NCT00739505

Brief Summary

This clinical trial studies the safety, tolerability, and pharmacology of asfotase alfa when given to adults with HPP.

Trial Health

90
On Track

Trial Health Score

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

Enrollment
6

participants targeted

Target at below P25 for phase_1

Timeline
Completed

Started Aug 2008

Shorter than P25 for phase_1

Geographic Reach
2 countries

3 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

August 1, 2008

Completed
18 days until next milestone

First Submitted

Initial submission to the registry

August 19, 2008

Completed
2 days until next milestone

First Posted

Study publicly available on registry

August 21, 2008

Completed
4 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2009

Completed
1 month until next milestone

Study Completion

Last participant's last visit for all outcomes

February 1, 2009

Completed
Last Updated

March 29, 2019

Status Verified

March 1, 2019

Enrollment Period

5 months

First QC Date

August 19, 2008

Last Update Submit

March 28, 2019

Conditions

Hypophosphatasia (HPP)

Keywords

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

Outcome Measures

Primary Outcomes (1)

  • To determine the safety and tolerability of Asfotase Alfa given intravenously and given subcutaneously.

    Within the first 2 months (8 weeks).

Secondary Outcomes (2)

  • To assess the pharmacokinetics (PK) of Asfotase Alfa given intravenously and subcutaneously

    Within the first 2 months (8 weeks)

  • To assess the bioavailability of the subcutaneous Asfotase Alfa

    Within the first 2 months (8 weeks)

Study Arms (2)

Cohort 1

EXPERIMENTAL

3 HPP patients are to be enrolled in Cohort 1 and receive a single IV dose and three weekly SC doses of Asfotase Alfa . End of Study for patients in Cohort 1 is at 8 weeks.

Biological: Asfotase Alfa

Cohort 2

EXPERIMENTAL

Cohort 2 will begin when the safety and PK data for Cohort 1 weeks 1-4 has been reviewed by the DSMB. Cohort 2 will enroll 3 HPP patients and will receive a higher dose level than Cohort 1. Cohort 2 patients will have a single IV dose and three weekly SC doses of Asfotase Alfa . End of Study for patients in Cohort 2 is at 8 weeks.

Biological: Asfotase Alfa

Interventions

Asfotase AlfaBIOLOGICAL

The initial IV dose to be administered to patients was set at one-tenth the no adverse effect level (NOAEL) as determined by one month toxicology studies in animals in which Asfotase Alfa was administered as a single weekly IV dose. The SC doses to be administered are lower than the IV doses and are thought to be near or at the anticipated daily efficacious dose. Dosing will be as follows: Cohort 1: In Week 1, patients will receive an IV infusion of Asfotase Alfa at a dose of 3 mg/kg. In Weeks 2, 3 and 4, patients will receive weekly SC injections of Asfotase Alfa at a dose of 1 mg/kg SC.

Cohort 1

Eligibility Criteria

Age18 Years - 80 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • In order to qualify for participation, patients must meet all of the following criteria:
  • Patients must provide written informed consent, including privacy authorization, prior to participation.
  • Women of childbearing potential must sign the Women of Childbearing Potential Addendum and must be using an acceptable method of birth control. Women considered not of childbearing potential must be surgically sterile (total hysterectomy, bilateral salpingo-oophorectomy, or tubal ligation) or post-menopausal, which is defined as a complete cessation of menstruation for at least one year after the age of 45 years. All women must have a serum pregnancy test conducted at Screening prior to enrollment and the results must be negative.
  • Be between 18 and 80 years of age at the time of consent
  • Patients must be medically stable in the opinion of the Investigator.
  • Patients must be willing to comply with study procedures and the visit schedule.
  • Pre-established clinical diagnosis of HPP as indicated by:
  • a. Serum alkaline phosphatase at least 3 SD below the mean for age
  • b. Radiologic evidence of osteopenia or osteomalacia
  • c. Two or more HPP-related findings:
  • i. Plasma pyridoxal 5'-phosphate at least 2.5 SD above the mean (no vitamin B6 administered for at least 1 week prior to determination
  • ii. History of rickets
  • iii. History of premature loss of deciduous teeth
  • iv. Bone deformity consistent with osteomalacia or past history of rickets
  • v. History of any one of the following:
  • +3 more criteria

You may not qualify if:

  • In order to qualify for participation, patients must not meet any of the following criteria:
  • Women who are pregnant or lactating.
  • History of sensitivity to any of the constituents of the study drug.
  • Low levels of serum calcium, magnesium or phosphate.
  • Serum 25(OH) vitamin D level below 9.2 ng/mL.
  • Elevated serum creatinine or parathyroid hormone level.
  • Known cause of hypophosphatasemia other than HPP.
  • Current or prior clinically significant cardiac, endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, renal condition and/or other major disease which, in the opinion of the investigator, precludes study participation.
  • Treatment with a bisphosphonate or parathyroid hormone (PTH) within 6 months prior to the start of Asfotase Alfa administration.
  • Participation in an interventional or investigational drug study within 30 days prior to study participation.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (3)

Barnes Jewish Hospital- Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Department of Pediatrics & Child Health, Health Sciences Centre Winnipeg, University of Manitoba

Winnipeg, Manitoba, R3A 1S1, Canada

Location

Related Publications (2)

  • 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

  • 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.

    PMID: 18318644BACKGROUND

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

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

August 19, 2008

First Posted

August 21, 2008

Study Start

August 1, 2008

Primary Completion

January 1, 2009

Study Completion

February 1, 2009

Last Updated

March 29, 2019

Record last verified: 2019-03

Locations

CA(1)US(2)