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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00864851




Registration number
NCT00864851
Ethics application status
Date submitted
18/03/2009
Date registered
18/03/2009
Date last updated
23/11/2018

Titles & IDs
Public title
Safety and Efficacy Study of Several Replagal Dosing Regimens on Cardiac Function in Adults With Fabry Disease
Scientific 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
Secondary ID [1] 0 0
2007-005543-22
Secondary ID [2] 0 0
TKT028
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Fabry Disease 0 0
Fabry Disease 0 0
Condition category
Condition code
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Metabolic and Endocrine 0 0 0 0
Metabolic disorders
Metabolic and Endocrine 0 0 0 0
Other metabolic disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - Replagal
Other interventions - Replagal

Active Comparator: Replagal 0.2 mg/kg, IV, every other week - Patients randomized to receive Replagal 0.2 mg/kg via intravenous infusion every other week for 52 weeks.

Active Comparator: Replagal 0.2 mg/kg, IV, weekly - Patients randomized to receive Replagal 0.2 mg/kg via intravenous infusion every week for 52 weeks.

Active Comparator: Replagal 0.4 mg/kg, IV, weekly - Patients randomized to receive Replagal 0.4 mg/kg via intravenous infusion every week for 52 weeks.

Active Comparator: Replagal 0.2 mg/kg, IV, every other week - Patients randomized to receive Replagal 0.2 mg/kg via intravenous infusion every other week for 52 weeks.

Active Comparator: Replagal 0.2 mg/kg, IV, weekly - Patients randomized to receive Replagal 0.2 mg/kg via intravenous infusion every week for 52 weeks.

Active Comparator: Replagal 0.4 mg/kg, IV, weekly - Patients randomized to receive Replagal 0.4 mg/kg via intravenous infusion every week for 52 weeks.


Other interventions: Replagal
Intravenous (IV) infusion for 12 months

Other interventions: Replagal
Intravenous (IV) infusion for 12 months

Intervention code [1] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change From Baseline to Month 12 in Left Ventricular Mass Indexed to Height (LVMI) - Left ventricular mass (LVM) was measured through echocardiography.
Timepoint [1] 0 0
Baseline, Month 12 (Week 53)
Primary outcome [2] 0 0
Change From Baseline to Month 12 in Left Ventricular Mass Indexed to Height (LVMI) - Left ventricular mass (LVM) was measured through echocardiography.
Timepoint [2] 0 0
Baseline, Month 12 (Week 53)
Secondary outcome [1] 0 0
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).
Timepoint [1] 0 0
Baseline, Month 12 (Week 53)
Secondary outcome [2] 0 0
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.
Timepoint [2] 0 0
Baseline, Month 12 (Week 53)
Secondary outcome [3] 0 0
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.
Timepoint [3] 0 0
Baseline, Month 12 (Week 53)
Secondary outcome [4] 0 0
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.
Timepoint [4] 0 0
Baseline, Month 12 (Week 53)
Secondary outcome [5] 0 0
Change From Baseline to Month 12 in Plasma Globotriaosylceramide (GB3)
Timepoint [5] 0 0
Baseline, Month 12 (Week 53)
Secondary outcome [6] 0 0
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.
Timepoint [6] 0 0
Baseline, Month 12 (Week 53)
Secondary outcome [7] 0 0
Change From Baseline to Month 12 in Urinary Albumin/Creatinine (A/Cr) Ratio
Timepoint [7] 0 0
Baseline, Month 12 (Week 53)
Secondary outcome [8] 0 0
Safety Evaluation - Adverse events were collected throughout the study, from the time of informed consent to approximately 30 days post-final infusion.
Timepoint [8] 0 0
56 Weeks
Secondary outcome [9] 0 0
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).
Timepoint [9] 0 0
Baseline, Month 12 (Week 53)
Secondary outcome [10] 0 0
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.
Timepoint [10] 0 0
Baseline, Month 12 (Week 53)
Secondary outcome [11] 0 0
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.
Timepoint [11] 0 0
Baseline, Month 12 (Week 53)
Secondary outcome [12] 0 0
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.
Timepoint [12] 0 0
Baseline, Month 12 (Week 53)
Secondary outcome [13] 0 0
Change From Baseline to Month 12 in Plasma Globotriaosylceramide (GB3)
Timepoint [13] 0 0
Baseline, Month 12 (Week 53)
Secondary outcome [14] 0 0
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.
Timepoint [14] 0 0
Baseline, Month 12 (Week 53)
Secondary outcome [15] 0 0
Change From Baseline to Month 12 in Urinary Albumin/Creatinine (A/Cr) Ratio
Timepoint [15] 0 0
Baseline, Month 12 (Week 53)
Secondary outcome [16] 0 0
Safety Evaluation - Adverse events were collected throughout the study, from the time of informed consent to approximately 30 days post-final infusion.
Timepoint [16] 0 0
56 Weeks

Eligibility
Key inclusion criteria
- >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;
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
The Royal Melbourne Hospital - Parkville
Recruitment postcode(s) [1] 0 0
3052 - Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
Iowa
Country [3] 0 0
United States of America
State/province [3] 0 0
New York
Country [4] 0 0
United States of America
State/province [4] 0 0
Virginia
Country [5] 0 0
Czechia
State/province [5] 0 0
Prague
Country [6] 0 0
Finland
State/province [6] 0 0
Turku
Country [7] 0 0
Paraguay
State/province [7] 0 0
Asuncion
Country [8] 0 0
Poland
State/province [8] 0 0
Krakow
Country [9] 0 0
Poland
State/province [9] 0 0
Warsaw
Country [10] 0 0
Slovenia
State/province [10] 0 0
Slovenj Gradec
Country [11] 0 0
United Kingdom
State/province [11] 0 0
Salford

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Shire
Address
Country

Ethics approval
Ethics application status

Summary
Brief 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.
Trial website
https://clinicaltrials.gov/show/NCT00864851
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Study Director
Address 0 0
Shire
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications