Fabry DiseasePhase 3NCT00864851
Safety and Efficacy Study of Several Replagal Dosing Regimens on Cardiac Function in Adults With Fabry Disease
A Phase 3 study testing Replagal in people with Fabry Disease, run by Shire at 12 sites in 8 countries.
Trial summary
The purpose of this study is to compare the safety and effectiveness of various doses of Replagal in patients with cardiomyopathy due to Fabry disease. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Fabry Disease
- What is being tested?
- Replagal
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 44 participants
- Where
- 12 sitesin 8 countries
- Study dates
- 29 Dec 2008to 5 Jul 2012
- Phase
- Phase 3
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- >18 years-old;
- Male:Fabry disease confirmed by deficiency of alfa galactosidase A activity OR Female:Fabry disease confirmed by a mutation of the alfa galactosidase A gene;
- ERT-naïve;
- LVM/h > 50g/m2.7 for males and >47 g/m2.7 for females;
- Negative pregnancy test at enrollment and contraception use required throughout study for female patients;
- Signed informed consent;
Who cannot join
- Class IV heart failure;
- Clinically significant hypertension;
- Hemodynamically significant valvular stenosis or regurgitation;
- Morbid obesity;
- Known autosomal dominant sarcoplasmic contractile protein gene mutation;
- Treatment with any investigational drug or device within the 30 days;
- Unable to comply with the protocol as determined by the Investigator;
- Positive for hepatitis B, hepatitis C or HIV
Trial locations and contacts
12 sites in 8 countries.
12 sites in 8 countries
United States4 sites
University of Iowa Hospitals and Clinics
Iowa City, Iowa, 52242
New York Unversity School of Medicine
New York, New York, 10016
O & O Alpan, LLC
Springfield, Virginia, 22152
AKDHC Tucson Access Center
Tucson, Arizona, 85719
Poland2 sites
Szpital Uniwersytecki w Krakowie
Krakow, 31-066
Instytut Kardiologii
Warsaw, 04-628
United Kingdom1 site
Salford Royal NHS Foundation Trust
Salford, M6 8HD
About this study
Official title: A Multi-Center, Open-Label, Randomized Study Evaluating the Safety and Efficacy of Three Dosing Regimens of Replagal Enzyme Replacement Therapy in Adult Patients With Fabry Disease
The purpose of this study is to compare the safety and effectiveness of various doses of Replagal in patients with cardiomyopathy due to Fabry disease.
Read the detailed description
Fabry disease is an inherited, metabolic disease caused by mutations in the GALA gene. Patients with Fabry disease accumulate a complex glycosphingolipid named globotriaosylceramide (Gb3) in various tissues and organs. All organs are affected in Fabry disease but the majority of the morbidity and mortality are caused by cardiac, renal and neurological dysfunction. Accumulation of Gb3 in the heart causes hypertrophic cardiomyopathy, valvular abnormalities, arrhythmias and infarctions. Replagal has been shown to reduce Gb3 from key tissues and organs, and stabilize renal function in patients with Fabry disease. Evidence suggests that Replagal reduces left ventricular mass (LVM) and improves midwall fractional shortening (MFS) of the heart. Left ventricular hypertrophy is a major cause of morbidity and mortality in patients with Fabry disease.
This is a study of the safety and effectiveness of 3 dosing regimens of Replagal in adult patients with left ventricular hypertrophy due to Fabry disease.
The primary objective of the study is to compare the effects of 2 dosing regimens of Replagal (0.2 mg/kg IV every other week and 0.2 mg/kg IV weekly) on the reduction of left ventricular mass as measured by echocardiography.
The secondary objectives of this study are to compare the effects of 2 dosing regimens of Replagal (0.2 mg/kg IV every other week and 0.2 mg/kg IV weekly) on each of the following: exercise tolerance; improvement in disease-specific quality of life in heart failure patients; improvement of heart failure symptoms; magnitude of reduction in Gb3; rate of decline in renal function and improvement in the severity of proteinuria/albuminuria; and safety.
An alternative treatment regimen of 0.4 mg/kg Replagal IV weekly will also be explored but without formal comparison to the 0.2 mg/kg regimens. The investigation of the safety and efficacy of the 0.4 mg/kg IV weekly regimen is a secondary objective of this study.
- Conditions
- Fabry Disease
- Being tested
- Replagal
- Medical subject headings
- Fabry Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ReplagalBiological
Also called algasidase alfa
Intravenous (IV) infusion for 12 months
| Study group | Role | What they receive |
|---|---|---|
| Replagal 0.2 mg/kg, IV, every other week | Active comparator | Patients randomized to receive Replagal 0.2 mg/kg via intravenous infusion every other week for 52 weeks. Receives: Biological: Replagal |
| Replagal 0.2 mg/kg, IV, weekly | Active comparator | Patients randomized to receive Replagal 0.2 mg/kg via intravenous infusion every week for 52 weeks. Receives: Biological: Replagal |
| Replagal 0.4 mg/kg, IV, weekly | Active comparator | Patients randomized to receive Replagal 0.4 mg/kg via intravenous infusion every week for 52 weeks. Receives: Biological: Replagal |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline to Month 12 in Left Ventricular Mass Indexed to Height (LVMI)
Left ventricular mass (LVM) was measured through echocardiography.
