Fabry DiseasePhase 2NCT00048906
Alpha-Galactosidase A Replacement Therapy for Fabry Disease
A Phase 2 study testing DRX005B in people with Fabry Disease, run by National Institute of Neurological Disorders and Stroke (NINDS) at 1 site in United States.
Trial summary
This study will determine the safety of the drug Replagal or treating patients with Fabry disease, an inherited metabolic disorder. In this disease, an enzyme called Alpha-galactosidase A, which normally breaks down a fatty substance called globotriaosylceramide (Gb3), is missing or does not function properly. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Fabry Disease
- What is being tested?
- DRX005B
- How many people
- 3 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2002to Nov 2003
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Patient is a male hemizygote, age 18 or above, with evidence of Fabry Disease, defined as Alpha-galactosidase A enzyme deficiency. Alpha-galactosidase A deficiency is defined as a plasma or serum enzyme level less than 1.2 nmoles/hr/mL.
- or
- Patient is a heterozygous carrier female, aged 18 or above, with evidence of Fabry Disease defined as a mutation in the Alpha-galactosidase A gene.
- Patient has clinical evidence of Fabry Disease. For patients with compromised renal function or a history of renal transplant as a result of Fabry Disease, the renal disease must be consistent with Fabry Disease. For other patients, clinical evidence is defined as at least one (1) of the following:
- neurologic disease (neuropathic pain)
- cardiac disease (cadiomyopathy)
Show all 9Show fewer
- cerebrovascular disease (history of stroke)
- dermatologic disease (angiokeratomas)
- gastrointestinal disease (malabsorption and weight loss).
Who cannot join
- Patient is not eligible for an ongoing TKT sponsored placebo-controlled clinical trial that is accruing patients. The selection criteria for ongoing Study TKT010 appear in Appendix D. If another TKT sponsored placebo-controlled clinical trial is initiated during this study, the selection criteria for that study will be appended to this study.
- Patient has a disease other than Fabry that is the cause of the patient's renal dysfunction (for example, diabetes or hypertension).
- Patient has received another investigational therapeutic agent for Fabry Disease.
- Patient has received a renal transplant as a result of renal dysfunction caused by a disease other than Fabry Disease.
- Patient is unable to comply with the protocol, eg, is uncooperative with protocol schedule, refuses to agree to all of the study procedures, is unable to return for safety evaluations, or is otherwise unlikely to complete the study as determined by the investigator or the medical monitor.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institute of Neurological Disorders and Stroke (NINDS)
Bethesda, Maryland, 20892
About this study
Official title: A Safety and Pharmacokinetic Study of Replagal Enzyme Replacement Therapy in Patients With Fabry Disease
This study will determine the safety of the drug Replagal or treating patients with Fabry disease, an inherited metabolic disorder. In this disease, an enzyme called Alpha-galactosidase A, which normally breaks down a fatty substance called globotriaosylceramide (Gb3), is missing or does not function properly. The resulting accumulation of Gb3 causes problems with the kidneys, heart, nerves, and blood vessels. Replagal is a genetically engineered form of Alpha-galactosidase A. Previous studies have shown that patients with Fabry disease who had not progressed to end-stage kidney failure tolerated Replagal replacement therapy well. This study will examine the effects of the drug in patients with kidney problems associated with Fabry disease.
Patients with Fabry disease who are on kidney dialysis, or have had a kidney transplant, may be eligible for this study.
Read more
During this 6 to 12-month study, participants will receive a 40-minute intravenous (IV) infusion of Replagal every other week, with close monitoring during and after the infusions. Before the first infusion, patients will be evaluated with a medical history, physical and neurological examinations, electrocardiogram (ECG), routine blood and urine tests, kidney test, and measurements of height, weight, and vital signs (blood pressure, pulse, breathing rate, temperature). In addition, they will have pharmacokinetic studies immediately before and following the first infusion of Replagal. For these studies, blood samples of less than a teaspoon each will be drawn to measure the level of Replagal enzyme activity. The samples will be collected at the following time points: immediately before the infusion; 20 minutes into the infusion; at the end of the infusion; after the infusion at 50, 60, and 90 minutes, and 2, 3, 4, and 8 hours.
Safety evaluations will be done once a week for the first month and then once a month for the rest of the study period. These evaluations include a physical examination, measurement of vital signs, electrocardiogram, routine blood and urine tests, and kidney testing.
