HypophosphatasiaPhase 2NCT00894075
Safety and Efficacy Study of ENB-0040 in Juvenile Patients With Hypophosphatasia (HPP)
A Phase 2 study testing ENB-0040 in people with Hypophosphatasia, run by Alexion Pharmaceuticals, Inc..
Trial 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. Read more about this study
- Who is it for?
- Ages 5 to 12 years
- Conditions the study is for
- Hypophosphatasia
- What is being tested?
- ENB-0040
- Type of treatment
- Injection or infusion
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Jul 2009to Dec 2014
- Phase
- Phase 2
- 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 5 to 12 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Written informed consent from parent or legal guardian prior to participation
- Boys >/= 5 and < 12 years of age and girls >/= 5 and < 10 years of age with open growth plates at time of enrollment
- Documented history of HPP, as evidenced by:
- Presence of HPP-related rickets on skeletal radiographs
- Serum alkaline phosphatase (ALP) below age-adjusted normal range
- Plasma PLP at least twice the upper limit of normal (>/=220 nM)
- Ambulatory without the use of assistive devices
- Ability of patient and parent/guardian to comply with study requirements
Who cannot join
- Serum calcium or phosphorus below age-adjusted normal range
- History of sensitivity to any study drug constituent
- 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
- Treatment with an investigational drug within 1 month before start of study drug
- Current enrollment in any other study involving an investigational new drug, device, or treatment for HPP (eg, bone marrow transplantation)
- Current evidence of a treatable form of rickets
Show all 9Show fewer
- Prior treatment with bisphosphonates
- Bone fracture or orthopedic surgery within the past 12 months
- Major congenital abnormality other than those associated with HPP
About this study
Official title: Single-Center, Case-Control Study of Safety, Efficacy and Pharmacokinetics of ENB-0040 (Human Recombinant Tissue Nonspecific Alkaline Phosphatase Fusion Protein) for Treatment of Hypophosphatasia in Children
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 of the study drug called ENB-0040 and see what effects is has on human juveniles and HPP.
Read the detailed description
Hypophosphatasia (HPP) is a rare inherited form of rickets and osteomalacia caused by inactivating mutations in the gene encoding the tissue-nonspecific isoenzyme of alkaline phosphatase (TNSALP). The prevalence of the disease is thought to be about 1:100,000 although it is markedly higher in a small Canadian Mennonite population (Fraser 1957, Chodirker 1990). Inheritance can be autosomal recessive or dominant, and penetrance is variable resulting in a wide range of clinical expressivity. HPP differs from other forms of rickets and osteomalacia in that serum levels of calcium and phosphorus are generally normal or even elevated (Whyte 2002). Low circulating levels of alkaline phosphatase with elevated serum or urine levels of the TNSALP substrates inorganic pyrophosphate (PPi), pyridoxal 5'-phosphate (PLP) and phosphoethanolamine (PEA) are the biochemical hallmarks of this inborn error of metabolism.
Disease severity in HPP is inversely related to the age at symptom presentation. The most severe cases occur in utero and almost invariably result in death, generally due to pulmonary compromise. Infants who present in the first six months of life have about 50% mortality. Children and adults have less severe disease but can have frequent fractures, bone pain, bowing of the long bones and muscle weakness, and morbidity is generally cumulative. Some patients cannot ambulate independently and end up wheelchair-bound.
- Conditions
- Hypophosphatasia
- Being tested
- ENB-0040
- Keywords
- genetic metabolic disorder, alkaline phosphatase, tissue non-specific alkaline phosphatase, rickets, osteomalacia
- Medical subject headings
- Hypophosphatasia, Rickets, Osteomalacia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ENB-0040Biological
Also called Human Recombinant Tissue Nonspecific Alkaline Phosphatase Fusion Protein, sALP-Fc-D10
1mg/kg subcutaneous injection thrice weekly for 6 months
What is being measured
The primary outcome is the main question the study is designed to answer.
Skeletal radiographs using a qualitative Clinical Global Impression of Change (CGI-C) scoring system
Measured: 6 months
Secondary outcomes (1)
PK using serum peak and trough levels and PD of plasma inorganic pyrophosphate (PPi) and plasma pyridoxal-5' phosphate (PLP) as biomarkers for HPP.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 May 2009 (estimated)
- Study startJul 2009
- Primary completionDec 2014 (estimated)
- Study completionDec 2014 (estimated)
Why it stopped: Withdrawn pending further review of clinical design.
