Trial Outcomes & Findings for Extension Study of TKT028 Evaluating Safety and Clinical Outcomes of Replagal® in Adult Patients With Fabry Disease (NCT NCT01124643)
NCT ID: NCT01124643
Last Updated: 2021-06-08
Results Overview
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
35 participants
Primary outcome timeframe
Baseline to 12 months
Results posted on
2021-06-08
Participant Flow
Screening details: Thirty-five of the 40 subjects who completed the parent study (Study TKT028 \[NCT00864851\]) were enrolled in this extension study.
Participant milestones
| Measure |
Replagal® (0.2 mg/kg)
Replagal 0.2 milligram per kilogram (mg/kg) intravenously (IV), every other week (EOW).
|
|---|---|
|
Overall Study
STARTED
|
35
|
|
Overall Study
COMPLETED
|
34
|
|
Overall Study
NOT COMPLETED
|
1
|
Reasons for withdrawal
| Measure |
Replagal® (0.2 mg/kg)
Replagal 0.2 milligram per kilogram (mg/kg) intravenously (IV), every other week (EOW).
|
|---|---|
|
Overall Study
Death
|
1
|
Baseline Characteristics
Extension Study of TKT028 Evaluating Safety and Clinical Outcomes of Replagal® in Adult Patients With Fabry Disease
Baseline characteristics by cohort
| Measure |
Replagal® (0.2 mg/kg)
n=35 Participants
Replagal 0.2 mg/kg IV, EOW
|
|---|---|
|
Age, Continuous
|
52.3 Years
STANDARD_DEVIATION 9.86 • n=5 Participants
|
|
Age, Customized
>=65 years
|
3 Participants
n=5 Participants
|
|
Age, Customized
Between 18 and 65 years
|
32 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
16 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
19 Participants
n=5 Participants
|
|
Region of Enrollment
AUSTRALIA
|
2 Participants
n=5 Participants
|
|
Region of Enrollment
CZECH REPUBLIC
|
5 Participants
n=5 Participants
|
|
Region of Enrollment
FINLAND
|
5 Participants
n=5 Participants
|
|
Region of Enrollment
POLAND
|
13 Participants
n=5 Participants
|
|
Region of Enrollment
SLOVENIA
|
4 Participants
n=5 Participants
|
|
Region of Enrollment
UNITED KINGDOM
|
3 Participants
n=5 Participants
|
|
Region of Enrollment
UNITED STATES
|
3 Participants
n=5 Participants
|
|
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 • n=5 Participants
|
|
Maximal Oxygen Consumption (VO2max)
|
20.2 milliliter/minute/kilogram (mL/min/kg)
STANDARD_DEVIATION 6.73 • n=5 Participants
|
|
Distance Walked in 6-Minute Walk Test (6MWT)
|
515.5 meters
STANDARD_DEVIATION 144.13 • n=5 Participants
|
|
Minnesota Living with Heart Failure Questionnaire (MLHF-Q) Summary Score
|
26.5 units on a scale
STANDARD_DEVIATION 26.95 • n=5 Participants
|
|
New York Heart Association (NYHA) Functional Class
Class I (Very Mild)
|
21 Participants
n=5 Participants
|
|
New York Heart Association (NYHA) Functional Class
Class II (Mild)
|
13 Participants
n=5 Participants
|
|
New York Heart Association (NYHA) Functional Class
Class III (Moderate)
|
1 Participants
n=5 Participants
|
|
New York Heart Association (NYHA) Functional Class
Class IV (Severe)
|
0 Participants
n=5 Participants
|
|
Plasma Gb3 (globotriaosylceramide)
|
4.35 nanomoles per milliliter (nmol/mL)
STANDARD_DEVIATION 2.51 • n=5 Participants
|
|
Estimated Glomerular Filtration Rate (eGFR)
|
77.60 (mL/min/1.73m^2)
STANDARD_DEVIATION 26.12 • n=5 Participants
|
|
Albumin-to-Creatinine (A/Cr) Ratio
|
284.1 Ratio
STANDARD_DEVIATION 712.90 • n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline to 12 monthsPopulation: 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.
