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Hypophosphatasia (HPP)Phase 2NCT00952484

Safety and Efficacy of Asfotase Alfa in Juvenile Patients With Hypophosphatasia (HPP)

A Phase 2 study testing asfotase alfa in people with Hypophosphatasia (HPP), run by Alexion Pharmaceuticals, Inc. at 2 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 studied the safety and efficacy of asfotase alfa in children with HPP compared to a historical control group. Read more about this study

Who is it for?
Ages 5 to 12 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
13 participants
Where
2 sitesin 2 countries
Study dates
Sep 2009to Jul 2010
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 5 to 12 years
  • All sexes
  • No healthy volunteers
  • Child

Who may be able to join

  • 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
Show all 9Show fewer
  • Plasma PLP at least twice the upper limit of normal
  • 25(OH) vitamin D level > 20 ng/mL
  • Ability of patient and parent/guardian to comply with study requirements

Who cannot join

  • 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
Show all 9Show fewer
  • 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

Trial locations and contacts

2 sites in 2 countries.

2 sites in 2 countries

United States1 site

  • Shriners Hospital for Children

    St Louis, Missouri, 63131

Other trials in United States

Canada1 site

  • The University of Manitoba Health Services Centre

    Winnipeg, Manitoba, R3A 1S1

Other trials in Canada

About this study

Official title: A Randomized, Open-Label, Multicenter, Multinational, Dose-Ranging, Historical Control Study of the Safety, Efficacy, Pharmacokinetics, and Pharmacodynamics of ENB-0040 (Human Recombinant Tissue Nonspecific Alkaline Phosphatase Fusion Protein) in Children With Hypophosphatasia (HPP)

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

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.

Efficacy analyses were prospectively defined in the protocol with a comparison to historical controls. The historical control group came from patients whose characteristics matched as closely as possible the entry criteria for the trial. The control group included all patients who had x-rays within the age range defined by the inclusion criteria of this study (5 to 12 years of age, inclusive, with open growth plates).

The pre-specified plan for analysis was to combine the two asfotase alfa treated groups (asfotase alfa 2 mg/kg subcutaneous (SC) injection three times per week or 3 mg/kg subcutaneous (SC) injection three times per week) and compare them to historical controls.

Being tested
asfotase alfa
Keywords
Hypophosphatasia, HPP, 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

    Also called Human Recombinant Tissue Nonspecific Alkaline Phosphatase Fusion Protein, sALP-Fc-D10

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

  • asfotase alfaBiological

    Also called Human Recombinant Tissue Nonspecific Alkaline Phosphatase Fusion Protein, sALP-Fc-D10

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

Study groups in NCT00952484
Study groupRoleWhat they receive
2 mg/kgActive comparator2 mg/kg subcutaneous injection three times per week.
Receives: Biological: asfotase alfa
3 mg/kgActive comparator3 mg/kg subcutaneous injection three times per week.
Receives: Biological: asfotase alfa

What is being measured

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

  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.

    Measured: Baseline and Week 24

Secondary outcomes (12)

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

    Change from Baseline to Week 24 in osteoid thickness.

    Measured: Baseline and Week 24

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

    Change from Baseline to Week 24 in osteoid volume/bone volume (%), calculated as the absolute difference of the Baseline and Week 24 percentages.

    Measured: Baseline and Week 24

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

    Change from Baseline to Week 24 in mineralization lag time.

    Measured: Baseline and Week 24

  4. Change in Height (Z-scores)

    Change from Baseline to Week 24 in Height Z-Score. Height Z-Scores assigned based on Centers for Disease Control (CDC) growth charts and methodology.

    Measured: Baseline and Week 24

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

    Change from Baseline to Week 24 in Plasma PPi

    Measured: Baseline and Week 24

  6. Change in Biomarkers of Asfotase Alfa Activity as Measured by Pyridoxal-5'-Phosphate (PLP)

    Change from Baseline to Week 24 in Plasma PLP

    Measured: Baseline and Week 24

  7. Maximum Serum Concentration of Asfotase Alfa (Cmax).

    Maximum serum concentration observed following single dose of asfotase alfa.

    Measured: Study Week 1 (0 to 48 hours post-dose)

  8. Time at Maximum Serum Concentration of Asfotase Alfa (Tmax)

    Maximum serum concentration observed following single dose of asfotase alfa.

    Measured: Study Week 1 (0 to 48 hours post-dose)

  9. Area Under Serum Concentration-time Curve to Last Measurable Concentration of Asfotase Alfa (AUCt)

    Area under serum concentration-time curve to last measurable concentration following single dose of asfotase alfa.

    Measured: Study Week 1 (0 to 48 hours post-dose)

  10. Maximum Serum Concentration of Asfotase Alfa (Cmax).

    Maximum serum concentration observed following multiple doses of asfotase alfa.

    Measured: Study Week 6 (0 to 48 hours post-dose)

  11. Time at Maximum Serum Concentration of Asfotase Alfa (Tmax).

    Time at maximum serum concentration observed following multiple doses of asfotase alfa.

    Measured: Study Week 6 (0 to 48 hours post-dose)

  12. Area Under Serum Concentration-time Curve to Last Measurable Concentration of Asfotase Alfa (AUCt)

    Area under serum concentration-time curve to last measurable concentration following multiple doses of asfotase alfa.

    Measured: Study Week 6 (0 to 48 hours post-dose).

Timeline

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

  1. First posted6 Aug 2009 (estimated)
  2. Study startSep 2009
  3. Primary completionJul 2010
  4. Study completionJul 2010

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 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
13 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00952484
Sponsor's protocol ID
ENB-006-09
Status last verified
Mar 2019
First submitted
3 Aug 2009
Last updated
1 Apr 2019
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

  • 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.

    PubMed 32417537

  • 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.

    PubMed 27699270

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing asfotase alfa in people with Hypophosphatasia (HPP), run by Alexion Pharmaceuticals, Inc. at 2 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 9 inclusion and 9 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 1 Apr 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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

Are results available for this study?

Yes. Results are posted in the registry (first posted 26 Jul 2011). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Change in Rickets Severity on Skeletal Radiographs From Baseline to Week 24 as Measured by the Radiographic Global Impression of Change (RGI-C) Scale (time frame: Baseline and Week 24). 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 NCT00952484, which also lists 3 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 1 Apr 2019.

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