A Study of REPLAGAL® in Treatment-naive Chinese Participants With Fabry Disease

Study Overview
=================
Brief Summary
-----------------
The main aim of the study is to assess the safety of REPLAGAL. Study participants will receive REPLAGAL as an intravenous infusion every other week for 52 weeks. Participants will visit their study clinic many times throughout the study.

Official Title
-----------------
An Open-label Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of REPLAGAL® in Treatment-naïve Chinese Subjects With Fabry Disease

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

Intervention / Treatment
-----------------
* Biological: REPLAGAL


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Participant and/or legally authorized representative must voluntarily sign an Institutional Review Board/Independent Ethics Committee approved written informed consent form (ICF) after all relevant aspects of the study have been explained and discussed with the participant. For the participants less than (<) 18 years old, participants will give assent AND their parent(s)/legally authorized representative should sign the ICF accordingly. The participant has confirmed diagnosis of Fabry disease as determined by the investigator, according to medical record including: For male participant, Fabry disease is confirmed by a deficiency of α-galactosidase A (GLA) activity and a mutation in the GLA gene For female participant, Fabry disease is confirmed by a mutation in the GLA gene. The participant is 7 to 65 years of age, inclusive, at screening. Female participants of childbearing potential must have a negative pregnancy test at screening. Female participants of childbearing potential must agree to use a medically acceptable method of contraception at all times during the study and for at least 14 days after the final investigational product infusion. The participant is deemed, as determined by the investigator, to have adequate general health to undergo the specified protocol-related procedures and to have no safety or medical contraindications for participation. The participant has not received any treatment (approved or investigational) specific to Fabry disease, such as ERT, chaperone therapy, or substrate reduction therapy. The adult participant (greater than or equal to [>=] 18 years old) must have an estimated glomerular filtration rate (eGFR) of 45 to 120 milliliter per minute per 1.73 meter square (mL/min/1.73 m^2) (inclusive). Serum creatinine is tested and the eGFR is calculated by central laboratory using the Chronic Kidney Disease Epidemiology (CKD-EPI) equation. Exclusion Criteria: In the opinion of the investigator, the participant's life expectancy is less than or equal to (<=) 5 years. The participant has undergone or is scheduled to undergo kidney transplantation or is currently on dialysis or has any signs or symptoms of end stage renal disease. The participant has a urine protein/creatinine ratio of greater than (>) 500 milligram per gram (mg/g). The participant has a clinically relevant history of allergy or signs or symptoms of severe hypersensitivity, which in the investigator's judgment, will substantially increase the participant's risk if he or she participates in the study. In the opinion of the investigator, the participant has non-Fabry disease-related cause of end organ (renal, cardiovascular, central nervous system) dysfunction/failure or is receiving medications that may affect the rate of disease progression, as assessed by renal measures. The participant has a positive test result at screening for hepatitis B surface antigen with detectable hepatitis B viral deoxyribonucleic acid (DNA) load, hepatitis C virus (HCV) antibody with confirmation by HCV ribonucleic acid polymerase chain reaction testing, or human immunodeficiency virus antibody. The participant has received prior treatment with any of the following medications, with the exception of non-systemic use: Chloroquine Amiodarone Monobenzone Gentamicin The participant is pregnant or lactating. The participant has a body mass index >35 kilogram per square meter (kg/m^2). The participant is treated or has been treated with any investigational drug for indication other than Fabry disease within 30 days of study start. The participant and/or the participant's parent(s)/legal guardian is unable to understand the nature, scope, and possible consequences of the study. The participant is unable to comply with the protocol, example, uncooperative with protocol schedule, refusal to agree to all of the study procedures, inability to return for evaluations, or is otherwise unlikely to complete the study, as determined by the investigator.