Outcome measures
| Measure |
Replagal® (0.2 mg/kg)
n=32 Participants
Replagal 0.2 mg/kg IV, EOW
|
|---|---|
|
Change From Baseline in Left Ventricular Mass Indexed to Height (LVMI)
|
-0.75 g/m^2.7
Standard Deviation 13.46
|
PRIMARY outcome
Timeframe: Baseline to 12 monthsPopulation: ITT population
Outcome measures
| Measure |
Replagal® (0.2 mg/kg)
n=35 Participants
Replagal 0.2 mg/kg IV, EOW
|
|---|---|
|
Safety Evaluations
No Adverse Event (AE)
|
3 participants
|
|
Safety Evaluations
At least one AE
|
32 participants
|
|
Safety Evaluations
At least one study drug-related AE
|
2 participants
|
|
Safety Evaluations
At least one severe or life-threatening AE
|
5 participants
|
|
Safety Evaluations
At least one Serious Adverse Event (SAE)
|
6 participants
|
|
Safety Evaluations
At least one study drug-related SAE
|
0 participants
|
|
Safety Evaluations
Discontinued due to an AE
|
1 participants
|
|
Safety Evaluations
Deaths
|
1 participants
|
SECONDARY outcome
Timeframe: Baseline to 12 monthsPopulation: ITT population. Test was not done or test was not valid for all participants.
Outcome measures
| Measure |
Replagal® (0.2 mg/kg)
n=28 Participants
Replagal 0.2 mg/kg IV, EOW
|
|---|---|
|
Change From Baseline in Maximal Oxygen Consumption (VO2max) at Peak Exercise
|
-0.7 (mL/min/kg)
Standard Deviation 3.11
|
SECONDARY outcome
Timeframe: Baseline to 12 monthsPopulation: ITT population. Test was not done or test was not valid for all participants.
Outcome measures
| Measure |
Replagal® (0.2 mg/kg)
n=32 Participants
Replagal 0.2 mg/kg IV, EOW
|
|---|---|
|
Change From Baseline in Distance Walked in 6- Minute Walk Test (6MWT)
|
-11.2 meters
Standard Deviation 83.99
|
SECONDARY outcome
Timeframe: Baseline to 12 monthsPopulation: ITT population. Number of participants analyzed signifies participants evaluable for this endpoint.
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.
Outcome measures
| Measure |
Replagal® (0.2 mg/kg)
n=34 Participants
Replagal 0.2 mg/kg IV, EOW
|
|---|---|
|
Change From Baseline in the Minnesota Living With Heart Failure Questionnaire (MLHF- Q)
|
6.0 units on a scale
Standard Deviation 19.31
|
SECONDARY outcome
Timeframe: Baseline to 12 monthsPopulation: ITT population.
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.
Outcome measures
| Measure |
Replagal® (0.2 mg/kg)
n=35 Participants
Replagal 0.2 mg/kg IV, EOW
|
|---|---|
|
Change From Baseline in New York Heart Association (NYHA) Functional Class
Improved ≥ 1 NYHA Functional Class
|
0 participants
|
|
Change From Baseline in New York Heart Association (NYHA) Functional Class
Maintained NYHA Functional Class
|
34 participants
|
|
Change From Baseline in New York Heart Association (NYHA) Functional Class
Missing
|
1 participants
|
SECONDARY outcome
Timeframe: Baseline to 12 monthsPopulation: ITT population. Number of participants analyzed signifies participants evaluable for this endpoint.
Outcome measures
| Measure |
Replagal® (0.2 mg/kg)
n=34 Participants
Replagal 0.2 mg/kg IV, EOW
|
|---|---|
|
Change From Baseline in Plasma Gb3
|
-1.18 (nmol/mL)
Standard Deviation 1.52
|
SECONDARY outcome
Timeframe: Baseline to 12 monthsPopulation: ITT population. Number of participants analyzed signifies participants evaluable for this endpoint.
