NCT01205152

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).

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
10

participants targeted

Target at below P25 for phase_2

Timeline
Completed

Started Apr 2009

Longer than P75 for phase_2

Geographic Reach
3 countries

8 active sites

Status
completed

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

Study Start

First participant enrolled

April 1, 2009

Completed
1.5 years until next milestone

First Submitted

Initial submission to the registry

September 17, 2010

Completed
3 days until next milestone

First Posted

Study publicly available on registry

September 20, 2010

Completed
5.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 1, 2016

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

August 1, 2016

Completed
1.3 years until next milestone

Results Posted

Study results publicly available

November 17, 2017

Completed
Last Updated

March 13, 2019

Status Verified

March 1, 2019

Enrollment Period

7.3 years

First QC Date

September 17, 2010

Results QC Date

August 14, 2017

Last Update Submit

March 11, 2019

Conditions

Hypophosphatasia

Keywords

HypophosphatasiaHPPBone diseaseSoft bonesLow alkaline phosphataseGenetic metabolic disorderAlkaline phosphataseTissue non-specific alkaline phosphataseRicketsOsteomalacia

Outcome Measures

Primary Outcomes (2)

  • Long-term Tolerability of Subcutaneous (SC) Asfotase Alfa

    Outcome measure is the number of patients with 1 or more treatment-emergent adverse event. The time period is from Baseline in the ENB-003-08 study to the end of the ENB-003-08 study.

    84 months

  • Long-term Efficacy of Asfotase Alfa in Treating Rickets in Infants and Young Children With Hypophosphatasia (HPP).

    Outcome measure is the evaluation of radiographic change in rickets severity using a qualitative Radiographic Global Impression of Change (RGI-C) Scale. Skeletal radiographs obtained at the patient's last assessment were compared with skeletal radiographs obtained before initiation of treatment (Baseline in Study ENB-002-08 \[NCT00744042\]). The RGI-C is a 7-point rating scale that ranges from -3 (indicative of severe worsening of HPP-associated rickets) to +3 (indicative of complete or near complete healing of HPP-associated rickets). The time period is pre-dose (Baseline from ENB-002-08 study) to the last assessment for each patient in the ENB-003-08 study, which represents up to 90 months of exposure for the combined studies.

    Up to 90 Months

Secondary Outcomes (5)

  • Long-term Pharmacodynamics (PD) of SC Asfotase Alfa: Plasma Inorganic Pyrophosphate (PPi) Levels

    Up to 90 Months

  • Long-term Pharmacodynamics (PD) of SC Asfotase Alfa: Pyridoxal-5-phosphate (PLP) Levels

    Up to 90 Months

  • Effect of SC Asfotase Alfa on Growth: Weight Z-scores

    Up to 90 Months

  • Effect of SC Asfotase Alfa on Growth: Height/Length Z-scores

    Up to 90 Months

  • Effect of SC Asfotase Alfa on Respiratory Function

    Up to 90 Months

Study Arms (1)

asfotase alfa

EXPERIMENTAL

An initial single intravenous (IV) infusion of 2 mg/kg asfotase alfa, followed by subcutaneous (SC) injections of 1 mg/kg asfotase alfa 3 times per week

Biological: asfotase alfa

Interventions

asfotase alfaBIOLOGICAL
Also known as: ENB-0040
asfotase alfa

Eligibility Criteria

Age24 Weeks - 42 Months
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17)

You may qualify if:

  • 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

You may not qualify if:

  • 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)

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (8)

Alfred I. DuPont Hospital for Children

Wilmington, Delaware, 19803, United States

Location

St. John's Medical Research Institute

Springfield, Missouri, 65807, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

St. Vincent Hospital

Green Bay, Wisconsin, 54301, United States

Location

Tawam Hospital

Al Ain City, Abu Dhabi Emirate, United Arab Emirates

Location

Royal Maternity Hospital, Royal Belfast Hospital for Sick Children

Belfast, Northern Ireland, Bt126BB, United Kingdom

Location

Sheffield Children's Hospital

Sheffield, S10 2TH, United Kingdom

Location

Related Publications (3)

  • 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.

    PMID: 32762706DERIVED

  • 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.

    PMID: 30558909DERIVED

  • 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.

    PMID: 26529632DERIVED

Related Links

MeSH Terms

Conditions

HypophosphatasiaBone DiseasesRicketsOsteomalacia

Interventions

asfotase alfa

Condition Hierarchy (Ancestors)

Metal Metabolism, Inborn ErrorsMetabolism, Inborn ErrorsGenetic Diseases, InbornCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesMetabolic DiseasesNutritional and Metabolic DiseasesMusculoskeletal DiseasesBone Diseases, MetabolicCalcium Metabolism DisordersVitamin D DeficiencyAvitaminosisDeficiency DiseasesMalnutritionNutrition Disorders

Results Point of Contact

Title
Director of Clinical Trials
Organization
Alexion Pharmaceuticals, Inc.
ClinicalTrials@alexion.com
475-230-2596

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
LTE60
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

September 17, 2010

First Posted

September 20, 2010

Study Start

April 1, 2009

Primary Completion

August 1, 2016

Study Completion

August 1, 2016

Last Updated

March 13, 2019

Results First Posted

November 17, 2017

Record last verified: 2019-03

Locations

US(5)AE(1)GB(2)