfa in up to 10 Severely Affected Patients With for the Treatment of Severely Affected Patients With Infantile Hypophosphatasia (HPP)
• Date of first enrolment: September 2008
• Target sample size: 11
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT00744042
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1/Phase 2

Countries of recruitment

Canada, United Arab Emirates, United Kingdom, United States

Key inclusion & exclusion criteria

Inclusion Criteria:

- Legal guardian(s) must provide informed consent prior to any study procedures

- Documented diagnosis of severe HPP as indicated by:

- Total serum alkaline phosphatase at least 3 standard deviations (SD) below the
mean for age

- Plasma pyridoxal 5'-phosphate (PLP) at least 4 times the upper limit of normal

- Radiographic evidence of HPP (hypophosphatasia), characterized by:

- Flared and frayed metaphyses

- Severe, generalized osteopenia

- Widened growth plates

- One or more HPP-related findings:

- History or presence of:

- Non-traumatic post-natal fracture

- Delayed fracture healing

- History of elevated serum calcium

- Functional craniosynostosis with decreased head circumference growth

- Nephrocalcinosis

- Respiratory compromise

- Rachitic chest deformity and/or vitamin B6 dependent seizures

- Failure to thrive

- Onset of symptoms prior to 6 months of age

- Age = 36 months

- Otherwise medically stable (patient may be on ventilatory support)

- Legal guardian(s) must be willing to comply with the study

Exclusion Criteria:

- History of sensitivity to any of the constituents of the study drug

- Current or prior clinically significant cardiovascular, endocrinologic, hematologic,
hepatic, immunologic, metabolic, infectious, urologic, pulmonary, neurologic,
dermatologic, renal condition and/or other major disease which, in the opinion of the
investigator, precludes study participation

- Treatment with an investigational drug within 1 month prior to the start of study drug
administration

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

- Low serum calcium, phosphate or 25(OH) vitamin D

- Current evidence of a treatable form of rickets

- Prior treatment with bisphosphonate



Age minimum: N/A
Age maximum: 36 Months
Gender: All

Health Condition(s) or Problem(s) studied

Hypophosphatasia (HPP)

Intervention(s)

Biological: asfotase alfa

Primary Outcome(s)

Change in Rickets Severity From Baseline to Week 24, Based on Assessment of Skeletal Radiographs Using Radiologic Global Impression of Change (RGI-C) [Time Frame: 24 weeks]

Secondary Outcome(s)

Area Under Serum Concentration-time Curve to Last Measurable Concentration of Asfotase Alfa (AUCt) [Time Frame: Study Week 1 (0 to 168 hours post-dose). Study Week 2 and Study Week 3 (0 to 48 hours post-dose).]

Maximum Serum Concentration of Asfotase Alfa (Cmax) [Time Frame: Study Week 1 (0 to 168 hours post-dose). Study Week 2 and Study Week 3 (0 to 48 hours post-dose)]

Time at Maximum Serum Concentration of Asfotase Alfa (Tmax) [Time Frame: Study Week 1 (0 to 168 hours post-dose). Study Week 2 and Study Week 3 (0 to 48 hours post-dose).]

Secondary ID(s)

ENB-002-08

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 30/09/2011
• URL: https://clinicaltrials.gov/ct2/show/results/NCT00744042