Outcome measures
| Measure |
Replagal® (0.2 mg/kg)
n=34 Participants
Replagal 0.2 mg/kg IV, EOW
|
|---|---|
|
Change From Baseline in eGFR
|
-3.25 (mL/min/1.73m^2)
Standard Deviation 10.22
|
SECONDARY outcome
Timeframe: Baseline to 12 monthsPopulation: ITT population. Number of participants analyzed signifies participants evaluable for this endpoint.
Outcome measures
| Measure |
Replagal® (0.2 mg/kg)
n=34 Participants
Replagal 0.2 mg/kg IV, EOW
|
|---|---|
|
Change From Baseline in Albumin/Creatinine (A/Cr) Ratio
|
178.5 Ratio
Standard Deviation 857.74
|
Adverse Events
Replagal® (0.2 mg/kg)
Serious events: 6 serious events
Other events: 32 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Replagal® (0.2 mg/kg)
n=35 participants at risk
Replagal 0.2 mg/kg IV, EOW
|
|---|---|
|
Cardiac disorders
Acute myocardial infarction
|
2.9%
1/35 • Number of events 1 • Baseline to 12 Months
|
|
Cardiac disorders
Atrial fibrillation
|
5.7%
2/35 • Number of events 5 • Baseline to 12 Months
|
|
Cardiac disorders
Cardiac failure
|
2.9%
1/35 • Number of events 1 • Baseline to 12 Months
|
|
Cardiac disorders
Myocardial infarction
|
2.9%
1/35 • Number of events 1 • Baseline to 12 Months
|
|
Congenital, familial and genetic disorders
Hydrocele
|
2.9%
1/35 • Number of events 1 • Baseline to 12 Months
|
|
Gastrointestinal disorders
Gastritis
|
2.9%
1/35 • Number of events 1 • Baseline to 12 Months
|
|
Injury, poisoning and procedural complications
Arteriovenous fistula site complication
|
2.9%
1/35 • Number of events 2 • Baseline to 12 Months
|
|
Injury, poisoning and procedural complications
Arteriovenous fistula site haemorrhage
|
2.9%
1/35 • Number of events 1 • Baseline to 12 Months
|
|
Musculoskeletal and connective tissue disorders
Intervertebral disc disorder
|
2.9%
1/35 • Number of events 1 • Baseline to 12 Months
|
|
Nervous system disorders
Cerebrovascular accident
|
2.9%
1/35 • Number of events 1 • Baseline to 12 Months
|
Other adverse events
| Measure |
Replagal® (0.2 mg/kg)
n=35 participants at risk
Replagal 0.2 mg/kg IV, EOW
|
|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
20.0%
7/35 • Number of events 10 • Baseline to 12 Months
|
|
Gastrointestinal disorders
Dyspepsia
|
5.7%
2/35 • Number of events 2 • Baseline to 12 Months
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
5.7%
2/35 • Number of events 2 • Baseline to 12 Months
|
|
Gastrointestinal disorders
Nausea
|
14.3%
5/35 • Number of events 12 • Baseline to 12 Months
|
|
Gastrointestinal disorders
Vomiting
|
5.7%
2/35 • Number of events 7 • Baseline to 12 Months
|
|
General disorders
Chest pain
|
8.6%
3/35 • Number of events 4 • Baseline to 12 Months
|
|
General disorders
Oedema peripheral
|
11.4%
4/35 • Number of events 4 • Baseline to 12 Months
|
|
General disorders
Pyrexia
|
5.7%
2/35 • Number of events 2 • Baseline to 12 Months
|
|
Blood and lymphatic system disorders
Anaemia
|
8.6%
3/35 • Number of events 3 • Baseline to 12 Months
|
|
Blood and lymphatic system disorders
Iron deficiency anaemia
|
5.7%
2/35 • Number of events 2 • Baseline to 12 Months
|
|
Cardiac disorders
Atrial fibrillation
|
5.7%
2/35 • Number of events 3 • Baseline to 12 Months
|
|
Cardiac disorders
Dilatation atrial
|
5.7%
2/35 • Number of events 2 • Baseline to 12 Months
|
|
Cardiac disorders
Left atrial dilatation
|
8.6%
3/35 • Number of events 3 • Baseline to 12 Months
|
|
Cardiac disorders
Palpitations
|
14.3%
5/35 • Number of events 6 • Baseline to 12 Months
|
|
Endocrine disorders
Hypothyroidism
|
5.7%
