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Safety and Efficacy Study of Asfotase Alfa in Adolescents and Adults With Hypophosphatasia (HPP)
This study has been completed.
Sponsor:
Alexion Pharma GmbH
Information provided by (Responsible Party):
Alexion Pharma GmbH
ClinicalTrials.gov Identifier:
NCT01163149
First received: June 24, 2010
Last updated: August 3, 2016
Last verified: August 2016
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Purpose
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 two doses of the study drug called asfotase alfa as compared to a control group to see what effects it has adolescents and adults with HPP.
| Condition | Intervention | Phase |
|---|---|---|
| Hypophosphatasia | Drug: asfotase alfa | Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Intervention Model: Parallel Assignment Masking: None (Open Label) Primary Purpose: Treatment |
| Official Title: | A Randomized, Open-Label, Multicenter, Multinational, Dose-Ranging, Concurrent Control Study of the Safety, Efficacy, Pharmacokinetic of ENB-0040 (Human Recombinant Tissue Nonspecific Alkaline Phosphatase Fusion Protein) in Adolescents and Adults With Hypophosphatasia (HPP) |
Resource links provided by NLM:
Genetics Home Reference related topics:
hypophosphatasia
Drug Information available for:
Asfotase alfa
U.S. FDA Resources
Further study details as provided by Alexion Pharma GmbH:
Primary Outcome Measures:
- Effect of asfotase alfa on reduction in plasma inorganic pyrophosphate (PPi) and plasma pyridoxal-5' phosphate (PLP) [ Time Frame: Week 24 ]Blood samples will be collected to evaluate the effect of Asfotase Alfa on reduction in plasma inorganic pyrophosphate (PPi) and plasma pyridoxal-5' phosphate (PLP)
- Safety and Tolerability of asfotase alfa [ Time Frame: Up to 96 weeks or until regulatory approval ]The safety and tolerability of daily subcutaneous (SC) injections of asfotase alfa will be assessed by routine monitoring of patients for adverse events (AEs) and injection-associated reactions (IARs) and monitoring changes from Baseline in physical examination findings, vital signs, clinical laboratory evaluations, renal ultrasound findings, funduscopic examinations, antibody evaluations, and results of pregnancy testing (in women of childbearing potential only). Monitoring for changes in concomitant medications and therapies will also occur.
Secondary Outcome Measures:
- Change in bone mineral content and density as measured by dual-energy X-ray absorptiometry (DXA) [ Time Frame: Every 24 weeks ]A DXA scan will be performed to evaluate bone mineral content and density of the spine, hip, and whole body.
- Change in walking ability as measured by the Six-Minute Walk Test (6MWT) [ Time Frame: Every 24 weeks ]The patient will be instructed to walk the length of a pre-measured hallway for 6 minutes. The primary measurement will be the distance walked (in meters).
- Change in HPP-related osteomalacia as measured by trans-iliac crest bone biopsy [ Time Frame: Week 24, Week 48 ]A trans-iliac crest bone biopsy will be performed to quantify osteomalacia severity.
| Enrollment: | 19 |
| Study Start Date: | June 2010 |
| Study Completion Date: | June 2016 |
| Primary Completion Date: | June 2016 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Cohort 1
Cohort 1: Daily SC injections of 0.3 mg/kg asfotase alfa (2.1 mg/kg/week total)
|
Drug: asfotase alfa
Cohort 1: Daily SC injections of 0.3 mg/kg asfotase alfa (tota1 of 2.1 mg/kg/week)
|
|
Experimental: Cohort 2
Cohort 2: Daily SC injections of 0.5 mg/kg asfotase alfa (3.5 mg/kg/week total)
|
Drug: asfotase alfa
Cohort 2: Daily SC injections of 0.5 mg/kg Asfotase Alfa (3.5 mg/kg/week total)
|
|
No Intervention: Concurrent Control
Following completion of the Week 24 visit, all patients (including those randomized to the concurrent control cohort) may be eligible to participate in an open-label extension study of asfotase alfa. In this extension period, all patients will be treated with daily SC injections of 0.5 mg/kg/day asfotase alfa (a total of 3.5 mg/kg/week) for approximately 24 weeks, then subjects will receive 1 mg/kg/day 6 days/week for an additional 48 weeks or until regulatory approval of the drug.
