Fabry Disease
Conditions
Keywords
Agalsidase alfa, Alpha-Galactosidase, Replagal, Enzyme Replacement Therapy
Brief summary
This study will evaluate safety and clinical outcomes of treatment with Replagal in adult participants with Fabry disease who have completed Study TKT028 (NCT00864851).
Detailed description
HGT-REP-060 was designed to provide participants who participated in TKT028 an additional 52 weeks of treatment with Replagal at the standard dose of 0.2 milligram per kilogram (mg/kg) every other week (EOW) to assess the effect of continued Replagal therapy on long-term safety and clinical outcomes for this participant population.
Interventions
BIOLOGICALReplagal
0.2 mg/kg administered intravenously \[IV\] every other week
Sponsors
Shire
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Complete all study requirements and assessments for Study TKT028 less than 30 days (+/- 7 days) prior to the first dose in this extension protocol * Voluntarily signed an Institutional Review Board/Independent Ethics Committee- approved informed consent form after all relevant aspects of the study have been explained and discussed. * Has received and tolerated at least 80% of the total planned Replagal infusions in Study TKT028 * Female participants of child-bearing potential must agree to use a medically acceptable method of contraception at all times during the study and must have a negative pregnancy test at the time of study entry and as required throughout participation in study
Exclusion criteria
* Has received treatment with any investigational drug (other than Replagal) or device within 30 days prior to study entry. * Is unable to comply with the protocol, (eg, is unable to return for safety evaluations, or is otherwise unlikely to complete the study), as determined by the Investigator * Has a positive test for hepatitis B surface antigen (HBsAg), hepatitis C(HCV) antibody, or human immunodeficiency virus (HIV) antibody * Is pregnant or lactating * Is morbidly obese, defined as body mass index (BMI) \>39 kg/m2 * Has any safety or medical issues, as assessed by the Investigator, that contraindicate participation in the study (eg, has experienced an adverse reaction to treatment with Replagal or has a known hypersensitivity to any of the components of Replagal
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change From Baseline in Left Ventricular Mass Indexed to Height (LVMI) | Baseline to 12 months |
| Safety Evaluations | Baseline to 12 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Minnesota Living With Heart Failure Questionnaire (MLHF- Q) | Baseline to 12 months | The MLHF-Q contains 21 questions with answers ranging from 0 (no) to 5 (very much). The final score ( 0 to 105) is the sum of the points for the 21 questions. A higher score indicates a worse quality of life. |
| Change From Baseline in New York Heart Association (NYHA) Functional Class | Baseline to 12 months | Class I: No limitation of physical activity. Ordinary physical activity does not cause undue fatigue, palpitation, dyspnea. Class II: Slight limitation of physical activity. Comfortable at rest, but ordinary physical activity results in fatigue, palpitation, or dyspnea. Class III: Marked limitation of physical activity. Comfortable at rest, but less than ordinary activity causes fatigue, palpitation, or dyspnea. Class IV: Unable to carry out any physical activity without discomfort. Symptoms of cardiac insufficiency at rest. If any physical activity is undertaken, discomfort is increased. |
| Change From Baseline in Maximal Oxygen Consumption (VO2max) at Peak Exercise | Baseline to 12 months | — |
| Change From Baseline in eGFR | Baseline to 12 months | — |
| Change From Baseline in Albumin/Creatinine (A/Cr) Ratio | Baseline to 12 months | — |
| Change From Baseline in Plasma Gb3 | Baseline to 12 months | — |
| Change From Baseline in Distance Walked in 6- Minute Walk Test (6MWT) | Baseline to 12 months | — |
Countries
Australia, Czechia, Finland, Poland, Slovenia, United Kingdom, United States
Participant flow
Pre-assignment details
Screening details: Thirty-five of the 40 subjects who completed the parent study (Study TKT028 \[NCT00864851\]) were enrolled in this extension study.
Participants by arm
| Arm | Count |
|---|---|
| Replagal® (0.2 mg/kg) Replagal 0.2 mg/kg IV, EOW | 35 |
| Total | 35 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 1 |
Baseline characteristics
| Characteristic | Replagal® (0.2 mg/kg) |
|---|---|
| Age, Continuous | 52.3 Years STANDARD_DEVIATION 9.86 |
| Age, Customized >=65 years | 3 Participants |
| Age, Customized Between 18 and 65 years | 32 Participants |
| Albumin-to-Creatinine (A/Cr) Ratio | 284.1 Ratio STANDARD_DEVIATION 712.9 |
| Distance Walked in 6-Minute Walk Test (6MWT) | 515.5 meters STANDARD_DEVIATION 144.13 |
| Estimated Glomerular Filtration Rate (eGFR) | 77.60 (mL/min/1.73m^2) STANDARD_DEVIATION 26.12 |
| Left Ventricular Mass Indexed to Height (LVMI) | 81.18 gram per meter to the power 2.7(g/m^2.7) STANDARD_DEVIATION 32.13 |
| Maximal Oxygen Consumption (VO2max) | 20.2 milliliter/minute/kilogram (mL/min/kg) STANDARD_DEVIATION 6.73 |
| Minnesota Living with Heart Failure Questionnaire (MLHF-Q) Summary Score | 26.5 units on a scale STANDARD_DEVIATION 26.95 |
| New York Heart Association (NYHA) Functional Class Class III (Moderate) | 1 Participants |
| New York Heart Association (NYHA) Functional Class Class II (Mild) | 13 Participants |
| New York Heart Association (NYHA) Functional Class Class I (Very Mild) | 21 Participants |
| New York Heart Association (NYHA) Functional Class Class IV (Severe) | 0 Participants |
| Plasma Gb3 (globotriaosylceramide) | 4.35 nanomoles per milliliter (nmol/mL) STANDARD_DEVIATION 2.51 |