2/35 • Number of events 2 • Baseline to 12 Months
|
|
Gastrointestinal disorders
Abdominal pain
|
5.7%
2/35 • Number of events 2 • Baseline to 12 Months
|
|
Gastrointestinal disorders
Abdominal pain upper
|
5.7%
2/35 • Number of events 3 • Baseline to 12 Months
|
|
Infections and infestations
Bronchitis
|
17.1%
6/35 • Number of events 7 • Baseline to 12 Months
|
|
Infections and infestations
Nasopharyngitis
|
28.6%
10/35 • Number of events 15 • Baseline to 12 Months
|
|
Infections and infestations
Oral herpes
|
5.7%
2/35 • Number of events 2 • Baseline to 12 Months
|
|
Infections and infestations
Respiratory tract infection
|
11.4%
4/35 • Number of events 4 • Baseline to 12 Months
|
|
Infections and infestations
Urinary tract infection
|
8.6%
3/35 • Number of events 3 • Baseline to 12 Months
|
|
Investigations
Blood glucose increased
|
5.7%
2/35 • Number of events 2 • Baseline to 12 Months
|
|
Investigations
Blood lactate dehydrogenase increased
|
5.7%
2/35 • Number of events 3 • Baseline to 12 Months
|
|
Investigations
Electrocardiogram QT prolonged
|
8.6%
3/35 • Number of events 3 • Baseline to 12 Months
|
|
Investigations
Troponin T increased
|
5.7%
2/35 • Number of events 2 • Baseline to 12 Months
|
|
Metabolism and nutrition disorders
Impaired fasting glucose
|
5.7%
2/35 • Number of events 2 • Baseline to 12 Months
|
|
Metabolism and nutrition disorders
Vitamin D deficiency
|
5.7%
2/35 • Number of events 2 • Baseline to 12 Months
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
11.4%
4/35 • Number of events 5 • Baseline to 12 Months
|
|
Musculoskeletal and connective tissue disorders
Muscle tightness
|
5.7%
2/35 • Number of events 2 • Baseline to 12 Months
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
8.6%
3/35 • Number of events 3 • Baseline to 12 Months
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
5.7%
2/35 • Number of events 3 • Baseline to 12 Months
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
17.1%
6/35 • Number of events 7 • Baseline to 12 Months
|
|
Nervous system disorders
Dizziness
|
17.1%
6/35 • Number of events 8 • Baseline to 12 Months
|
|
Nervous system disorders
Headache
|
20.0%
7/35 • Number of events 7 • Baseline to 12 Months
|
|
Psychiatric disorders
Disorientation
|
5.7%
2/35 • Number of events 2 • Baseline to 12 Months
|
|
Psychiatric disorders
Sleep disorder
|
5.7%
2/35 • Number of events 2 • Baseline to 12 Months
|
|
Renal and urinary disorders
Nephrolithiasis
|
5.7%
2/35 • Number of events 2 • Baseline to 12 Months
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
14.3%
5/35 • Number of events 8 • Baseline to 12 Months
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
8.6%
3/35 • Number of events 4 • Baseline to 12 Months
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
5.7%
2/35 • Number of events 2 • Baseline to 12 Months
|
|
Respiratory, thoracic and mediastinal disorders
Productive cough
|
11.4%
4/35 • Number of events 4 • Baseline to 12 Months
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Shire's agreements with investigators vary. All agreements provide Shire the right to embargo communications regarding trial results prior to public release for a period ≤180 days from the time submitted to Shire for review. Shire does not prohibit publication, but can require the removal of confidential information(excluding trial results) and can request postponement of a single-center publication until after disclosure of the trial's multi-center publication.
- Publication restrictions are in place
Restriction type: OTHER