Clinical Trial Results:
An Open-label Extension of Study TKT028 Evaluating Safety and Clinical Outcomes of Replagal® Enzyme Replacement Therapy Administered to Adult Patients with Fabry Disease
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Summary
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EudraCT number |
2009-015985-75 |
Trial protocol |
PL CZ GB FI SI |
Global end of trial date |
08 Jul 2013
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Results information
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Results version number |
v1(current) |
This version publication date |
04 Sep 2018
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First version publication date |
07 Jan 2015
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
HGT-REP-060
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01124643 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Shire Human Genetic Therapies
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Sponsor organisation address |
300 Shire Way, Lexington, MA 02421, United States,
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Public contact |
Medical Monitor, Shire Human Genetic Therapies, +1 781482-9287, ecrombez@shire.com
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Scientific contact |
Medical Monitor, Shire Human Genetic Therapies, +1 781482-9287, ecrombez@shire.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
08 Jul 2013
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
08 Jul 2013
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
• To evaluate the effect of continued dosing with Replagal (0.2 milligram/kilogram [mg/kg] administered intravenously [IV] every other week [EOW]) following 53 weeks of treatment in Study TKT028 (at 0.2 mg/kg IV every other week or 0.2 mg/kg or 0.4 mg/kg IV every week) on the reduction from baseline in left ventricular mass (LVM) as measured by echocardiography
• To collect long-term safety and clinical outcome data in adult subjects with Fabry disease who are receiving enzyme replacement therapy (ERT) with Replagal
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Protection of trial subjects |
The procedures pertaining to the conduct, evaluation, and documentation of this study, were designed to ensure that the Sponsor and Investigators abided by Good Clinical Practice (GCP) as described in the 21 Code of Federal Regulations (CFR) Parts 50, 54, 56, and 312 and the International Conference on Harmonisation (ICH) GCP Guidelines. Compliance with these regulations and guidelines also constitutes compliance with the ethical principles described in the Declaration of Helsinki.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
13 Apr 2010
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Poland: 13
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Country: Number of subjects enrolled |
Slovenia: 4
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Country: Number of subjects enrolled |
United Kingdom: 3
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Country: Number of subjects enrolled |
Czech Republic: 5
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Country: Number of subjects enrolled |
Finland: 5
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Country: Number of subjects enrolled |
Australia: 2
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Country: Number of subjects enrolled |
United States: 3
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Worldwide total number of subjects |
35
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EEA total number of subjects |
30
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
32
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From 65 to 84 years |
3
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85 years and over |
0
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Recruitment
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Recruitment details |
- | ||||||||||
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Pre-assignment
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Screening details |
Thirty-five of the 40 subjects who completed the parent study (Study TKT028) were enrolled in this extension study. | ||||||||||
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Period 1
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Period 1 title |
Replagal® 0.2 mg/kg (overall period)
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Is this the baseline period? |
Yes | ||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||
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Arms
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Arm title
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Replagal® 0.2 mg/kg | ||||||||||
Arm description |
Replagal® 0.2 mg/kg IV, EOW | ||||||||||
Arm type |
Experimental | ||||||||||
Investigational medicinal product name |
Replagal®
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Investigational medicinal product code |
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Other name |
Agalsidase alfa, DRX005B
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Pharmaceutical forms |
Infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Replagal 0.2 mg/kg IV, EOW
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Baseline characteristics reporting groups
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Reporting group title |
Replagal® 0.2 mg/kg
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Reporting group description |
Replagal 0.2 mg/kg IV, EOW | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Replagal® 0.2 mg/kg
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Reporting group description |
Replagal® 0.2 mg/kg IV, EOW | ||
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End point title |
Change From Baseline in Left Ventricular Mass Indexed to Height (LVMI) [1] | ||||||||
End point description |
The Intent-to-Treat (ITT) subject population in this study was defined as all subjects who provided informed consent and received study drug. Subjects who did not have left ventricular hypertrophy were not included in this analysis.
