Clinical trial NCT01205152: Extension Study of Protocol ENB-002-08 - Study of Asfotase Alfa in Infants and Young Children With Hypophosphatasia (HPP)
Official title: Extension Study of ENB-0040 (Human Recombinant Tissue-Nonspecific Alkaline Phosphatase Fusion Protein) in Severely Affected Infants and Young Children With Hypophosphatasia (HPP)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hypophosphatasia
Keywords: Hypophosphatasia
HPP
Bone disease
Soft bones
Low alkaline phosphatase
Genetic metabolic disorder
Alkaline phosphatase
Tissue non-specific alkaline phosphatase
Rickets
Osteomalacia
Lead sponsor: Alexion Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2010-09-20
Enrollment: 10
Sex: ALL
Minimum age (years): 24
Maximum age (years): 42
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This clinical trial studied the long term safety and efficacy of asfotase alfa in infants and young children with infantile onset HPP who completed study ENB-002-08 (NCT00744042).

Partial funding for this study was provided by the Office of Orphan Product Development (OOPD).

Detailed description: Asfotase Alfa was formerly referred to as ENB-0040

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 limited data available on the natural course of this disease over time, particularly in patients with the juvenile-onset form.

Eligibility criteria: Inclusion Criteria

* Patient completed participation in ENB-002-08 (NCT00744042)
* Written informed consent by parent or other legal guardian prior to any study procedures being performed
* Parent or other legal guardian willing to comply with study requirements

Exclusion Criteria

* History of sensitivity to any of the constituents of the study drug
* Clinically significant disease that precludes study participation
* Enrollment in any study (other than ENB-002-08) involving an investigational drug, device, or treatment for HPP (e.g., bone marrow transplantation)

Primary outcomes:
measure: Long-term Tolerability of Subcutaneous (SC) Asfotase Alfa
timeFrame: 84 months
measure: Long-term Efficacy of Asfotase Alfa in Treating Rickets in Infants and Young Children With Hypophosphatasia (HPP).
timeFrame: Up to 90 Months
Secondary outcomes:
measure: Long-term Pharmacodynamics (PD) of SC Asfotase Alfa: Plasma Inorganic Pyrophosphate (PPi) Levels
timeFrame: Up to 90 Months
measure: Long-term Pharmacodynamics (PD) of SC Asfotase Alfa: Pyridoxal-5-phosphate (PLP) Levels
timeFrame: Up to 90 Months
measure: Effect of SC Asfotase Alfa on Growth: Weight Z-scores
timeFrame: Up to 90 Months
measure: Effect of SC Asfotase Alfa on Growth: Height/Length Z-scores
timeFrame: Up to 90 Months
measure: Effect of SC Asfotase Alfa on Respiratory Function
timeFrame: Up to 90 Months
Other outcomes:
Locations:
city: Wilmington
country: United States
facility: Alfred I. DuPont Hospital for Children
state: Delaware
city: Springfield
country: United States
facility: St. John's Medical Research Institute
state: Missouri
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Green Bay
country: United States
facility: St. Vincent Hospital
state: Wisconsin
city: Al Ain
country: United Arab Emirates
facility: Tawam Hospital
state: Abu-Dhabi
city: Belfast
country: United Kingdom
facility: Royal Maternity Hospital, Royal Belfast Hospital for Sick Children
state: Northern Ireland
city: Sheffield
country: United Kingdom
facility: Sheffield Children's Hospital
Study officials:
References:
citation: 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.
citation: Whyte MP, Simmons JH, Moseley S, Fujita KP, Bishop N, Salman NJ, Taylor J, Phillips D, McGinn M, McAlister WH. Asfotase alfa for infants and young children with hypophosphatasia: 7 year outcomes of a single-arm, open-label, phase 2 extension trial. Lancet Diabetes Endocrinol. 2019 Feb;7(2):93-105. doi: 10.1016/S2213-8587(18)30307-3. Epub 2018 Dec 14.
citation: 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.