Hypophosphatasia (HPP)Phase 1/2NCT00744042
Safety and Efficacy Study of Asfotase Alfa in Severely Affected Infants With Hypophosphatasia (HPP)
A Phase 1/2 study testing asfotase alfa in people with Hypophosphatasia (HPP), run by Alexion Pharmaceuticals, Inc. at 10 sites in 4 countries.
Trial summary
This clinical trial studies the safety and efficacy of asfotase alfa in infants and young children with infantile onset HPP. Read more about this study
- Who is it for?
- Ages Up to 36 months
- Conditions the study is for
- Hypophosphatasia (HPP)
- What is being tested?
- asfotase alfa
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 10 sitesin 4 countries
- Study dates
- Sep 2008to May 2010
- Phase
- Phase 1/2
- 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 Up to 36 months
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Legal guardian(s) must provide informed consent prior to any study procedures
- Documented diagnosis of severe HPP as indicated by:
- Total serum alkaline phosphatase at least 3 standard deviations (SD) below the mean for age
- Plasma pyridoxal 5'-phosphate (PLP) at least 4 times the upper limit of normal
- Radiographic evidence of HPP (hypophosphatasia), characterized by:
- Flared and frayed metaphyses
Show all 22Show fewer
- Severe, generalized osteopenia
- Widened growth plates
- One or more HPP-related findings:
- History or presence of:
- Non-traumatic post-natal fracture
- Delayed fracture healing
- History of elevated serum calcium
- Functional craniosynostosis with decreased head circumference growth
- Nephrocalcinosis
- Respiratory compromise
- Rachitic chest deformity and/or vitamin B6 dependent seizures
- Failure to thrive
- Onset of symptoms prior to 6 months of age
- Age ≤ 36 months
- Otherwise medically stable (patient may be on ventilatory support)
- Legal guardian(s) must be willing to comply with the study
Who cannot join
- History of sensitivity to any of the constituents of the study drug
- Current or prior clinically significant cardiovascular, endocrinologic, hematologic, hepatic, immunologic, metabolic, infectious, urologic, pulmonary, neurologic, dermatologic, renal condition and/or other major disease which, in the opinion of the investigator, precludes study participation
- Treatment with an investigational drug within 1 month prior to the start of study drug administration
- Current enrollment in any other study involving an investigational new drug, device or treatment for HPP (e.g., bone marrow transplantation)
- Low serum calcium, phosphate or 25(OH) vitamin D
- Current evidence of a treatable form of rickets
- Prior treatment with bisphosphonate
Trial locations and contacts
10 sites in 4 countries.
10 sites in 4 countries
United States6 sites
St. Vincent Hospital
Green Bay, Wisconsin, 54301
Arkansas Children's Hospital
Little Rock, Arkansas, 72202
Vanderbilt Children's Hospital
Nashville, Tennessee, 37232
University of Nebraska Medical Center, Munroe-Meyer Institute
Omaha, Nebraska, 68114
St. John's Hospital
Springfield, Missouri, 65804
Alfred I. duPont Hospital for Children
Wilmington, Delaware, 19803
United Kingdom2 sites
Royal Belfast Hospital for Sick Children
Belfast, Northern Ireland
Sheffield Children's Hospital
Sheffield, England, S10 2TH
Canada1 site
The University of Manitoba Health Sciences Centre
Winnipeg, Manitoba, R3A 1S1
United Arab Emirates1 site
Tawam-John Hopkins Hospital
Al Ain City, Abu Dhabi Emirate
About this study
Official title: A Multicenter, Open-Label Study of the Safety, Tolerability and Pharmacology of Asfotase Alfa in up to 10 Severely Affected Patients With for the Treatment of Severely Affected Patients With Infantile Hypophosphatasia (HPP)
This clinical trial studies the safety and efficacy of asfotase alfa in infants and young children with infantile onset HPP.
