Clinical trial NCT00739505: Safety Study of Human Recombinant Tissue Non-Specific Alkaline Phosphatase Fusion Protein Asfotase Alfa in Adults With Hypophosphatasia (HPP)
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hypophosphatasia (HPP)
Keywords: Hypophosphatasia
Bone Disease
Soft Bones
Low Alkaline Phosphatase
genetic metabolic disorder
alkaline phosphatase
tissue non-specific alkaline phosphatase
rickets
osteomalacia
Lead sponsor: Alexion Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2008-08-21
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

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.

Eligibility criteria: Inclusion Criteria:

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:

      * 1. Non-traumatic fracture
      * 2. Pseudofracture
      * 3. Non-healing fracture

Exclusion Criteria:

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.

Primary outcomes:
measure: To determine the safety and tolerability of Asfotase Alfa given intravenously and given subcutaneously.
timeFrame: Within the first 2 months (8 weeks).
Secondary outcomes:
measure: To assess the pharmacokinetics (PK) of Asfotase Alfa given intravenously and subcutaneously
timeFrame: Within the first 2 months (8 weeks)
measure: To assess the bioavailability of the subcutaneous Asfotase Alfa
timeFrame: Within the first 2 months (8 weeks)
Other outcomes:
Locations:
city: Saint Louis
country: United States
facility: Barnes Jewish Hospital- Washington University School of Medicine
state: Missouri
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Winnipeg
country: Canada
facility: Department of Pediatrics & Child Health, Health Sciences Centre Winnipeg, University of Manitoba
state: Manitoba
Study officials:
References:
citation: 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.
citation: 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.