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End point type |
Primary
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End point timeframe |
Baseline to 12 months
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis was performed. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Safety Evaluations [2] | ||||||||||||||||||||||
End point description |
ITT Population was analysed
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End point type |
Primary
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End point timeframe |
Baseline to 12 months
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| Notes [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis was performed. |
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| No statistical analyses for this end point | |||||||||||||||||||||||
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End point title |
Change From Baseline in Maximal Oxygen Consumption (VO2max) at Peak Exercise | ||||||||
End point description |
ITT population was analysed. Test was not done or test was not valid for all subjects.
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End point type |
Secondary
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End point timeframe |
Baseline to 12 months
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| No statistical analyses for this end point | |||||||||
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End point title |
Change From Baseline in Distance Walked in 6- Minute Walk Test (6MWT) | ||||||||
End point description |
ITT population was analysed. Test was not done or test was not valid for all subjects.
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End point type |
Secondary
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End point timeframe |
Baseline to 12 months
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| No statistical analyses for this end point | |||||||||
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End point title |
Change From Baseline in the Minnesota Living With Heart Failure Questionnaire (MLHF- Q) | ||||||||
End point 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.
ITT population was analysed. Number of subjects analysed signifies subjects evaluable for this endpoint.
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End point type |
Secondary
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End point timeframe |
Baseline to 12 months
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| No statistical analyses for this end point | |||||||||
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End point title |
Change From Baseline in New York Heart Association (NYHA) Functional Class | ||||||||||||
End point 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.
ITT population was analysed.
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End point type |
Secondary
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End point timeframe |
Baseline to 12 months
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Change From Baseline in Plasma Gb3 | ||||||||
End point description |
ITT population was analysed. Number of subjects analysed signifies subjects evaluable for this endpoint.
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End point type |
Secondary
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End point timeframe |
Baseline to 12 months
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| No statistical analyses for this end point | |||||||||
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End point title |
Change From Baseline in eGFR | ||||||||
End point description |
ITT population was analysed. Number of subjects analysed signifies subjects evaluable for this endpoint.
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End point type |
Secondary
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End point timeframe |
Baseline to 12 months
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| No statistical analyses for this end point | |||||||||
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End point title |
Change From Baseline in Albumin/Creatinine (A/Cr) Ratio | ||||||||
End point description |
ITT population was analysed. Number of subjects analysed signifies subjects evaluable for this endpoint.
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End point type |
Secondary
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End point timeframe |
Baseline to 12 months
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| No statistical analyses for this end point | |||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Baseline to 12 Months
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Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
12
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Reporting groups
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Reporting group title |
Replagal® 0.2mg/kg
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Reporting group description |
Replagal 0.2 mg/kg IV, EOW | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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16 Oct 2012 |
The following is a list of the major changes that were included in the amendment:
• A secondary baseline from Week 1 from TKT028 could have been utilized for long-term safety and efficacy analyses. For this long-term analysis, the assumption was that there would be no delay in treatment between study TKT028 and HGT-REP-060. However, this second baseline analysis was not performed because 13 of the 35 enrolled subjects (37%) had a delay of at least 37 days between studies and, of these 13 subjects, 7 (20%) had a delay of at least 90 days.
• Clarification was made that weight was to be recorded at the time points defined in the Schedule of Study Procedures, but that Replagal dose was to be calculated based on the subject's weight determined at Week 1 of HGT-REP-060. This dose was to remain fixed throughout the study.
• Antibody testing for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV), and human immunodeficiency virus (HIV) was permitted at the end of the TKT028 study (Week 52), after subject consent, allowing results to be received in time for HGT-REP-060 Week 1 confirmation of study entry criteria.
• The window following possible or probable AEs was expanded to include the time until the event resolved or stabilized or an outcome was reached (whichever came first).
• A definition of infusion related AEs was added as follows:
- An infusion-related adverse event (IRAE) was defined as an AE that 1) occurred within 24 hours after the start of the infusion 2) began either during or after the infusion, and 3) was judged as possibly or probably related to study drug. Other AEs which occurred prior to the infusion, along with AEs associated with protocol-defined testing and assessments (eg, laboratory testing, electrocardiograms (ECGs), and physical examinations) which were performed prior to the infusion, were not defined as IRAEs.
• The category of definitely related AEs was removed. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