Read the detailed description
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, 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 Asfotase Alfa was formerly referred to as ENB-0040, Human Recombinant Tissue Nonspecific Alkaline Phosphatase Fusion Protein
| Study group | Role | What they receive |
|---|---|---|
| asfotase alfa | Other | asfotase alfa Receives: Biological: asfotase alfa |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Rickets Severity From Baseline to Week 24, Based on Assessment of Skeletal Radiographs Using Radiologic Global Impression of Change (RGI-C)
A 7-point RGI-C (Radiographic Global Impression of Change) score was used to rate change in rickets severity. Scores ranged from -3 (severe worsening of rickets) to +3 (complete healing of rickets). Only those patients with a minimum score of +2 indicating substantial healing of rickets) were considered "responders". Three pediatric radiologists not affiliated with the conduct of the study performed the ratings. Average scores were derived for each patient at each assessment.
Measured: 24 weeks
Secondary outcomes (3)
Maximum Serum Concentration of Asfotase Alfa (Cmax)
Maximum serum concentration observed during intensive PK sampling interval.
Measured: Study Week 1 (0 to 168 hours post-dose). Study Week 2 and Study Week 3 (0 to 48 hours post-dose)
Time at Maximum Serum Concentration of Asfotase Alfa (Tmax)
Time at maximum serum concentration observed during intensive PK sampling interval.
Measured: Study Week 1 (0 to 168 hours post-dose). Study Week 2 and Study Week 3 (0 to 48 hours post-dose).
Area Under Serum Concentration-time Curve to Last Measurable Concentration of Asfotase Alfa (AUCt)
Area under serum concentration-time curve to last measurable concentration during intensive PK sampling interval.
Measured: Study Week 1 (0 to 168 hours post-dose). Study Week 2 and Study Week 3 (0 to 48 hours post-dose).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Aug 2008 (estimated)
- Study startSep 2008
- Primary completionMay 2010
- Study completionMay 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (5)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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 11 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
- NCT00744042
- Sponsor's protocol ID
- ENB-002-08
- Status last verified
- Mar 2019
- First submitted
- 27 Aug 2008
- Last updated
- 1 Apr 2019
- Results posted
- Yes, on ClinicalTrials.gov
- 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 18318644Padidela 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 32762706Whyte 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 26529632Whyte MP, Greenberg CR, Salman NJ, Bober MB, McAlister WH, Wenkert D, Van Sickle BJ, Simmons JH, Edgar TS, Bauer ML, Hamdan MA, Bishop N, Lutz RE, McGinn M, Craig S, Moore JN, Taylor JW, Cleveland RH, Cranley WR, Lim R, Thacher TD, Mayhew JE, Downs M, Millan JL, Skrinar AM, Crine P, Landy H. Enzyme-replacement therapy in life-threatening hypophosphatasia. N Engl J Med. 2012 Mar 8;366(10):904-13. doi: 10.1056/NEJMoa1106173.
PubMed 22397652
Study at a glance
From the registry record, last updated by the sponsor on 1 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Open-Label Study of the Safety, Tolerability and Pharmacology of Asfotase Alfa in up to 10 Severely Affected Patients With for the Treatment of Severely Affected Patients With Infantile Hypophosphatasia (HPP)
- ClinicalTrials.gov ID
- NCT00744042
- Acronym / sponsor ID
- ENB-002-08
- Conditions
- Hypophosphatasia (HPP)
- Keywords
- Hypophosphatasia, HPP, Bone Disease, Soft Bones, Low Alkaline Phosphatase, genetic metabolic disorder, alkaline phosphatase, tissue non-specific alkaline phosphatase
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 11 participants (actual)
- Lead sponsor
- Alexion Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- Sep 2008
- Primary completion
- May 2010 (actual)
- Study completion
- May 2010 (actual)
- First posted
- 29 Aug 2008 (estimated)
- Results
- Posted 30 Sep 2011
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 and efficacy of asfotase alfa in infants and young children with infantile onset HPP.
