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Trial #NCT01176266
Hypophosphatasia Clinical Trials

Open-Label Study of Asfotase Alfa in Infants and Children = 5 Years of Age With Hypophosphatasia (HPP)


An Open-Label, Multicenter, Multinational Study of the Safety, Efficacy and Pharmacokinetics of Asfotase Alfa (Human Recombinant Tissue-nonspecific Alkaline Phosphatase Fusion Protein) in Infants and Children = 5 Years of Age With Hypophosphatasia (HPP)
Study ID: ENB-010-10; Source: Alexion Pharma International Sarl
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Definitions
Interventional trials
Determine whether experimental treatments or new ways of using known therapies are safe and effective under controlled environments.
Observational trials
Address health issues in large groups of people or populations in natural settings.
Recruiting
Participants are currently being recruited and enrolled.
Active, not recruiting
Study is ongoing (i.e., patients are being treated or examined), but enrollment has completed.
Not yet recruiting
Participants are not yet being recruited or enrolled.
Enrolling by invitation
Participants are being (or will be) selected from a predetermined population.
Completed
The study has concluded normally; participants are no longer being examined or treated (i.e., last patient's last visit has occurred).
Withdrawn
Study halted prematurely, prior to enrollment of first participant.
Suspended
Recruiting or enrolling participants has halted prematurely but potentially will resume.
Terminated
Recruiting or enrolling participants has halted prematurely and will not resume; participants are no longer being examined or treated.
Status Recruiting
Country Multiple Countries
Study type Interventional
Enrollment 60
Start date July 2010
Completion date December 2015
Phase Phase 2/Phase 3
Sponsor Alexion Pharma International Sarl
Summary:
This clinical trial is being conducted to study hypophosphatasia (HPP), a bone disorder
caused by gene mutations or changes. These gene mutations cause low levels of an enzyme
needed to harden bone. The purpose of this study is to test the safety and efficacy of a
study drug called asfotase alfa (human recombinant tissue non-specific alkaline phosphate
fusion protein) to see what effects it has on patients = 5 years of age or less with HPP.
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.
Eligibility:
Gender: Both
Age: N/A - 5 Years
Inclusion Criteria:
Patients must meet all of the following criteria for enrollment in this study:
- Parent or legal guardian(s) must provide written informed consent prior to any study procedures being performed and must be willing to comply with all study-required procedures
- Documented diagnosis of HPP as indicated by:
- Total serum alkaline phosphatase below the lower limit of normal for age
- Plasma PLP above the upper limit of normal (unless patient is receiving pyridoxine for seizures)
- Radiographic evidence of HPP, characterized by:
- Flared and frayed metaphyses
- Severe, generalized osteopenia
- Widened growth plates
- Areas of radiolucency or sclerosis
- Two or more of the following HPP-related findings:
- History or presence of:
- Nontraumatic post-natal fracture
- Delayed fracture healing
- Nephrocalcinosis or history of elevated serum calcium
- Functional craniosynostosis
- Respiratory compromise or rachitic chest deformity
- Vitamin B6 dependent seizures
- Failure to thrive
- Onset of symptoms prior to 6 months of age
- Chronological age or adjusted age for premature infants born = 37 weeks gestation of = 5 years
- Otherwise medically stable in the opinion of the Investigator and/or Sponsor
Exclusion criteria:
Patients will be excluded from enrollment in this study if they meet any of the following exclusion criteria:
- Clinically significant disease that precludes study participation, in the opinion of the Investigator and/or Sponsor
- Serum calcium or phosphate levels below the normal range
- Serum 25 hydroxy (25 [OH]) vitamin D below 20 ng/mL
- Current evidence of treatable form of rickets
- Prior treatment with bisphosphonates
- Treatment with an investigational drug within 1 month prior to the start of asfotase alfa treatment
- Current enrollment in any other study involving an investigational new drug, device or treatment for HPP (e.g., bone marrow transplantation)
NOTE: Historical values for PLP may be used to determine patient eligibility. Patients with low 25(OH) vitamin D levels are eligible for study participation after correction of levels with vitamin D supplementation.
