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

Hypophosphatasia (HPP) Clinical Trial

Official 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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00744042
• Other study ID #: ENB-002-08
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: September 2008
• Est. completion date: May 2010

Study information

• Verified date: March 2019
• Source: Alexion Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 11
• Est. completion date: May 2010
• Est. primary completion date: May 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 36 Months

Eligibility

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

Related Conditions & MeSH terms

• Hypophosphatasia
• Hypophosphatasia (HPP)

Intervention

Biological:
• asfotase alfa

Locations

Country	Name	City	State
Canada	The University of Manitoba Health Sciences Centre	Winnipeg	Manitoba
United Arab Emirates	Tawam-John Hopkins Hospital	Al Ain	Abu-Dhabi
United Kingdom	Royal Belfast Hospital for Sick Children	Belfast	Northern Ireland
United Kingdom	Sheffield Children's Hospital	Sheffield	England
United States	St. Vincent Hospital	Green Bay	Wisconsin
United States	Arkansas Children's Hospital	Little Rock	Arkansas
United States	Vanderbilt Children's Hospital	Nashville	Tennessee
United States	University of Nebraska Medical Center, Munroe-Meyer Institute	Omaha	Nebraska
United States	St. John's Hospital	Springfield	Missouri
United States	Alfred I. duPont Hospital for Children	Wilmington	Delaware

Sponsors (1)

Lead Sponsor	Collaborator
Alexion Pharmaceuticals

Countries where clinical trial is conducted

United States,  Canada,  United Arab Emirates,  United Kingdom, 

References & Publications (2)

Drake MT, Khosla S. Bone-targeted replacement therapy for hypophosphatasia. J Bone Miner Res. 2008 Jun;23(6):775-6. doi: 10.1359/jbmr.080305. — View Citation

Millán JL, Narisawa S, Lemire I, Loisel TP, Boileau G, Leonard P, Gramatikova S, Terkeltaub R, Camacho NP, McKee MD, Crine P, Whyte MP. Enzyme replacement therapy for murine hypophosphatasia. J Bone Miner Res. 2008 Jun;23(6):777-87. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Rickets Severity From Baseline to Week 24, Based on Assessment of Skeletal Radiographs Using Radiologic Global Impression of Change (RGI-C)	A 7-point RGI-C (Radiographic Global Impression of Change) score was used to rate change in rickets severity. Scores ranged from -3 (severe worsening of rickets) to +3 (complete healing of rickets). Only those patients with a minimum score of +2 indicating substantial healing of rickets) were considered "responders". Three pediatric radiologists not affiliated with the conduct of the study performed the ratings. Average scores were derived for each patient at each assessment.	24 weeks
Secondary	Maximum Serum Concentration of Asfotase Alfa (Cmax)	Maximum serum concentration observed during intensive PK sampling interval.	Study Week 1 (0 to 168 hours post-dose). Study Week 2 and Study Week 3 (0 to 48 hours post-dose)
Secondary	Time at Maximum Serum Concentration of Asfotase Alfa (Tmax)	Time at maximum serum concentration observed during intensive PK sampling interval.	Study Week 1 (0 to 168 hours post-dose). Study Week 2 and Study Week 3 (0 to 48 hours post-dose).
Secondary	Area Under Serum Concentration-time Curve to Last Measurable Concentration of Asfotase Alfa (AUCt)	Area under serum concentration-time curve to last measurable concentration during intensive PK sampling interval.	Study Week 1 (0 to 168 hours post-dose). Study Week 2 and Study Week 3 (0 to 48 hours post-dose).

External Links

•   HPP support group
•   Hypophosphatasia Website
•   Hypophosphatasia Website for Healthcare Providers
•   Hypophosphatasie Europe
•   US Hypophosphatasia Group (Soft Bones)
•   Yahoo health group for HPP with an international list serve where patients can correspond and post questions to the group