Detailed description
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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| asfotase alfa | Other | Biological: asfotase alfaasfotase alfa |
Who may qualify
- Ages
- Up to 36 months
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (22 listed)
- Legal guardian(s) must provide informed consent prior to any study procedures
- Documented diagnosis of severe HPP as indicated by:
- Onset of symptoms prior to 6 months of age
- Age ≤ 36 months
- Otherwise medically stable (patient may be on ventilatory support)
Key exclusion criteria (7 listed)
- History of sensitivity to any of the constituents of the study drug
- Current or prior clinically significant cardiovascular, endocrinologic, hematologic, hepatic, immunologic, metabolic, infectious, urologic, pulmonary, neurologic, dermatologic, renal condition and/or other major disease which, in the opinion of the investigator, precludes study participation
- Treatment with an investigational drug within 1 month prior to the start of study drug administration
- Current enrollment in any other study involving an investigational new drug, device or treatment for HPP (e.g., bone marrow transplantation)
- Low serum calcium, phosphate or 25(OH) vitamin D
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 alfaAlso: Asfotase Alfa was formerly referred to as ENB-0040, Human Recombinant Tissue Nonspecific Alkaline Phosphatase Fusion Protein | Biological | asfotase alfa |
Primary outcome
Change in Rickets Severity From Baseline to Week 24, Based on Assessment of Skeletal Radiographs Using Radiologic Global Impression of Change (RGI-C)
Time frame: 24 weeks
A 7-point RGI-C (Radiographic Global Impression of Change) score was used to rate change in rickets severity. Scores ranged from -3 (severe worsening of rickets) to +3 (complete healing of rickets). Only those patients with a minimum score of +2 indicating substantial healing of rickets) were considered "responders". Three pediatric radiologists not affiliated with the conduct of the study performed the ratings. Average scores were derived for each patient at each assessment.
3 secondary outcomes
Maximum Serum Concentration of Asfotase Alfa (Cmax)
Time frame: Study Week 1 (0 to 168 hours post-dose). Study Week 2 and Study Week 3 (0 to 48 hours post-dose)
Time at Maximum Serum Concentration of Asfotase Alfa (Tmax)
Time frame: Study Week 1 (0 to 168 hours post-dose). Study Week 2 and Study Week 3 (0 to 48 hours post-dose).
Area Under Serum Concentration-time Curve to Last Measurable Concentration of Asfotase Alfa (AUCt)
Time frame: Study Week 1 (0 to 168 hours post-dose). Study Week 2 and Study Week 3 (0 to 48 hours post-dose).
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Apr 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- 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.
- Derived from this study: PubMed 32762706Padidela 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.
- Derived from this study: PubMed 26529632Whyte 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.
- Derived from this study: PubMed 22397652Whyte MP, Greenberg CR, Salman NJ, Bober MB, McAlister WH, Wenkert D, Van Sickle BJ, Simmons JH, Edgar TS, Bauer ML, Hamdan MA, Bishop N, Lutz RE, McGinn M, Craig S, Moore JN, Taylor JW, Cleveland RH, Cranley WR, Lim R, Thacher TD, Mayhew JE, Downs M, Millan JL, Skrinar AM, Crine P, Landy H. Enzyme-replacement therapy in life-threatening hypophosphatasia. N Engl J Med. 2012 Mar 8;366(10):904-13. doi: 10.1056/NEJMoa1106173.
- 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.
10 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing asfotase alfa in people with Hypophosphatasia (HPP), run by Alexion Pharmaceuticals, Inc. at 10 sites in 4 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 22 inclusion and 7 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 1 Apr 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in United States, United Kingdom, Canada, 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 combined 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.
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 30 Sep 2011). 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?
Change in Rickets Severity From Baseline to Week 24, Based on Assessment of Skeletal Radiographs Using Radiologic Global Impression of Change (RGI-C) (time frame: 24 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 NCT00744042, which also lists 5 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 1 Apr 2019; AzTrials last refreshed its copy on 8 Nov 2026.