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

NCT ID: NCT00744042

Last Updated: 2019-04-01

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

11 participants

Study Classification

INTERVENTIONAL

Study Start Date

2008-09-30

Study Completion Date

2010-05-31

Brief Summary

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

Detailed Description

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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.

Conditions

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Hypophosphatasia (HPP)

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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asfotase alfa

asfotase alfa

Group Type OTHER

asfotase alfa

Intervention Type BIOLOGICAL

Interventions

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asfotase alfa

Intervention Type BIOLOGICAL

Other Intervention Names

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Asfotase Alfa was formerly referred to as ENB-0040 Human Recombinant Tissue Nonspecific Alkaline Phosphatase Fusion Protein

Eligibility Criteria

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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
Maximum Eligible Age

36 Months

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Alexion Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Arkansas Children's Hospital

Little Rock, Arkansas, United States

Site Status

Alfred I. duPont Hospital for Children

Wilmington, Delaware, United States

Site Status

St. John's Hospital

Springfield, Missouri, United States

Site Status

University of Nebraska Medical Center, Munroe-Meyer Institute

Omaha, Nebraska, United States

Site Status

Vanderbilt Children's Hospital

Nashville, Tennessee, United States

Site Status

St. Vincent Hospital

Green Bay, Wisconsin, United States

Site Status

The University of Manitoba Health Sciences Centre

Winnipeg, Manitoba, Canada

Site Status

Tawam-John Hopkins Hospital

Al Ain City, Abu Dhabi Emirate, United Arab Emirates

Site Status

Sheffield Children's Hospital

Sheffield, England, United Kingdom

Site Status

Royal Belfast Hospital for Sick Children

Belfast, Northern Ireland, United Kingdom

Site Status

Countries

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United States Canada United Arab Emirates United Kingdom

References

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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.

Reference Type BACKGROUND
PMID: 18086009 (View on PubMed)

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. No abstract available.

Reference Type BACKGROUND
PMID: 18318644 (View on PubMed)

Padidela 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.

Reference Type DERIVED
PMID: 32762706 (View on PubMed)

Whyte 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.

Reference Type DERIVED
PMID: 26529632 (View on PubMed)

Whyte 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.

Reference Type DERIVED
PMID: 22397652 (View on PubMed)

Related Links

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http://www.hypophosphatasia.com

Hypophosphatasia Website

http://www.hypophosphatasia.com/hcp/

Hypophosphatasia Website for Healthcare Providers

http://www.softbones.org

US Hypophosphatasia Group (Soft Bones)

Other Identifiers

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ENB-002-08

Identifier Type: -

Identifier Source: org_study_id

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