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Extension Study of TKT028 Evaluating Safety and Clinical Outcomes of Replagal® in Adult Patients With Fabry Disease

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ClinicalTrials.gov Identifier: NCT01124643
Recruitment Status : Completed
First Posted : May 17, 2010
Results First Posted : August 22, 2014
Last Update Posted : December 13, 2018
Sponsor:
Information provided by (Responsible Party):
Shire

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Fabry Disease
Intervention Biological: Replagal
Enrollment 35
Recruitment Details  
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.

Arm/Group Title Replagal® (0.2 mg/kg)
Hide Arm/Group Description Replagal 0.2 milligram per kilogram (mg/kg) intravenously (IV), every other week (EOW).
Period Title: Overall Study
Started 35
Completed 34
Not Completed 1
Reason Not Completed
Death             1
Arm/Group Title Replagal® (0.2 mg/kg)
Hide Arm/Group Description Replagal 0.2 mg/kg IV, EOW
Overall Number of Baseline Participants 35
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 35 participants
52.3  (9.86)
Age, Customized   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 35 participants
>=65 years 3
Between 18 and 65 years 32
[1]
Measure Description: Age at time of consent
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 35 participants
Female
16
  45.7%
Male
19
  54.3%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 35 participants
AUSTRALIA 2
CZECH REPUBLIC 5
FINLAND 5
POLAND 13
SLOVENIA 4
UNITED KINGDOM 3
UNITED STATES 3
Left Ventricular Mass Indexed to Height (LVMI)   [1] 
Mean (Standard Deviation)
Unit of measure:  Gram per meter to the power 2.7(g/m^2.7)
Number Analyzed 35 participants
81.18  (32.13)
[1]
Measure Description: Number of participants analyzed for this baseline characteristic was 33
Maximal Oxygen Consumption (VO2max)   [1] 
Mean (Standard Deviation)
Unit of measure:  Milliliter/minute/kilogram (mL/min/kg)
Number Analyzed 35 participants
20.2  (6.73)
[1]
Measure Description: Number of participants analyzed for this baseline characteristic was 32
Distance Walked in 6-Minute Walk Test (6MWT)   [1] 
Mean (Standard Deviation)
Unit of measure:  Meters
Number Analyzed 35 participants
515.5  (144.13)
[1]
Measure Description: Number of participants analyzed for this baseline characteristic was 34
Minnesota Living with Heart Failure Questionnaire (MLHF-Q) Summary Score   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 35 participants
26.5  (26.95)
[1]
Measure Description: 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.
New York Heart Association (NYHA) Functional Class   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 35 participants
Class I (Very Mild) 21
Class II (Mild) 13
Class III (Moderate) 1
Class IV (Severe) 0
[1]
Measure Description: 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
Plasma Gb3 (globotriaosylceramide)  
Mean (Standard Deviation)
Unit of measure:  Nanomoles per milliliter (nmol/mL)
Number Analyzed 35 participants
4.35  (2.51)
Estimated Glomerular Filtration Rate (eGFR)  
Mean (Standard Deviation)
Unit of measure:  (mL/min/1.73m^2)
Number Analyzed 35 participants
77.60  (26.12)
Albumin-to-Creatinine (A/Cr) Ratio   [1] 
Mean (Standard Deviation)
Unit of measure:  Ratio
Number Analyzed 35 participants
284.1  (712.90)
[1]
Measure Description: Number of participants analyzed for this baseline characteristic was 33
1.Primary Outcome
Title Change From Baseline in Left Ventricular Mass Indexed to Height (LVMI)
Hide Description [Not Specified]
Time Frame Baseline to 12 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Replagal® (0.2 mg/kg)
Hide Arm/Group Description:
Replagal 0.2 mg/kg IV, EOW
Overall Number of Participants Analyzed 32
Mean (Standard Deviation)
Unit of Measure: g/m^2.7
-0.75  (13.46)
2.Primary Outcome
Title Safety Evaluations
Hide Description [Not Specified]
Time Frame Baseline to 12 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT population
Arm/Group Title Replagal® (0.2 mg/kg)
Hide Arm/Group Description:
Replagal 0.2 mg/kg IV, EOW
Overall Number of Participants Analyzed 35
Measure Type: Number
Unit of Measure: participants
No Adverse Event (AE) 3
At least one AE 32
At least one study drug-related AE 2
At least one severe or life-threatening AE 5
At least one Serious Adverse Event (SAE) 6
At least one study drug-related SAE 0
Discontinued due to an AE 1
Deaths 1
3.Secondary Outcome
Title Change From Baseline in Maximal Oxygen Consumption (VO2max) at Peak Exercise
Hide Description [Not Specified]
Time Frame Baseline to 12 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT population. Test was not done or test was not valid for all participants.
Arm/Group Title Replagal® (0.2 mg/kg)
Hide Arm/Group Description:
Replagal 0.2 mg/kg IV, EOW
Overall Number of Participants Analyzed 28
Mean (Standard Deviation)
Unit of Measure: (mL/min/kg)
-0.7  (3.11)
4.Secondary Outcome
Title Change From Baseline in Distance Walked in 6- Minute Walk Test (6MWT)
Hide Description [Not Specified]
Time Frame Baseline to 12 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT population. Test was not done or test was not valid for all participants.
Arm/Group Title Replagal® (0.2 mg/kg)
Hide Arm/Group Description:
Replagal 0.2 mg/kg IV, EOW
Overall Number of Participants Analyzed 32
Mean (Standard Deviation)
Unit of Measure: meters
-11.2  (83.99)
5.Secondary Outcome
Title Change From Baseline in the Minnesota Living With Heart Failure Questionnaire (MLHF- Q)
Hide Description 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT population. Number of participants analyzed signifies participants evaluable for this endpoint.
Arm/Group Title Replagal® (0.2 mg/kg)
Hide Arm/Group Description:
Replagal 0.2 mg/kg IV, EOW
Overall Number of Participants Analyzed 34
Mean (Standard Deviation)
Unit of Measure: units on a scale
6.0  (19.31)
6.Secondary Outcome
Title Change From Baseline in New York Heart Association (NYHA) Functional Class
Hide Description

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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT population.
Arm/Group Title Replagal® (0.2 mg/kg)
Hide Arm/Group Description:
Replagal 0.2 mg/kg IV, EOW
Overall Number of Participants Analyzed 35
Measure Type: Number
Unit of Measure: participants
Improved ≥ 1 NYHA Functional Class 0
Maintained NYHA Functional Class 34
Missing 1
7.Secondary Outcome
Title Change From Baseline in Plasma Gb3
Hide Description [Not Specified]
Time Frame Baseline to 12 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT population. Number of participants analyzed signifies participants evaluable for this endpoint.
Arm/Group Title Replagal® (0.2 mg/kg)
Hide Arm/Group Description:
Replagal 0.2 mg/kg IV, EOW
Overall Number of Participants Analyzed 34
Mean (Standard Deviation)
Unit of Measure: (nmol/mL)
-1.18  (1.52)
8.Secondary Outcome
Title Change From Baseline in eGFR
Hide Description [Not Specified]
Time Frame Baseline to 12 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT population. Number of participants analyzed signifies participants evaluable for this endpoint.
Arm/Group Title Replagal® (0.2 mg/kg)
Hide Arm/Group Description:
Replagal 0.2 mg/kg IV, EOW
Overall Number of Participants Analyzed 34
Mean (Standard Deviation)
Unit of Measure: (mL/min/1.73m^2)
-3.25  (10.22)
9.Secondary Outcome
Title Change From Baseline in Albumin/Creatinine (A/Cr) Ratio
Hide Description [Not Specified]
Time Frame Baseline to 12 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT population. Number of participants analyzed signifies participants evaluable for this endpoint.
