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

Study Overview
=================
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.

Official Title
-----------------
An Open-label Extension of Study TKT028 Evaluating Safety and Clinical Outcomes of Replagal® Enzyme Replacement Therapy Administered to Adult Patients With Fabry Disease

Conditions
-----------------
Fabry Disease

Intervention / Treatment
-----------------
* Biological: Replagal


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Replagal 0.2 mg/kg EOW<br>Intravenous, 0.2mg/kg EOW | Biological: Replagal<br>* 0.2 mg/kg administered intravenously [IV] every other week<br>* Other names: DRX005B;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Left Ventricular Mass Indexed to Height (LVMI) |  | Baseline to 12 months | 
| Safety Evaluations |  | Baseline to 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Maximal Oxygen Consumption (VO2max) at Peak Exercise |  | Baseline to 12 months | 
| Change From Baseline in Distance Walked in 6- Minute Walk Test (6MWT) |  | Baseline to 12 months | 
| 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. | Baseline to 12 months | 
| 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. | Baseline to 12 months | 
| Change From Baseline in Plasma Gb3 |  | 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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Agalsidase alfa, Alpha-Galactosidase, Replagal, Enzyme Replacement Therapy