Measured: Baseline, Month 12 (Week 53)
Secondary outcomes (8)
Change From Baseline to Month 12 in Maximal Oxygen Consumption (VO2 Max) at Peak Exercise
Exercise tolerance as measured by VO2 max at peak exercise using the standard exponential exercise protocol (STEEP).
Measured: Baseline, Month 12 (Week 53)
Change From Baseline to Month 12 in Distance Walked in 6-Minute Walk Test (6MWT)
Exercise tolerance using the 6MWT was measured as the total distance walked in 6 minutes.
Measured: Baseline, Month 12 (Week 53)
Change From Baseline to Month 12 in the Minnesota Living With Heart Failure Questionnaire (MLHF-Q) Summary Score
Quality of life (QoL) was evaluated using the MLHF-Q, version 2. The questionnaire is designed to assess the degree to which heart failure symptoms affect a patient's daily life. The summary score ranges from 0 to 105, with a score of 105 representing the highest adverse impact on a patient's QoL.
Measured: Baseline, Month 12 (Week 53)
Change From Baseline to Month 12 in New York Heart Association (NYHA) Functional Class
The NYHA functional classification system relates symptoms to everyday activities and the patient's quality of life. NYHA Classification - The Stages of Heart Failure: Class I (Mild): No limitation of physical activity. Ordinary physical activity does not cause undue fatigue, palpitation, or dyspnea (shortness of breath). Class II (Mild): Slight limitation of physical activity. Comfortable at rest, but ordinary physical activity results in fatigue, palpitation, or dyspnea. Class III (Moderate): Marked limitation of physical activity. Comfortable at rest, but less than ordinary activity causes fatigue, palpitation, or dyspnea. Class IV (Severe): Unable to carry out any physical activity without discomfort. Symptoms of cardiac insufficiency at rest. If any physical activity is undertaken, discomfort is increased.
Measured: Baseline, Month 12 (Week 53)
Change From Baseline to Month 12 in Plasma Globotriaosylceramide (GB3)
Measured: Baseline, Month 12 (Week 53)
Change From Baseline to Month 12 in Estimated Glomerular Filtration Rate (eGFR)
Renal function was assessed by an evaluation of change from baseline to Month 12 in eGFR as calculated using the Modification of Diet for Renal Disease (MDRD) equation.
Measured: Baseline, Month 12 (Week 53)
Change From Baseline to Month 12 in Urinary Albumin/Creatinine (A/Cr) Ratio
Measured: Baseline, Month 12 (Week 53)
Safety Evaluation
Adverse events were collected throughout the study, from the time of informed consent to approximately 30 days post-final infusion.
Measured: 56 Weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Mar 2009 (estimated)
- Study start29 Dec 2008
- Primary completion1 Jun 2012
- Study completion5 Jul 2012
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 (1)Papers the sponsor has linked to this study.
- Other trials for Fabry DiseaseStudies of the same condition, open and under way.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 44 participants (actual)
Sponsor and investigators
- Lead sponsor
- Shire
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Study Director, Study director, Takeda
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00864851
- Sponsor's protocol ID
- TKT028
- Other IDs
- 2007-005543-22
- Status last verified
- May 2021
- First submitted
- 18 Mar 2009
- Last updated
- 9 Jun 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Malek LA, Chojnowska L, Spiewak M, Klopotowski M, Misko J, Petryka J, Milosz B, Ruzyllo W. Cardiac magnetic resonance imaging in patients with Fabry's disease. Kardiol Pol. 2010 Aug;68(8):929-34.
PubMed 20730727
Study at a glance
From the registry record, last updated by the sponsor on 9 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multi-Center, Open-Label, Randomized Study Evaluating the Safety and Efficacy of Three Dosing Regimens of Replagal Enzyme Replacement Therapy in Adult Patients With Fabry Disease
- ClinicalTrials.gov ID
- NCT00864851
- Acronym / sponsor ID
- TKT028
- Conditions
- Fabry Disease
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 44 participants (actual)
- Lead sponsor
- ShireIndustry (pharma, biotech, devices)
- Study start
- 29 Dec 2008 (actual)
- Primary completion
- 1 Jun 2012 (actual)
- Study completion
- 5 Jul 2012 (actual)
- First posted
- 19 Mar 2009 (estimated)
- Results
- Posted 6 Jun 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to compare the safety and effectiveness of various doses of Replagal in patients with cardiomyopathy due to Fabry disease.
Detailed description
Fabry disease is an inherited, metabolic disease caused by mutations in the GALA gene. Patients with Fabry disease accumulate a complex glycosphingolipid named globotriaosylceramide (Gb3) in various tissues and organs. All organs are affected in Fabry disease but the majority of the morbidity and mortality are caused by cardiac, renal and neurological dysfunction. Accumulation of Gb3 in the heart causes hypertrophic cardiomyopathy, valvular abnormalities, arrhythmias and infarctions. Replagal has been shown to reduce Gb3 from key tissues and organs, and stabilize renal function in patients with Fabry disease. Evidence suggests that Replagal reduces left ventricular mass (LVM) and improves midwall fractional shortening (MFS) of the heart. Left ventricular hypertrophy is a major cause of morbidity and mortality in patients with Fabry disease.