|
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| Ages Eligible for Study: | 13 Years to 65 Years (Child, Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion criteria:
Patients must meet all of the following inclusion criteria to be eligible for participation in this study:
- Patients or their legal representative(s) must provide written informed consent prior to undergoing any study-related procedures
- Patients must be ≥ 13 and ≤ 65 years of age at the time of study enrollment
- Female patients of childbearing potential and sexually mature males must agree to use a medically acceptable form of birth control; for the purposes of this study, females are considered of non-childbearing potential if they are surgically sterile (i.e., have undergone a total hysterectomy, bilateral salpingo-oophorectomy or tubal ligation) or are post-menopausal, defined as having complete cessation of menstruation for at least 1 year after 45 years of age
-
Patients must have a pre-established clinical diagnosis of HPP as indicated by:
- Serum alkaline phosphatase (ALP) below the age-adjusted normal range
- Plasma PLP at least twice the upper limit of normal (no vitamin B6 administered for at least 1 week prior to determination)
- Evidence of osteopenia or osteomalacia on skeletal radiographs
- Patients must have osteomalacia on bone biopsy, characterized by an MLT z-score of +2 or more (results from ENB-001-08 may be used)
- Patients must be willing to comply with study procedures and the visit schedule
Exclusion criteria:
Patients will be excluded from participation in this study if they meet any of the following exclusion criteria:
- Women who are pregnant or lactating
- History of sensitivity to tetracycline
- Serum calcium or phosphate levels below the normal range
- Serum 25(OH) vitamin D below 20 ng/mL
- Serum creatinine or parathyroid hormone (PTH) levels above the upper limit of normal
- 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
- Orthopedic surgery within 12 months prior to study entry that may interfere with the ability to perform functional assessments for the study
- Prior treatment with bisphosphonates within 2 years of study entry for any length of time or for more than 2 years at any time point; for patients with prior bisphosphonate use that is allowed, the bone resorption markers serum C-telopeptide and urine N-telopeptide or urine deoxypyridinoline must also be within the normal range or elevated to be eligible for study participation
- Treatment with 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
Contacts and Locations
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To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01163149
Please refer to this study by its ClinicalTrials.gov identifier: NCT01163149
Locations
| United States, Missouri | |
| Shriner's Hospital for Children | |
| St. Louis, Missouri, United States, 63131 | |
| United States, North Carolina | |
| Duke University Medical Center | |
| Durham, North Carolina, United States, 27710 | |
| Canada, Manitoba | |
| Health Sciences Centre Winnipeg, University of Manitoba | |
| Winnipeg, Manitoba, Canada, R3A 1S1 | |
Sponsors and Collaborators
Alexion Pharma GmbH
More Information
Additional Information:
Publications:
| Responsible Party: | Alexion Pharma GmbH |
| ClinicalTrials.gov Identifier: | NCT01163149 History of Changes |
| Other Study ID Numbers: |
ENB-009-10 |
| Study First Received: | June 24, 2010 |
| Last Updated: | August 3, 2016 |
Keywords provided by Alexion Pharma GmbH:
|
Hypophosphatasia HPP Bone Disease Soft Bones Low Alkaline Phosphatase |
genetic metabolic disorder alkaline phosphatase tissue-specific alkaline phosphatase (TNSALP) rickets osteomalacia |
Additional relevant MeSH terms:
|
Hypophosphatasia Metal Metabolism, Inborn Errors Metabolism, Inborn Errors Genetic Diseases, Inborn |
Metabolic Diseases Immunoglobulin G Immunologic Factors Physiological Effects of Drugs |
ClinicalTrials.gov processed this record on August 22, 2017