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 HypophosphatasiaStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Alexion Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Michael P. Whyte, MD, Principal investigator, Shriners Hospital, St. Louis. MO
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00894075
- Sponsor's protocol ID
- ENB-004-09
- Status last verified
- Aug 2023
- First submitted
- 4 May 2009
- Last updated
- 4 Aug 2023
- 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 4 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Single-Center, Case-Control Study of Safety, Efficacy and Pharmacokinetics of ENB-0040 (Human Recombinant Tissue Nonspecific Alkaline Phosphatase Fusion Protein) for Treatment of Hypophosphatasia in Children
- ClinicalTrials.gov ID
- NCT00894075
- Acronym / sponsor ID
- ENB-004-09
- Conditions
- Hypophosphatasia
- Keywords
- genetic metabolic disorder, alkaline phosphatase, tissue non-specific alkaline phosphatase, rickets, osteomalacia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Withdrawn pending further review of clinical design.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Alexion Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- Jul 2009
- Primary completion
- Dec 2014 (estimated)
- Study completion
- Dec 2014 (estimated)
- First posted
- 6 May 2009 (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 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 of the study drug called ENB-0040 and see what effects is has on human juveniles and HPP.
Detailed description
Hypophosphatasia (HPP) is a rare inherited form of rickets and osteomalacia caused by inactivating mutations in the gene encoding the tissue-nonspecific isoenzyme of alkaline phosphatase (TNSALP). The prevalence of the disease is thought to be about 1:100,000 although it is markedly higher in a small Canadian Mennonite population (Fraser 1957, Chodirker 1990). Inheritance can be autosomal recessive or dominant, and penetrance is variable resulting in a wide range of clinical expressivity. HPP differs from other forms of rickets and osteomalacia in that serum levels of calcium and phosphorus are generally normal or even elevated (Whyte 2002). Low circulating levels of alkaline phosphatase with elevated serum or urine levels of the TNSALP substrates inorganic pyrophosphate (PPi), pyridoxal 5'-phosphate (PLP) and phosphoethanolamine (PEA) are the biochemical hallmarks of this inborn error of metabolism.
Disease severity in HPP is inversely related to the age at symptom presentation. The most severe cases occur in utero and almost invariably result in death, generally due to pulmonary compromise. Infants who present in the first six months of life have about 50% mortality. Children and adults have less severe disease but can have frequent fractures, bone pain, bowing of the long bones and muscle weakness, and morbidity is generally cumulative. Some patients cannot ambulate independently and end up wheelchair-bound.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 5 to 12 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (8 listed)
- Written informed consent from parent or legal guardian prior to participation
- Boys >/= 5 and < 12 years of age and girls >/= 5 and < 10 years of age with open growth plates at time of enrollment
- Documented history of HPP, as evidenced by:
- Ambulatory without the use of assistive devices
- Ability of patient and parent/guardian to comply with study requirements
Key exclusion criteria (9 listed)
- Serum calcium or phosphorus below age-adjusted normal range
- History of sensitivity to any study drug constituent
- 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
- Treatment with an investigational drug within 1 month before start of study drug
- Current enrollment in any other study involving an investigational new drug, device, or treatment for HPP (eg, bone marrow transplantation)
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 |
|---|---|---|
| ENB-0040Also: Human Recombinant Tissue Nonspecific Alkaline Phosphatase Fusion Protein, sALP-Fc-D101mg/kg subcutaneous injection thrice weekly for 6 months | Biological | – |
Primary outcome
Skeletal radiographs using a qualitative Clinical Global Impression of Change (CGI-C) scoring system
Time frame: 6 months
1 secondary outcome
PK using serum peak and trough levels and PD of plasma inorganic pyrophosphate (PPi) and plasma pyridoxal-5' phosphate (PLP) as biomarkers for HPP.
Time frame: 6 months
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Aug 2023.
- 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.
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Hypophosphatasia
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.
Michael P. Whyte, MD principal investigator
Shriners Hospital, St. Louis. MO
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing ENB-0040 in people with Hypophosphatasia, run by Alexion Pharmaceuticals, Inc..
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 8 inclusion and 9 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: withdrawn, as of the sponsor's last update on 4 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.
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 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?
The study was withdrawn before enrolling participants, so there are no results.
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?
Skeletal radiographs using a qualitative Clinical Global Impression of Change (CGI-C) scoring system (time frame: 6 months). 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 NCT00894075, 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 4 Aug 2023.