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)
1 other identifier
interventional
11
4 countries
10
Brief Summary
This clinical trial studies the safety and efficacy of asfotase alfa in infants and young children with infantile onset HPP.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_1
Started Sep 2008
10 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 27, 2008
CompletedFirst Posted
Study publicly available on registry
August 29, 2008
CompletedStudy Start
First participant enrolled
September 1, 2008
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 1, 2010
CompletedStudy Completion
Last participant's last visit for all outcomes
May 1, 2010
CompletedResults Posted
Study results publicly available
September 30, 2011
CompletedApril 1, 2019
March 1, 2019
1.7 years
August 27, 2008
May 15, 2011
March 28, 2019
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
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 Outcomes (3)
Maximum Serum Concentration of Asfotase Alfa (Cmax)
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)
Study Week 1 (0 to 168 hours post-dose). Study Week 2 and Study Week 3 (0 to 48 hours post-dose).
Area Under Serum Concentration-time Curve to Last Measurable Concentration of Asfotase Alfa (AUCt)
Study Week 1 (0 to 168 hours post-dose). Study Week 2 and Study Week 3 (0 to 48 hours post-dose).
Study Arms (1)
asfotase alfa
OTHERasfotase alfa
Interventions
Eligibility Criteria
You may qualify if:
- 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
- +7 more criteria
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (10)
Arkansas Children's Hospital
Little Rock, Arkansas, 72202, United States
Alfred I. duPont Hospital for Children
Wilmington, Delaware, 19803, United States
St. John's Hospital
Springfield, Missouri, 65804, United States
University of Nebraska Medical Center, Munroe-Meyer Institute
Omaha, Nebraska, 68114, United States
Vanderbilt Children's Hospital
Nashville, Tennessee, 37232, United States
St. Vincent Hospital
Green Bay, Wisconsin, 54301, United States
The University of Manitoba Health Sciences Centre
Winnipeg, Manitoba, R3A 1S1, Canada
Tawam-John Hopkins Hospital
Al Ain City, Abu Dhabi Emirate, United Arab Emirates
Sheffield Children's Hospital
Sheffield, England, S10 2TH, United Kingdom
Royal Belfast Hospital for Sick Children
Belfast, Northern Ireland, United Kingdom
Related Publications (5)
Millan 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. doi: 10.1359/jbmr.071213.
PMID: 18086009BACKGROUNDDrake MT, Khosla S. Bone-targeted replacement therapy for hypophosphatasia. J Bone Miner Res. 2008 Jun;23(6):775-6. doi: 10.1359/jbmr.080305. No abstract available.
PMID: 18318644BACKGROUNDPadidela R, Yates R, Benscoter D, McPhail G, Chan E, Nichani J, Mughal MZ, Myer C 4th, Narayan O, Nissenbaum C, Wilkinson S, Zhou S, Saal HM. Characterization of tracheobronchomalacia in infants with hypophosphatasia. Orphanet J Rare Dis. 2020 Aug 6;15(1):204. doi: 10.1186/s13023-020-01483-9.
PMID: 32762706DERIVEDWhyte MP, Rockman-Greenberg C, Ozono K, Riese R, Moseley S, Melian A, Thompson DD, Bishop N, Hofmann C. Asfotase Alfa Treatment Improves Survival for Perinatal and Infantile Hypophosphatasia. J Clin Endocrinol Metab. 2016 Jan;101(1):334-42. doi: 10.1210/jc.2015-3462. Epub 2015 Nov 3.
PMID: 26529632DERIVEDWhyte MP, Greenberg CR, Salman NJ, Bober MB, McAlister WH, Wenkert D, Van Sickle BJ, Simmons JH, Edgar TS, Bauer ML, Hamdan MA, Bishop N, Lutz RE, McGinn M, Craig S, Moore JN, Taylor JW, Cleveland RH, Cranley WR, Lim R, Thacher TD, Mayhew JE, Downs M, Millan JL, Skrinar AM, Crine P, Landy H. Enzyme-replacement therapy in life-threatening hypophosphatasia. N Engl J Med. 2012 Mar 8;366(10):904-13. doi: 10.1056/NEJMoa1106173.
PMID: 22397652DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Alexion Pharma GmbH
- Organization
- Alexion Pharma GmbH
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- LTE60
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 27, 2008
First Posted
August 29, 2008
Study Start
September 1, 2008
Primary Completion
May 1, 2010
Study Completion
May 1, 2010
Last Updated
April 1, 2019
Results First Posted
September 30, 2011
Record last verified: 2019-03