This is a study of the safety and effectiveness of 3 dosing regimens of Replagal in adult patients with left ventricular hypertrophy due to Fabry disease.
The primary objective of the study is to compare the effects of 2 dosing regimens of Replagal (0.2 mg/kg IV every other week and 0.2 mg/kg IV weekly) on the reduction of left ventricular mass as measured by echocardiography.
The secondary objectives of this study are to compare the effects of 2 dosing regimens of Replagal (0.2 mg/kg IV every other week and 0.2 mg/kg IV weekly) on each of the following: exercise tolerance; improvement in disease-specific quality of life in heart failure patients; improvement of heart failure symptoms; magnitude of reduction in Gb3; rate of decline in renal function and improvement in the severity of proteinuria/albuminuria; and safety.
An alternative treatment regimen of 0.4 mg/kg Replagal IV weekly will also be explored but without formal comparison to the 0.2 mg/kg regimens. The investigation of the safety and efficacy of the 0.4 mg/kg IV weekly regimen is a secondary objective of this study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Replagal 0.2 mg/kg, IV, every other week | Active comparator | Biological: ReplagalPatients randomized to receive Replagal 0.2 mg/kg via intravenous infusion every other week for 52 weeks. |
| Replagal 0.2 mg/kg, IV, weekly | Active comparator | Biological: ReplagalPatients randomized to receive Replagal 0.2 mg/kg via intravenous infusion every week for 52 weeks. |
| Replagal 0.4 mg/kg, IV, weekly | Active comparator | Biological: ReplagalPatients randomized to receive Replagal 0.4 mg/kg via intravenous infusion every week for 52 weeks. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- >18 years-old;
- Male:Fabry disease confirmed by deficiency of alfa galactosidase A activity OR Female:Fabry disease confirmed by a mutation of the alfa galactosidase A gene;
- ERT-naïve;
- LVM/h > 50g/m2.7 for males and >47 g/m2.7 for females;
- Negative pregnancy test at enrollment and contraception use required throughout study for female patients;
Key exclusion criteria (8 listed)
- Class IV heart failure;
- Clinically significant hypertension;
- Hemodynamically significant valvular stenosis or regurgitation;
- Morbid obesity;
- Known autosomal dominant sarcoplasmic contractile protein gene mutation;
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 |
|---|---|---|
| ReplagalAlso: algasidase alfaIntravenous (IV) infusion for 12 months | Biological | Replagal 0.2 mg/kg, IV, every other week, Replagal 0.2 mg/kg, IV, weekly, Replagal 0.4 mg/kg, IV, weekly |
Primary outcome
Change From Baseline to Month 12 in Left Ventricular Mass Indexed to Height (LVMI)
Time frame: Baseline, Month 12 (Week 53)
Left ventricular mass (LVM) was measured through echocardiography.
8 secondary outcomes
Change From Baseline to Month 12 in Maximal Oxygen Consumption (VO2 Max) at Peak Exercise
Time frame: Baseline, Month 12 (Week 53)
Change From Baseline to Month 12 in Distance Walked in 6-Minute Walk Test (6MWT)
Time frame: Baseline, Month 12 (Week 53)
Change From Baseline to Month 12 in the Minnesota Living With Heart Failure Questionnaire (MLHF-Q) Summary Score
Time frame: Baseline, Month 12 (Week 53)
Change From Baseline to Month 12 in New York Heart Association (NYHA) Functional Class
Time frame: Baseline, Month 12 (Week 53)
Change From Baseline to Month 12 in Plasma Globotriaosylceramide (GB3)
Time frame: Baseline, Month 12 (Week 53)
Change From Baseline to Month 12 in Estimated Glomerular Filtration Rate (eGFR)
Time frame: Baseline, Month 12 (Week 53)
Change From Baseline to Month 12 in Urinary Albumin/Creatinine (A/Cr) Ratio
Time frame: Baseline, Month 12 (Week 53)
Safety Evaluation
Time frame: 56 Weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jun 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 20730727Malek LA, Chojnowska L, Spiewak M, Klopotowski M, Misko J, Petryka J, Milosz B, Ruzyllo W. Cardiac magnetic resonance imaging in patients with Fabry's disease. Kardiol Pol. 2010 Aug;68(8):929-34.
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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.
Study Director study director
Takeda
12 sites in 8 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Replagal in people with Fabry Disease, run by Shire at 12 sites in 8 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 6 inclusion and 8 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 9 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in United States, Poland, Australia, Czechia, Finland and 3 more countries. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 6 Jun 2014). 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 From Baseline to Month 12 in Left Ventricular Mass Indexed to Height (LVMI) (time frame: Baseline, Month 12 (Week 53)). 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 NCT00864851, which also lists 1 linked publication.
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 9 Jun 2021.