E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Deficiency in the enzyme alfa-galactosidase A |
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E.1.1.2 | Therapeutic area | Body processes [G] - Genetic Phenomena [G05] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10016016 |
E.1.2 | Term | Fabry's disease |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objectives of this study are:
• To evaluate the effect of continued dosing with Replagal (0.2 mg/kg administered intravenously [IV] every other week) 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 patients with Fabry disease who are receiving enzyme replacement therapy (ERT) with Replagal
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E.2.2 | Secondary objectives of the trial |
To evaluate the effect of continued dosing with Replagal (0.2 mg/kg administered IV every other week) following 53 weeks of treatment in Study TKT028 on:
• Exercise tolerance, as measured by maximal oxygen consumption (Vo2max) using the standard exponential exercise protocol (STEEP) and by distance walked in meters (m) using the 6-Minute Walk Test (6MWT)
• The improvement from baseline in disease-specific quality of life (QoL) using the summary score of the Minnesota Living with Heart Failure questionnaire (MLHF-Q)
• Improvement from baseline in New York Heart Association (NYHA) functional class for heart failure symptoms
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Complete all study requirements and assessments for Study TKT028 less than 30 days (± 7 days) prior to the first dose in this extension protocol.
2. 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.
3. Has received and tolerated at least 80% of the total planned Replagal infusions in Study TKT028.
4. Female patients 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 their participation in the study.
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E.4 | Principal exclusion criteria |
1. Has received treatment with any investigational drug (other than Replagal) or device within 30 days prior to study entry.
2. 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.
3. Has a positive test for hepatitis B surface antigen (HBsAg), hepatitis C (HCV) antibody, or human immunodeficiency virus (HIV) antibody.
4. Is pregnant or lactating.
5. Is morbidly obese, defined as body mass index (BMI) >39 kg/m2.
6. 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.
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E.5 End points |
E.5.1 | Primary end point(s) |
Change from baseline to Week 53 in this study in LVM normalized to height (LVM/h) as measured by echocardiography. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
The secondary endpoints of this study are:
• Change from baseline to Week 53 in this study in exercise tolerance, as measured by Vo2max
at peak exercise using the STEEP exercise protocol and by distance walked in meters (m)
using the 6MWT
• Change from baseline to Week 53 in this study in NYHA Class
• Change from baseline to Week 53 in this study in QoL using the MLHF-Q summary score |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 5 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Paraguay |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 5 |
E.8.9.2 | In all countries concerned by the trial days | 0 |