Read the detailed description
The objectives of this clinical trial are to study the effects of a range of renal function on the safety and pharmacokinetics of Replagal enzyme replacement therapy in patients with Fabry Disease. Patients with clinical and genetic or biochemical evidence of Fabry Disease will be selected for this clinical trial. Sixty (60) patients will be enrolled in this clinical trial. Enrollment will be stratified based on baseline renal function as per FDA guidelines. This is an open label clinical study. Baseline evaluations will be conducted over an approximately 3 day period. Patients will receive intravenous (IV) infusions of Replagal at a dose of 0.2 mg/kg/dose every 2 weeks. Pharmacokinetic studies will be performed with the first administered dose. The safety evaluations for patients in this study will include vital signs, physical examinations, adverse event (AE) assessments, electrocardiograms (ECG), and a battery of laboratory tests including measurement of anti-Replagal antibodies. An overview of the study appears in Appendix A.
- Conditions
- Fabry Disease
- Being tested
- DRX005B
- Keywords
- Pharmacokinetics, Enzyme, Lysosomal, Kidney, Stroke, Fabry Disease, Fabrys, Fabry's
- Medical subject headings
- Fabry Disease, Stroke
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DRX005BDrug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Nov 2002 (estimated)
- Study startNov 2002
- Study completionNov 2003
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Fabry DiseaseStudies of the same condition, open and under way.
- More trials run by National Institute of Neurological Disorders and Stroke (NINDS)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
- Enrolment
- 3 participants
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00048906
- Sponsor's protocol ID
- 030043
- Other IDs
- 03-N-0043
- Status last verified
- Nov 2003
- First submitted
- 8 Nov 2002
- Last updated
- 4 Mar 2008
- Results posted
- No
Publications
Brady RO, Gal AE, Bradley RM, Martensson E, Warshaw AL, Laster L. Enzymatic defect in Fabry's disease. Ceramidetrihexosidase deficiency. N Engl J Med. 1967 May 25;276(21):1163-7. doi: 10.1056/NEJM196705252762101. No abstract available.
PubMed 6023233Kahn P. Anderson-Fabry disease: a histopathological study of three cases with observations on the mechanism of production of pain. J Neurol Neurosurg Psychiatry. 1973 Dec;36(6):1053-62. doi: 10.1136/jnnp.36.6.1053.
PubMed 4204059Kaye EM, Kolodny EH, Logigian EL, Ullman MD. Nervous system involvement in Fabry's disease: clinicopathological and biochemical correlation. Ann Neurol. 1988 May;23(5):505-9. doi: 10.1002/ana.410230513.
PubMed 3133979
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Safety and Pharmacokinetic Study of Replagal Enzyme Replacement Therapy in Patients With Fabry Disease
- ClinicalTrials.gov ID
- NCT00048906
- Acronym / sponsor ID
- 030043
- Conditions
- Fabry Disease
- Keywords
- Pharmacokinetics, Enzyme, Lysosomal, Kidney, Stroke, Fabry Disease, Fabrys, Fabry's
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 3 participants
- Lead sponsor
- National Institute of Neurological Disorders and Stroke (NINDS)US National Institutes of Health
- Study start
- Nov 2002
- Study completion
- Nov 2003
- First posted
- 11 Nov 2002 (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 study will determine the safety of the drug Replagal or treating patients with Fabry disease, an inherited metabolic disorder. In this disease, an enzyme called Alpha-galactosidase A, which normally breaks down a fatty substance called globotriaosylceramide (Gb3), is missing or does not function properly. The resulting accumulation of Gb3 causes problems with the kidneys, heart, nerves, and blood vessels. Replagal is a genetically engineered form of Alpha-galactosidase A. Previous studies have shown that patients with Fabry disease who had not progressed to end-stage kidney failure tolerated Replagal replacement therapy well. This study will examine the effects of the drug in patients with kidney problems associated with Fabry disease.
Patients with Fabry disease who are on kidney dialysis, or have had a kidney transplant, may be eligible for this study.
During this 6 to 12-month study, participants will receive a 40-minute intravenous (IV) infusion of Replagal every other week, with close monitoring during and after the infusions. Before the first infusion, patients will be evaluated with a medical history, physical and neurological examinations, electrocardiogram (ECG), routine blood and urine tests, kidney test, and measurements of height, weight, and vital signs (blood pressure, pulse, breathing rate, temperature). In addition, they will have pharmacokinetic studies immediately before and following the first infusion of Replagal. For these studies, blood samples of less than a teaspoon each will be drawn to measure the level of Replagal enzyme activity. The samples will be collected at the following time points: immediately before the infusion; 20 minutes into the infusion; at the end of the infusion; after the infusion at 50, 60, and 90 minutes, and 2, 3, 4, and 8 hours.