Ages Eligible for Study
-----------------
Minimum Age: 7 Years
Maximum Age: 65 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<br>Participants will receive REPLAGAL 0.2 milligram per kilogram (mg/kg) body weight, infusion, intravenously every other week (EOW) for 52 weeks. | Biological: REPLAGAL<br>* Participants will receive REPLAGAL infusion intravenously.<br>* Other names: TAK-675;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Serious Treatment-emergent Adverse Events (TEAEs) | An adverse event (AE) is any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this investigational product or medicinal product. Serious AE is any untoward medical occurrence (whether considered to be related to investigational product or not) that at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital abnormality/birth defect, and is an important medical event. A TEAE is defined as any event emerging or manifesting at or after the initiation of treatment with an investigational product or medicinal product or any existing event that worsens in either intensity or frequency following exposure to the investigational product or medicinal product until the end of the safety follow-up period. | From start of study drug administration up to 14 days after end of treatment (EOT) period (up to Week 54) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With TEAEs | An AE is any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this investigational product or medicinal product. A TEAE is defined as any event emerging or manifesting at or after the initiation of treatment with an investigational product or medicinal product or any existing event that worsens in either intensity or frequency following exposure to the investigational product or medicinal product until the end of the safety follow-up period. Number of participants with TEAEs will be reported. | From start of study drug administration up to 14 days after EOT period (up to Week 54) | 
| Number of Participants With Infusion-related Reactions (IRRs) | An IRR will be defined as an event that: occurs within 12 hours after the start of the infusion, begins either during or after the infusion, and is judged as possibly or probably related to treatment with the investigational product. An IRR can be serious or non-serious. Other AEs which occur prior to the infusion, along with AEs associated with protocol-defined testing and assessments (example, laboratory testing and physical examinations), which were performed prior to the infusion, will not be considered as IRRs. Number of participants with IRRs will be reported. | From start of study drug administration up to 14 days after EOT period (up to Week 54) | 
| Number of Participants With Positive Anti-drug Antibody (ADA) to REPLAGAL | Number of participants with positive ADA to REPLAGAL will be reported. | Baseline up to Week 52 | 
| Number of Participants With Positive Neutralizing Antibody (NAb) to REPLAGAL | Number of participants with positive NAb to REPLAGAL will be reported. | Baseline up to Week 52 | 
| Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters | Laboratory assessment will include serum chemistry, hematology, and urinalysis. Number of participants with clinically significant abnormalities in laboratory parameters will be reported. | Baseline up to Week 52 | 
| Number of Participants With Clinically Significant Abnormalities in Vital Signs | Vital sign assessment will include pulse, blood pressure, respiratory rate, and temperature. Number of participants with clinically significant abnormalities in vital signs will be reported. | Baseline up to Week 52 | 
| Number of Participants With Clinically Significant Abnormalities in 12-lead Electrocardiogram (ECG) | ECG parameters will include PR, QRS, QT, QTc intervals, and heart rate. Number of participants with clinically significant abnormalities in 12-lead ECG will be reported. | Baseline up to Week 52 | 
| Change From Baseline in Renal Function at Week 52 | Renal function is assessed by estimated glomerular filtration rate (eGFR) using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula for greater than or equal to (>=) 18 years participants, eGFR = 141 x min (Serum Creatinine [Scr]/κ,1)^(α) x max(Scr/κ,1)^(-1.209) x 0.993^(Age) x 1.018 (if female) x 1.159 (if black) where: Scr is serum creatinine (milligram per deciliter [mg/dL]); κ is 0.7 for females and 0.9 for males; α is -0.329 for females and -0.411 for males; min indicates the minimum of Scr/κ or 1; max indicates the maximum of Scr /κ or 1. For less than (<) 18 years participants, Counahan-Barratt equation will be used for calculation of eGFR. eGFR = (0.43 × height in centimeter [cm])/Scr where, Scr is serum creatinine (mg/dL). Change from baseline in renal function at Week 52 will be reported. | Baseline, Week 52 | 
| Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) Values at Weeks 8, 16, 28 and 40 | The eGFR will be calculated by CKD-EPI formula for >=18 years participants. eGFR = 141 x min (Serum Creatinine [Scr]/κ,1)^(α) x max(Scr/κ,1)^(-1.209) x 0.993^(Age) x 1.018 (if female) x 1.159 (if black) where: Scr is serum creatinine (mg/dL); κ is 0.7 for females and 0.9 for males; α is -0.329 for females and -0.411 for males; min indicates the minimum of Scr/κ or 1; max indicates the maximum of Scr /κ or 1. For <18 years participants, Counahan-Barratt equation will be used for calculation of eGFR. eGFR = (0.43 × height in cm)/Scr where, Scr is serum creatinine (mg/dL). Change from baseline in eGFR values at Weeks 8, 16, 28 and 40 will be reported. | Baseline, Weeks 8, 16, 28 and 40 | 
| Change From Baseline in Left Ventricular Mass Index (LVMI) | Change from baseline in LVMI will be measured by echocardiography at Weeks 16 and 52. | Baseline, Weeks 16 and 52 | 
| Change From Baseline in Left Ventricular Ejection Fraction (LVEF) | Change from baseline in LVEF will be measured by echocardiography at Weeks 16 and 52. | Baseline, Weeks 16 and 52 | 
| Change From Baseline in Urine Protein/Creatinine Ratio at Weeks 8, 16, 28, 40 and 52 | Change from baseline in urine protein/creatinine ratio at Weeks 8, 16, 28, 40 and 52 will be reported. | Baseline, Weeks 8, 16, 28, 40 and 52 | 
| Change From Baseline in Pain as Assessed by Brief Pain Inventory Short Form (BPI-short Form) at Weeks 8, 16, 28, 40 and 52 | BPI-short form is a validated self-report measure to assess the severity of pain and the impact of pain on daily functions. BPI-short form has 4 questions that assess pain intensity (worst, least, average, right now) on 10-point rating scales (0=No pain to 10=Pain as bad as you can imagine) and 7 questions that assess impact of pain on daily functions (general activity, mood, walking ability, normal work, relations with other people, sleep, enjoyment of life) on 10-point rating scales as (0=Does not interfere to 10=Completely interferes). Total score is reported as sum of individual questions score ranging from 0 to 10 with higher numbers indicating worse outcomes. Change from baseline in pain as assessed by BPI-short form at Weeks 8, 16, 28, 40 and 52 will be reported. | Baseline, Weeks 8, 16, 28, 40 and 52 | 
| Change From Baseline in Plasma Globotriaosylsphingosine (Lyso-Gb3) Level at Weeks 8, 16, 28, 40 and 52 | Change from baseline in plasma Lyso-Gb3 levels at Weeks 8, 16, 28, 40 and 52 will be reported. | Baseline, Weeks 8, 16, 28, 40 and 52 | 
| Change From Baseline in Audiology Testing Values | Audiology testing will include pure tone conduction and bone conduction for each ear using 4 different pure tone frequencies (500 hertz [Hz], 1000 Hz, 2000 Hz, and 4000 Hz). Any changes in threshold will be categorized as conductive, sensorineural, or unknown. As planned, only participants <18 years of age will assessed for this outcome measure. Change from baseline in audiology testing values will be reported. | Baseline, Weeks 8, 16, 28, 40 and 52 | 
| Area Under Serum Concentration-time Curve From the Time of Dosing to the Last Measurable concentration (AUC0-last) of REPLAGAL | AUC0-last will be reported. | At Weeks 0 and 28 | 
| Area Under Serum Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of REPLAGAL | AUC0-inf will be reported. | At Weeks 0 and 28 | 
| Serum Clearance of Administered Dose (CL) of REPLAGAL | Clearance is defined as a quantitative measure of the rate at which a drug substance is removed from the body. CL will be reported. | At Weeks 0 and 28 | 
| Serum Clearance of Administered Dose Normalized Based on Body Weight of REPLAGAL | Clearance is defined as a quantitative measure of the rate at which a drug substance is removed from the body. CL will be reported. | At Weeks 0 and 28 | 
| Maximum Observed Serum Concentration (Cmax) of REPLAGAL | Cmax will be reported. | At Weeks 0 and 28 | 
| Terminal Elimination Half-life (T1/2) of REPLAGAL | T1/2 is defined as the natural log of 2 divided by the terminal rate constant (ƛz). T1/2 will be reported. | At Weeks 0 and 28 | 
| Time to Reach Maximum Observed Serum Concentration (Tmax) of REPLAGAL | Tmax will be reported. | At Weeks 0 and 28 | 
| Volume of Distribution at Steady State (Vss) of REPLAGAL | Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired serum concentration of a drug. Vss will be reported. | At Weeks 0 and 28 | 
| Volume of Distribution at Steady State Normalized Based on Body Weight of REPLAGAL | Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired serum concentration of a drug. Vss will be reported. | At Weeks 0 and 28 | 
| Dose Normalized Area Under Serum Concentration-time Curve From Time Zero to the Last Sampling Time (AUClast/Dose) of REPLAGAL | AUClast/Dose will be reported. | At Weeks 0 and 28 | 
| Dose Normalized Area Under the Serum Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-inf/Dose) of REPLAGAL | AUC0-inf/Dose will be reported. | At Weeks 0 and 28 | 
| Dose Normalized Maximum Observed Serum Concentration (Cmax/Dose) of REPLAGAL | Cmax/Dose will be reported. | At Weeks 0 and 28 |