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

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)

This clinical trial studies the safety and efficacy of asfotase alfa in infants and young children with infantile onset HPP.

Hypophosphatasia (HPP) is a life-threatening, genetic, and ultra-rare metabolic disease characterized by defective bone mineralization and impaired phosphate and calcium regulation that can lead to progressive damage to multiple vital organs, including destruction and deformity of bones, profound muscle weakness, seizures, impaired renal function, and respiratory failure. There are no approved disease-modifying treatments for patients with this disease. There is also limited data available on the natural course of this disease over time, particularly in patients with the juvenile-onset form.

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