| Region of Enrollment AUSTRALIA | 2 Participants |
| Region of Enrollment CZECH REPUBLIC | 5 Participants |
| Region of Enrollment FINLAND | 5 Participants |
| Region of Enrollment POLAND | 13 Participants |
| Region of Enrollment SLOVENIA | 4 Participants |
| Region of Enrollment UNITED KINGDOM | 3 Participants |
| Region of Enrollment UNITED STATES | 3 Participants |
| Sex: Female, Male Female | 16 Participants |
| Sex: Female, Male Male | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 32 / 35 |
| serious Total, serious adverse events | 6 / 35 |
Outcome results
Primary
Change From Baseline in Left Ventricular Mass Indexed to Height (LVMI)
Time frame: Baseline to 12 months
Population: The Intent-to-Treat (ITT) participant population in this study was defined as all participants who provided informed consent and received study drug. Participants who did not have left ventricular hypertrophy were not included in this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Replagal® (0.2 mg/kg) | Change From Baseline in Left Ventricular Mass Indexed to Height (LVMI) | -0.75 g/m^2.7 | Standard Deviation 13.46 |
Primary
Safety Evaluations
Time frame: Baseline to 12 months
Population: ITT population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Replagal® (0.2 mg/kg) | Safety Evaluations | At least one study drug-related AE | 2 participants |
| Replagal® (0.2 mg/kg) | Safety Evaluations | At least one severe or life-threatening AE | 5 participants |
| Replagal® (0.2 mg/kg) | Safety Evaluations | At least one Serious Adverse Event (SAE) | 6 participants |
| Replagal® (0.2 mg/kg) | Safety Evaluations | At least one study drug-related SAE | 0 participants |
| Replagal® (0.2 mg/kg) | Safety Evaluations | Discontinued due to an AE | 1 participants |
| Replagal® (0.2 mg/kg) | Safety Evaluations | Deaths | 1 participants |
| Replagal® (0.2 mg/kg) | Safety Evaluations | No Adverse Event (AE) | 3 participants |
| Replagal® (0.2 mg/kg) | Safety Evaluations | At least one AE | 32 participants |
Secondary
Change From Baseline in Albumin/Creatinine (A/Cr) Ratio
Time frame: Baseline to 12 months
Population: ITT population. Number of participants analyzed signifies participants evaluable for this endpoint.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Replagal® (0.2 mg/kg) | Change From Baseline in Albumin/Creatinine (A/Cr) Ratio | 178.5 Ratio | Standard Deviation 857.74 |
Secondary
Change From Baseline in Distance Walked in 6- Minute Walk Test (6MWT)
Time frame: Baseline to 12 months
Population: ITT population. Test was not done or test was not valid for all participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Replagal® (0.2 mg/kg) | Change From Baseline in Distance Walked in 6- Minute Walk Test (6MWT) | -11.2 meters | Standard Deviation 83.99 |
Secondary
Change From Baseline in eGFR
Time frame: Baseline to 12 months
Population: ITT population. Number of participants analyzed signifies participants evaluable for this endpoint.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Replagal® (0.2 mg/kg) | Change From Baseline in eGFR | -3.25 (mL/min/1.73m^2) | Standard Deviation 10.22 |
Secondary
Change From Baseline in Maximal Oxygen Consumption (VO2max) at Peak Exercise
Time frame: Baseline to 12 months
Population: ITT population. Test was not done or test was not valid for all participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Replagal® (0.2 mg/kg) | Change From Baseline in Maximal Oxygen Consumption (VO2max) at Peak Exercise | -0.7 (mL/min/kg) | Standard Deviation 3.11 |
Secondary
Change From Baseline in New York Heart Association (NYHA) Functional Class
Class I: No limitation of physical activity. Ordinary physical activity does not cause undue fatigue, palpitation, dyspnea. Class II: Slight limitation of physical activity. Comfortable at rest, but ordinary physical activity results in fatigue, palpitation, or dyspnea. Class III: Marked limitation of physical activity. Comfortable at rest, but less than ordinary activity causes fatigue, palpitation, or dyspnea. Class IV: Unable to carry out any physical activity without discomfort. Symptoms of cardiac insufficiency at rest. If any physical activity is undertaken, discomfort is increased.
Time frame: Baseline to 12 months
Population: ITT population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Replagal® (0.2 mg/kg) | Change From Baseline in New York Heart Association (NYHA) Functional Class | Improved ≥ 1 NYHA Functional Class | 0 participants |
| Replagal® (0.2 mg/kg) | Change From Baseline in New York Heart Association (NYHA) Functional Class | Maintained NYHA Functional Class | 34 participants |
| Replagal® (0.2 mg/kg) | Change From Baseline in New York Heart Association (NYHA) Functional Class | Missing | 1 participants |
Secondary
Change From Baseline in Plasma Gb3
Time frame: Baseline to 12 months
Population: ITT population. Number of participants analyzed signifies participants evaluable for this endpoint.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Replagal® (0.2 mg/kg) | Change From Baseline in Plasma Gb3 | -1.18 (nmol/mL) | Standard Deviation 1.52 |
Secondary
Change From Baseline in the Minnesota Living With Heart Failure Questionnaire (MLHF- Q)
The MLHF-Q contains 21 questions with answers ranging from 0 (no) to 5 (very much). The final score ( 0 to 105) is the sum of the points for the 21 questions. A higher score indicates a worse quality of life.
Time frame: Baseline to 12 months
Population: ITT population. Number of participants analyzed signifies participants evaluable for this endpoint.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Replagal® (0.2 mg/kg) | Change From Baseline in the Minnesota Living With Heart Failure Questionnaire (MLHF- Q) | 6.0 units on a scale | Standard Deviation 19.31 |