NCT00952484

Brief Summary

This clinical trial studied the safety and efficacy of asfotase alfa in children with HPP compared to a historical control group.

Trial Health

90
On Track

Trial Health Score

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

Enrollment
13

participants targeted

Target at below P25 for phase_2

Timeline
Completed

Started Sep 2009

Shorter than P25 for phase_2

Geographic Reach
2 countries

2 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

First Submitted

Initial submission to the registry

August 3, 2009

Completed
3 days until next milestone

First Posted

Study publicly available on registry

August 6, 2009

Completed
26 days until next milestone

Study Start

First participant enrolled

September 1, 2009

Completed
10 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 1, 2010

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

July 1, 2010

Completed
1.1 years until next milestone

Results Posted

Study results publicly available

July 26, 2011

Completed
Last Updated

April 1, 2019

Status Verified

March 1, 2019

Enrollment Period

10 months

First QC Date

August 3, 2009

Results QC Date

May 14, 2011

Last Update Submit

March 28, 2019

Conditions

Hypophosphatasia (HPP)

Keywords

HypophosphatasiaHPPBone DiseaseSoft BonesLow Alkaline Phosphatasegenetic metabolic disorderalkaline phosphatasetissue non-specific alkaline phosphatasericketsosteomalacia

Outcome Measures

Primary Outcomes (1)

  • Change in Rickets Severity on Skeletal Radiographs From Baseline to Week 24 as Measured by the Radiographic Global Impression of Change (RGI-C) Scale

    A 7-point RGI-C (radiographic global impression of change) score was used to rate change in rickets severity. 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.

    Baseline and Week 24

Secondary Outcomes (12)

  • Change in Osteomalacia - Osteoid Thickness (as Measured by Trans-iliac Crest Bone Biopsy)

    Baseline and Week 24

  • Change in Osteomalacia - Osteoid Volume/Bone Volume (as Measured by Trans-iliac Crest Bone Biopsy)

    Baseline and Week 24

  • Change in Osteomalacia - Mineralization Lag Time (as Measured by Trans-iliac Crest Bone Biopsy)

    Baseline and Week 24

  • Change in Height (Z-scores)

    Baseline and Week 24

  • Change in Biomarkers of Asfotase Alfa Activity as Measured by Plasma Inorganic Pyrophosphate (PPi)

    Baseline and Week 24

  • +7 more secondary outcomes

Study Arms (2)

2 mg/kg

ACTIVE COMPARATOR

2 mg/kg subcutaneous injection three times per week.

Biological: asfotase alfa

3 mg/kg

ACTIVE COMPARATOR

3 mg/kg subcutaneous injection three times per week.

Biological: asfotase alfa

Interventions

asfotase alfaBIOLOGICAL

2 mg/kg subcutaneous injection three times per week for 6 months.

Also known as: Human Recombinant Tissue Nonspecific Alkaline Phosphatase Fusion Protein, sALP-Fc-D10
2 mg/kg

Eligibility Criteria

Age5 Years - 12 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17)

You may qualify if:

  • Written informed consent from parent or legal guardian prior to participation
  • Patients \> 5 and \< 12 years of age with open growth plates at time of enrollment
  • Tanner stage of 2 or less indicating pre-pubescence
  • Documented history of HPP, as evidenced by:
  • Presence of HPP-related rickets on skeletal radiographs of the wrist and knee
  • Serum alkaline phosphatase (ALP) below age-adjusted normal range
  • Plasma PLP at least twice the upper limit of normal
  • (OH) vitamin D level \> 20 ng/mL
  • Ability of patient and parent/guardian to comply with study requirements

You may not qualify if:

  • Serum calcium or phosphorus below age-adjusted normal range
  • History of sensitivity to any study drug constituent
  • Medical condition, serious intercurrent illness, or other extenuating circumstance that, in the opinion of the Investigator, may significantly interfere with study compliance, including all prescribed evaluations and follow-up activities
  • Treatment with an investigational drug within 1 month before start of study drug
  • Current enrollment in any other study involving an investigational new drug, device, or treatment for HPP (e.g., bone marrow transplantation)
  • Current evidence of a treatable form of rickets
  • Prior treatment with bisphosphonates
  • Bone fracture or orthopedic surgery within the past 12 months that, in the opinion of the Investigator would interfere with the ability of study patient to comply with study protocol
  • Major congenital abnormality other than those associated with HPP

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

Shriners Hospital for Children

St Louis, Missouri, 63131, United States

Location

The University of Manitoba Health Services Centre

Winnipeg, Manitoba, R3A 1S1, Canada

Location

Related Publications (3)

  • 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: 18086009BACKGROUND

  • Simmons JH, Rush ET, Petryk A, Zhou S, Martos-Moreno GA. Dual X-ray absorptiometry has limited utility in detecting bone pathology in children with hypophosphatasia: A pooled post hoc analysis of asfotase alfa clinical trial data. Bone. 2020 Aug;137:115413. doi: 10.1016/j.bone.2020.115413. Epub 2020 May 14.

    PMID: 32417537DERIVED

  • Whyte MP, Madson KL, Phillips D, Reeves AL, McAlister WH, Yakimoski A, Mack KE, Hamilton K, Kagan K, Fujita KP, Thompson DD, Moseley S, Odrljin T, Rockman-Greenberg C. Asfotase alfa therapy for children with hypophosphatasia. JCI Insight. 2016 Jun 16;1(9):e85971. doi: 10.1172/jci.insight.85971.

    PMID: 27699270DERIVED

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
Alexion Pharma GmbH
Organization
Alexion Pharma GmbH
ClinicalTrials@alxn.com
(617) 494-1393

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
LTE60
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

August 3, 2009

First Posted

August 6, 2009

Study Start

September 1, 2009

Primary Completion

July 1, 2010

Study Completion

July 1, 2010

Last Updated

April 1, 2019

Results First Posted

July 26, 2011

Record last verified: 2019-03

Locations

US(1)CA(1)