Hypophosphatasia (HPP)Phase 1NCT00739505
Safety Study of Human Recombinant Tissue Non-Specific Alkaline Phosphatase Fusion Protein Asfotase Alfa in Adults With Hypophosphatasia (HPP)
A Phase 1 study testing Asfotase Alfa in people with Hypophosphatasia (HPP), run by Alexion Pharmaceuticals, Inc. at 3 sites in 2 countries.
Trial summary
This clinical trial studies the safety, tolerability, and pharmacology of asfotase alfa when given to adults with HPP. Read more about this study
- Who is it for?
- Ages 18 to 80 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
- 6 participants
- Where
- 3 sitesin 2 countries
- Study dates
- Aug 2008to Feb 2009
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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
Who cannot join
- 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.
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- 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.
Trial locations and contacts
3 sites in 2 countries.
3 sites in 2 countries
United States2 sites
Duke University Medical Center
Durham, North Carolina, 27710
Barnes Jewish Hospital- Washington University School of Medicine
St Louis, Missouri, 63110
Canada1 site
Department of Pediatrics & Child Health, Health Sciences Centre Winnipeg, University of Manitoba
Winnipeg, Manitoba, R3A 1S1
About this study
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)
This clinical trial studies the safety, tolerability, and pharmacology of asfotase alfa when given to adults with HPP.
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.
- Conditions
- Hypophosphatasia (HPP)
- Being tested
- Asfotase Alfa
- Keywords
- Hypophosphatasia, 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
The initial IV dose to be administered to patients was set at one-tenth the no adverse effect level (NOAEL) as determined by one month toxicology studies in animals in which Asfotase Alfa was administered as a single weekly IV dose. The SC doses to be administered are lower than the IV doses and are thought to be near or at the anticipated daily efficacious dose. Dosing will be as follows:
Cohort 1: In Week 1, patients will receive an IV infusion of Asfotase Alfa at a dose of 3 mg/kg. In Weeks 2, 3 and 4, patients will receive weekly SC injections of Asfotase Alfa at a dose of 1 mg/kg SC.
Asfotase AlfaBiological
Cohort 2: In Week 1, patients will receive an IV infusion of Asfotase Alfa at a dose of 7 mg/kg. In Weeks 2, 3 and 4, patients will receive weekly SC injections of Asfotase Alfa at a dose of 1.5 mg/kg SC.
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 | Experimental | 3 HPP patients are to be enrolled in Cohort 1 and receive a single IV dose and three weekly SC doses of Asfotase Alfa . End of Study for patients in Cohort 1 is at 8 weeks. Receives: Biological: Asfotase Alfa |
| Cohort 2 | Experimental | Cohort 2 will begin when the safety and PK data for Cohort 1 weeks 1-4 has been reviewed by the DSMB. Cohort 2 will enroll 3 HPP patients and will receive a higher dose level than Cohort 1. Cohort 2 patients will have a single IV dose and three weekly SC doses of Asfotase Alfa . End of Study for patients in Cohort 2 is at 8 weeks. Receives: Biological: Asfotase Alfa |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine the safety and tolerability of Asfotase Alfa given intravenously and given subcutaneously.
Measured: Within the first 2 months (8 weeks).
Secondary outcomes (2)
To assess the pharmacokinetics (PK) of Asfotase Alfa given intravenously and subcutaneously
Measured: Within the first 2 months (8 weeks)
To assess the bioavailability of the subcutaneous Asfotase Alfa
Measured: Within the first 2 months (8 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Aug 2008 (estimated)
- Study startAug 2008
- Primary completionJan 2009
- Study completionFeb 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Hypophosphatasia (HPP)Studies of the same condition, open and under way.
- More trials run by Alexion Pharmaceuticals, Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- Alexion Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00739505
- Sponsor's protocol ID
- ENB-001-08
- Status last verified
- Mar 2019
- First submitted
- 19 Aug 2008
- Last updated
- 29 Mar 2019
- Results posted
- No
- 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 18086009Drake 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.
PubMed 18318644
Study at a glance
From the registry record, last updated by the sponsor on 29 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT00739505
- Acronym / sponsor ID
- ENB-001-08
- Conditions
- Hypophosphatasia (HPP)
- Keywords
- Hypophosphatasia, Bone Disease, Soft Bones, Low Alkaline Phosphatase, genetic metabolic disorder, alkaline phosphatase, tissue non-specific alkaline phosphatase, rickets
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 6 participants (actual)
- Lead sponsor
- Alexion Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- Aug 2008
- Primary completion
- Jan 2009 (actual)
- Study completion
- Feb 2009 (actual)
- First posted
- 21 Aug 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 | Experimental | Biological: Asfotase Alfa3 HPP patients are to be enrolled in Cohort 1 and receive a single IV dose and three weekly SC doses of Asfotase Alfa . End of Study for patients in Cohort 1 is at 8 weeks. |
| Cohort 2 | Experimental | Biological: Asfotase AlfaCohort 2 will begin when the safety and PK data for Cohort 1 weeks 1-4 has been reviewed by the DSMB. Cohort 2 will enroll 3 HPP patients and will receive a higher dose level than Cohort 1. Cohort 2 patients will have a single IV dose and three weekly SC doses of Asfotase Alfa . End of Study for patients in Cohort 2 is at 8 weeks. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- 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.
Key exclusion criteria (10 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Asfotase AlfaThe initial IV dose to be administered to patients was set at one-tenth the no adverse effect level (NOAEL) as determined by one month toxicology studies in animals in which Asfotase Alfa was administered as a single weekly IV dose. The SC doses to be administered are lower than the IV doses and are thought to be near or at the anticipated daily efficacious dose. Dosing will be as follows: Cohort 1: In Week 1, patients will receive an IV infusion of Asfotase Alfa at a dose of 3 mg/kg. In Weeks 2, 3 and 4, patients will receive weekly SC injections of Asfotase Alfa at a dose of 1 mg/kg SC. | Biological | Cohort 1 |
| Asfotase AlfaCohort 2: In Week 1, patients will receive an IV infusion of Asfotase Alfa at a dose of 7 mg/kg. In Weeks 2, 3 and 4, patients will receive weekly SC injections of Asfotase Alfa at a dose of 1.5 mg/kg SC. | Biological | Cohort 2 |
Primary outcome
To determine the safety and tolerability of Asfotase Alfa given intravenously and given subcutaneously.
Time frame: Within the first 2 months (8 weeks).
2 secondary outcomes
To assess the pharmacokinetics (PK) of Asfotase Alfa given intravenously and subcutaneously
Time frame: Within the first 2 months (8 weeks)
To assess the bioavailability of the subcutaneous Asfotase Alfa
Time frame: Within the first 2 months (8 weeks)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Mar 2019.
- Background: PubMed 18086009Millan 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.
- Background: PubMed 18318644Drake 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.
- Hypophosphatasia WebsiteLink provided by the sponsor.
- Hypophosphatasia Website for Healthcare ProvidersLink provided by the sponsor.
- HPP support groupLink provided by the sponsor.
- US Hypophosphatasia Group (Soft Bones)Link provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
3 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Asfotase Alfa in people with Hypophosphatasia (HPP), run by Alexion Pharmaceuticals, Inc. at 3 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 18 inclusion and 10 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 29 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 3 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
To determine the safety and tolerability of Asfotase Alfa given intravenously and given subcutaneously. (time frame: Within the first 2 months (8 weeks).). 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 NCT00739505, which also lists 2 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 29 Mar 2019.