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Hypophosphatasia (HPP)Phase 1NCT00739505

Safety Study of Human Recombinant Tissue Non-Specific Alkaline Phosphatase Fusion Protein Asfotase Alfa in Adults With Hypophosphatasia (HPP)

A Phase 1 study testing Asfotase Alfa in people with Hypophosphatasia (HPP), run by Alexion Pharmaceuticals, Inc. at 3 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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

Who is it for?
Ages 18 to 80 years
Conditions the study is for
Hypophosphatasia (HPP)
What is being tested?
Asfotase Alfa
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
6 participants
Where
3 sitesin 2 countries
Study dates
Aug 2008to Feb 2009
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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:
  • 1. Non-traumatic fracture
  • 2. Pseudofracture
  • 3. Non-healing fracture

Who cannot join

  • 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.
Show all 10Show fewer
  • 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.

Trial locations and contacts

3 sites in 2 countries.

3 sites in 2 countries

United States2 sites

  • Duke University Medical Center

    Durham, North Carolina, 27710

  • Barnes Jewish Hospital- Washington University School of Medicine

    St Louis, Missouri, 63110

Other trials in United States

Canada1 site

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

    Winnipeg, Manitoba, R3A 1S1

Other trials in Canada

About this study

Official title: A Multicenter, Open-Label, Dose Escalating Study of the Safety, Tolerability and Pharmacology of Human Recombinant Tissue Non-Specific Alkaline Phosphatase Fusion Protein Asfotase Alfa in Adults With Hypophosphatasia (HPP)

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

Read the 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 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.

Being tested
Asfotase Alfa
Keywords
Hypophosphatasia, Bone Disease, Soft Bones, Low Alkaline Phosphatase, genetic metabolic disorder, alkaline phosphatase, tissue non-specific alkaline phosphatase, rickets, osteomalacia
Medical subject headings
Hypophosphatasia, Bone Diseases, Rickets, Osteomalacia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • 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.

  • Asfotase AlfaBiological

    Cohort 2: In Week 1, patients will receive an IV infusion of Asfotase Alfa at a dose of 7 mg/kg. In Weeks 2, 3 and 4, patients will receive weekly SC injections of Asfotase Alfa at a dose of 1.5 mg/kg SC.

Study groups in NCT00739505
Study groupRoleWhat they receive
Cohort 1Experimental3 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.
Receives: Biological: Asfotase Alfa
Cohort 2ExperimentalCohort 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.
Receives: Biological: Asfotase Alfa

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    Measured: Within the first 2 months (8 weeks).

Secondary outcomes (2)

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

    Measured: Within the first 2 months (8 weeks)

  2. To assess the bioavailability of the subcutaneous Asfotase Alfa

    Measured: Within the first 2 months (8 weeks)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Aug 2008 (estimated)
  2. Study startAug 2008
  3. Primary completionJan 2009
  4. Study completionFeb 2009

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
6 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00739505
Sponsor's protocol ID
ENB-001-08
Status last verified
Mar 2019
First submitted
19 Aug 2008
Last updated
29 Mar 2019
Results posted
No
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 18086009

  • 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.

    PubMed 18318644

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Asfotase Alfa in people with Hypophosphatasia (HPP), run by Alexion Pharmaceuticals, Inc. at 3 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 18 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 29 Mar 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

To determine the safety and tolerability of Asfotase Alfa given intravenously and given subcutaneously. (time frame: Within the first 2 months (8 weeks).). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00739505, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Mar 2019.

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