Outcome:
Primary outcome
  • Effect of asfotase alfa treatment on skeletal manifestations of HPP
    Effect of asfotase alfa treatment on skeletal manifestations of HPP as measured by radiographs using a qualitative Radiographic Global Impression of Change (RGI-C) scale for all treated patients
    Time frame: Up to 48 months or until regulatory approval
  • Safety and tolerability of repeated subcutaneous (SC) injections of asfotase alfa
    Safety and tolerability of repeated subcutaneous (SC) injections of asfotase alfa for all treated patients
    Time frame: Up to 48 months or until regulatory approval
Secondary outcome
  • Effect of asfotase alfa treatment on physical growth
    Effect of asfotase alfa treatment on physical growth as measured by body weight, length, arm span, head circumference, and chest circumference for all treated patients
    Time frame: Up to 48 months or until regulatory approval
  • Effect of asfotase alfa on biomarkers
    Effect of asfotase alfa on plasma inorganic pyrophosphate (PPi) and plasma pyridoxal-5' phosphate (PLP)
    Time frame: Up to 48 months or until regulatory approval
  • Effect of asfotase alfa on serum parathyroid hormone (PTH)
    Effect of asfotase alfa on serum parathyroid hormone (PTH)
    Time frame: Up to 48 months or until regulatory approval
  • Effect of asfotase alfa treatment on respiratory function
    Effect of asfotase alfa treatment on respiratory function as measured by ventilator status, time on respiratory support (including time on ventilator or supplemental oxygen), ventilator rate or oxygen volume, ventilator pressures, and fraction of inspired oxygen (FiO2) for all treated patients
    Time frame: Up to 48 months or until regulatory approval
  • Effect of asfotase alfa treatment on tooth loss
    Effect of asfotase alfa treatment on tooth loss for all treated patients
    Time frame: Up to 48 months or until regulatory approval
  • Effect of asfotase alfa treatment on ventilator-free survival
    For patients who are not mechanically ventilated at the time of enrollment, the percentage who are alive and ventilator-free after receiving asfotase alfa as compared to an age-matched historical control group
    Time frame: Up to 48 months or until regulatory approval
  • Pharmacokinetic (PK) properties of asfotase alfa
    The PK properties of asfotase alfa
    Time frame: Up to 48 months or until regulatory approval
Contacts:
  • Alexion Pharma International Sàrl (Sponsor);
Location Country Status
Children's Hospital & Research Center Oakland Oakland, California United States Recruiting
Cincinnati Children's Hospital Medical Center Cincinnati, Ohio United States Recruiting
Children's Hospital of Pittsburgh of UPMC Pittsburgh, Pennsylvania United States Recruiting
Royal Children'S Hospital Parkville Victoria, Australia Recruiting
Health Sciences Centre Winnipeg, University of Manitoba Winnipeg, Manitoba Canada Recruiting
Necker Hospital Paris, France Recruiting
Chu de Toulouse Toulouse, France Recruiting
Universitätskinderklinik Würzburg Würzburg, Germany Recruiting
Istituto Giannina Gaslini Genova, Italy Recruiting
Ospedale Pediatrico Bambino Gesù Roma, Italy Recruiting
Fukuoka Higashi Medical Hospital Koga-city, Fukuoka Japan Recruiting
Ishikawa Prefectural Hospital Kanazawa-city, Ishikawa Japan Recruiting
Saitama Municipal Hospital Saitama-city, Saitama Japan Recruiting
Tokyo Medical University Hospital Shinjuku-ku, Tokyo Japan Recruiting
St. Marianna University School of Medicine, Yokohayama City Seibu Hospital Yokohama-city, Kanagawa, Yokohama-city Japan Recruiting
Hospital Infantil Universitario Nino Jesus Madrid, Spain Recruiting
National Taiwan University Hospital Taipei, Taiwan Recruiting
Uludag Universitesi Hastanesi Nilüfer, Bursa Turkey Recruiting
Birmingham Children's Hospital Birmingham, United Kingdom Recruiting
Royal Manchester Children'S Hospital Manchester, United Kingdom Recruiting
Sheffield Children'S Hospital Sheffield, United Kingdom Recruiting
Sponsors:
  • Alexion Pharma International Sarl - (Lead Sponsor)

Related trials: Terms
  • HPP
  • genetic metabolic disorder
  • Bone Disease
  • osteomalacia
  • alkaline phosphatase
  • rickets
  • Soft Bones
  • Low Alkaline Phosphatase
  • Hypophosphatasia
  • tissue-specific alkaline phosphatase (TNSALP)
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