Arm/Group Title Replagal® (0.2 mg/kg)
Hide Arm/Group Description:
Replagal 0.2 mg/kg IV, EOW
Overall Number of Participants Analyzed 34
Mean (Standard Deviation)
Unit of Measure: Ratio
178.5  (857.74)
Time Frame Baseline to 12 Months
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Replagal® (0.2 mg/kg)
Hide Arm/Group Description Replagal 0.2 mg/kg IV, EOW
All-Cause Mortality
Replagal® (0.2 mg/kg)
Affected / at Risk (%)
Total   --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Replagal® (0.2 mg/kg)
Affected / at Risk (%) # Events
Total   6/35 (17.14%)    
Cardiac disorders   
Acute myocardial infarction * 1  1/35 (2.86%)  1
Atrial fibrillation * 1  2/35 (5.71%)  5
Cardiac failure * 1  1/35 (2.86%)  1
Myocardial infarction * 1  1/35 (2.86%)  1
Congenital, familial and genetic disorders   
Hydrocele * 1  1/35 (2.86%)  1
Gastrointestinal disorders   
Gastritis * 1  1/35 (2.86%)  1
Injury, poisoning and procedural complications   
Arteriovenous fistula site complication * 1  1/35 (2.86%)  2
Arteriovenous fistula site haemorrhage * 1  1/35 (2.86%)  1
Musculoskeletal and connective tissue disorders   
Intervertebral disc disorder * 1  1/35 (2.86%)  1
Nervous system disorders   
Cerebrovascular accident * 1  1/35 (2.86%)  1
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (12)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Replagal® (0.2 mg/kg)
Affected / at Risk (%) # Events
Total   32/35 (91.43%)    
Blood and lymphatic system disorders   
Anaemia * 1  3/35 (8.57%)  3
Iron deficiency anaemia * 1  2/35 (5.71%)  2
Cardiac disorders   
Atrial fibrillation * 1  2/35 (5.71%)  3
Dilatation atrial * 1  2/35 (5.71%)  2
Left atrial dilatation * 1  3/35 (8.57%)  3
Palpitations * 1  5/35 (14.29%)  6
Endocrine disorders   
Hypothyroidism * 1  2/35 (5.71%)  2
Gastrointestinal disorders   
Abdominal pain * 1  2/35 (5.71%)  2
Abdominal pain upper * 1  2/35 (5.71%)  3
Diarrhoea * 1  7/35 (20.00%)  10
Dyspepsia * 1  2/35 (5.71%)  2
Gastrooesophageal reflux disease * 1  2/35 (5.71%)  2
Nausea * 1  5/35 (14.29%)  12
Vomiting * 1  2/35 (5.71%)  7
General disorders   
Chest pain * 1  3/35 (8.57%)  4
Oedema peripheral * 1  4/35 (11.43%)  4
Pyrexia * 1  2/35 (5.71%)  2
Infections and infestations   
Bronchitis * 1  6/35 (17.14%)  7
Nasopharyngitis * 1  10/35 (28.57%)  15
Oral herpes * 1  2/35 (5.71%)  2
Respiratory tract infection * 1  4/35 (11.43%)  4
Urinary tract infection * 1  3/35 (8.57%)  3
Investigations   
Blood glucose increased * 1  2/35 (5.71%)  2
Blood lactate dehydrogenase increased * 1  2/35 (5.71%)  3
Electrocardiogram QT prolonged * 1  3/35 (8.57%)  3
Troponin T increased * 1  2/35 (5.71%)  2
Metabolism and nutrition disorders   
Impaired fasting glucose * 1  2/35 (5.71%)  2
Vitamin D deficiency * 1  2/35 (5.71%)  2
Musculoskeletal and connective tissue disorders   
Arthralgia * 1  4/35 (11.43%)  5
Muscle tightness * 1  2/35 (5.71%)  2
Musculoskeletal pain * 1  3/35 (8.57%)  3
Myalgia * 1  2/35 (5.71%)  3
Pain in extremity * 1  6/35 (17.14%)  7
Nervous system disorders   
Dizziness * 1  6/35 (17.14%)  8
Headache * 1  7/35 (20.00%)  7
Psychiatric disorders   
Disorientation * 1  2/35 (5.71%)  2
Sleep disorder * 1  2/35 (5.71%)  2
Renal and urinary disorders   
Nephrolithiasis * 1  2/35 (5.71%)  2
Respiratory, thoracic and mediastinal disorders   
Cough * 1  5/35 (14.29%)  8
Dyspnoea * 1  3/35 (8.57%)  4
Oropharyngeal pain * 1  2/35 (5.71%)  2
Productive cough * 1  4/35 (11.43%)  4
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (12)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Name/Title: Study Physician
Organization: Shire Development LLC
Phone: +1 866 842 5335
Responsible Party: Shire
ClinicalTrials.gov Identifier: NCT01124643     History of Changes
Other Study ID Numbers: HGT-REP-060
2009-015985-75 ( EudraCT Number )
First Submitted: April 23, 2010
First Posted: May 17, 2010
Results First Submitted: March 25, 2014
Results First Posted: August 22, 2014
Last Update Posted: December 13, 2018