Safety evaluations will be done once a week for the first month and then once a month for the rest of the study period. These evaluations include a physical examination, measurement of vital signs, electrocardiogram, routine blood and urine tests, and kidney testing.
Detailed description
The objectives of this clinical trial are to study the effects of a range of renal function on the safety and pharmacokinetics of Replagal enzyme replacement therapy in patients with Fabry Disease. Patients with clinical and genetic or biochemical evidence of Fabry Disease will be selected for this clinical trial. Sixty (60) patients will be enrolled in this clinical trial. Enrollment will be stratified based on baseline renal function as per FDA guidelines. This is an open label clinical study. Baseline evaluations will be conducted over an approximately 3 day period. Patients will receive intravenous (IV) infusions of Replagal at a dose of 0.2 mg/kg/dose every 2 weeks. Pharmacokinetic studies will be performed with the first administered dose. The safety evaluations for patients in this study will include vital signs, physical examinations, adverse event (AE) assessments, electrocardiograms (ECG), and a battery of laboratory tests including measurement of anti-Replagal antibodies. An overview of the study appears in Appendix A.
Study design
- Primary purpose
- Treatment
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (9 listed)
- Patient is a male hemizygote, age 18 or above, with evidence of Fabry Disease, defined as Alpha-galactosidase A enzyme deficiency. Alpha-galactosidase A deficiency is defined as a plasma or serum enzyme level less than 1.2 nmoles/hr/mL.
- or
- Patient is a heterozygous carrier female, aged 18 or above, with evidence of Fabry Disease defined as a mutation in the Alpha-galactosidase A gene.
- Patient has clinical evidence of Fabry Disease. For patients with compromised renal function or a history of renal transplant as a result of Fabry Disease, the renal disease must be consistent with Fabry Disease. For other patients, clinical evidence is defined as at least one (1) of the following:
- neurologic disease (neuropathic pain)
Key exclusion criteria (5 listed)
- Patient is not eligible for an ongoing TKT sponsored placebo-controlled clinical trial that is accruing patients. The selection criteria for ongoing Study TKT010 appear in Appendix D. If another TKT sponsored placebo-controlled clinical trial is initiated during this study, the selection criteria for that study will be appended to this study.
- Patient has a disease other than Fabry that is the cause of the patient's renal dysfunction (for example, diabetes or hypertension).
- Patient has received another investigational therapeutic agent for Fabry Disease.
- Patient has received a renal transplant as a result of renal dysfunction caused by a disease other than Fabry Disease.
- Patient is unable to comply with the protocol, eg, is uncooperative with protocol schedule, refuses to agree to all of the study procedures, is unable to return for safety evaluations, or is otherwise unlikely to complete the study as determined by the investigator or the medical monitor.
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 |
|---|---|---|
| DRX005B | Drug | – |
Primary outcome
Not reported in the source record.
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 4 Mar 2008.
- Background: PubMed 6023233Brady RO, Gal AE, Bradley RM, Martensson E, Warshaw AL, Laster L. Enzymatic defect in Fabry's disease. Ceramidetrihexosidase deficiency. N Engl J Med. 1967 May 25;276(21):1163-7. doi: 10.1056/NEJM196705252762101. No abstract available.
- Background: PubMed 4204059Kahn P. Anderson-Fabry disease: a histopathological study of three cases with observations on the mechanism of production of pain. J Neurol Neurosurg Psychiatry. 1973 Dec;36(6):1053-62. doi: 10.1136/jnnp.36.6.1053.
- Background: PubMed 3133979Kaye EM, Kolodny EH, Logigian EL, Ullman MD. Nervous system involvement in Fabry's disease: clinicopathological and biochemical correlation. Ann Neurol. 1988 May;23(5):505-9. doi: 10.1002/ana.410230513.
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing DRX005B in people with Fabry Disease, run by National Institute of Neurological Disorders and Stroke (NINDS) at 1 site in United States.
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 9 inclusion and 5 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 4 Mar 2008. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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 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 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.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00048906, which also lists 3 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 Mar 2008.