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HypophosphatasiaPhase 2NCT01205152

Extension Study of Protocol ENB-002-08 - Study of Asfotase Alfa in Infants and Young Children With Hypophosphatasia (HPP)

A Phase 2 study testing asfotase alfa in people with Hypophosphatasia, run by Alexion Pharmaceuticals, Inc. at 8 sites in 3 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 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). Read more about this study

Who is it for?
Ages 24 weeks to 42 months
Conditions the study is for
Hypophosphatasia
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
10 participants
Where
8 sitesin 3 countries
Study dates
Apr 2009to Aug 2016
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 24 weeks to 42 months
  • All sexes
  • No healthy volunteers
  • Child

Who may be able to join

  • 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

Who cannot join

  • 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)

Trial locations and contacts

8 sites in 3 countries.

8 sites in 3 countries

United States5 sites

  • St. Vincent Hospital

    Green Bay, Wisconsin, 54301

  • Vanderbilt University Medical Center

    Nashville, Tennessee, 37232

  • University of Nebraska Medical Center

    Omaha, Nebraska, 68198

  • St. John's Medical Research Institute

    Springfield, Missouri, 65807

  • Alfred I. DuPont Hospital for Children

    Wilmington, Delaware, 19803

Other trials in United States

United Kingdom2 sites

  • Royal Maternity Hospital, Royal Belfast Hospital for Sick Children

    Belfast, Northern Ireland, Bt126BB

  • Sheffield Children's Hospital

    Sheffield, S10 2TH

Other trials in United Kingdom

United Arab Emirates1 site

  • Tawam Hospital

    Al Ain City, Abu Dhabi Emirate

Other trials in United Arab Emirates

About this study

Official title: Extension Study of ENB-0040 (Human Recombinant Tissue-Nonspecific Alkaline Phosphatase Fusion Protein) in Severely Affected Infants and Young Children With Hypophosphatasia (HPP)

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).

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 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, 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 ENB-0040

Study groups in NCT01205152
Study groupRoleWhat they receive
asfotase alfaExperimentalAn 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
Receives: Biological: asfotase alfa

What is being measured

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

  1. 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.

    Measured: 84 months

  2. 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.

    Measured: Up to 90 Months

Secondary outcomes (5)

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

    Outcome measure is the change from Baseline in plasma inorganic pyrophosphate (PPi) levels. The time period is pre-dose (Baseline from the ENB-002-08 study [NCT00744042]) 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.

    Measured: Up to 90 Months

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

    Outcome measure is the change from Baseline in pyridoxal-5-phosphate (PLP) levels. The time period is pre-dose (Baseline from the ENB-002-08 study [NCT00744042]) 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.

    Measured: Up to 90 Months

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

    Outcome measure is the change from Baseline in Z-scores for weight. The time period is pre-dose (Baseline from the ENB-002-08 study [NCT00744042]) to the last assessment in the ENB-003-08 study, which represents up to 90 months of exposure in the combined studies.

    Measured: Up to 90 Months

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

    Outcome measure is the change from Baseline in Z-scores for height/length. The time period is pre-dose (Baseline from the ENB-002-08 study [NCT00744042]) to the last assessment in the ENB-003-08 study, which represents up to 90 months of exposure in the combined studies.

    Measured: Up to 90 Months

  5. Effect of SC Asfotase Alfa on Respiratory Function

    Outcome measure is the shift in the proportion of patients requiring respiratory support at their last assessment in Study ENB-003-08 compared with Baseline. The time period is pre-dose (Baseline from the ENB-002-08 study [NCT00744042]) to the last assessment in the ENB-003-08 study, which represents up to 90 months of exposure in the combined studies.

    Measured: Up to 90 Months

Timeline

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

  1. First posted20 Sep 2010 (estimated)
  2. Study startApr 2009
  3. Primary completionAug 2016
  4. Study completionAug 2016

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
10 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01205152
Sponsor's protocol ID
ENB-003-08
Other IDs
FD-R-003745-03
Status last verified
Mar 2019
First submitted
17 Sep 2010
Last updated
13 Mar 2019
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • 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.

    PubMed 32762706

  • 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.

    PubMed 30558909

  • 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.

    PubMed 26529632

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing asfotase alfa in people with Hypophosphatasia, run by Alexion Pharmaceuticals, Inc. at 8 sites in 3 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 3 inclusion and 3 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 13 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 8 sites in United States, United Kingdom, United Arab Emirates. 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 17 Nov 2017). 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?

Long-term Tolerability of Subcutaneous (SC) Asfotase Alfa (time frame: 84 months). The study lists 2 primary outcomes in all. 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 NCT01205152, 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 13 Mar 2019.

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