Clinical trial NCT04974749: A Study of REPLAGAL® in Treatment-naive Chinese Participants With Fabry Disease
Official title: An Open-label Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of REPLAGAL® in Treatment-naïve Chinese Subjects With Fabry Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Fabry Disease
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2021-07-23
Enrollment: 20
Sex: ALL
Minimum age (years): 7
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Number of Participants With Serious Treatment-emergent Adverse Events (TEAEs)
timeFrame: From start of study drug administration up to 14 days after end of treatment (EOT) [up to Week 54]
Secondary outcomes:
measure: Number of Participants With TEAEs
timeFrame: From start of study drug administration up to 14 days after EOT (up to Week 54)
measure: Number of Participants With Infusion-related Reactions (IRRs)
timeFrame: From start of study drug administration up to Week 52
measure: Number of Participants With Positive Anti-drug Antibodies (ADA) to REPLAGAL
timeFrame: Baseline up to Week 52
measure: Number of Participants With Positive Neutralizing Antibodies (NAb) to REPLAGAL
timeFrame: Baseline up to Week 52
measure: Number of Participants With Clinically Meaningful Changes in Laboratory Parameters
timeFrame: From start of study drug administration up to Week 52
measure: Number of Participants With Clinically Meaningful Changes in Vital Signs
timeFrame: From start of study drug administration up to Week 52
measure: Number of Participants With Clinically Meaningful Changes in Electrocardiogram (ECG) Parameters
timeFrame: From start of study drug administration up to Week 52
measure: Renal Function as Assessed by Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 52
timeFrame: Baseline, Week 52
measure: Change From Baseline in eGFR Values at Weeks 8, 16, 28, and 40
timeFrame: Baseline, Weeks 8, 16, 28, and 40
measure: Change From Baseline in Left Ventricular Mass Index (LVMI) at Weeks 16 and 52
timeFrame: Baseline, Weeks 16 and 52
measure: Change From Baseline in Left Ventricular Ejection Fraction (LVEF) at Weeks 16 and 52
timeFrame: Baseline, Weeks 16 and 52
measure: Change From Baseline in Urine Protein/Creatinine Ratio
timeFrame: Baseline, Weeks 8, 16, 28, 40, and 52
measure: Change From Baseline in Brief Pain Inventory (BPI) Short Form Pain Severity Total Score
timeFrame: Baseline, Weeks 8, 16, 28, 40, and 52
measure: Change From Baseline in BPI Short Form Pain Interference Total Score
timeFrame: Baseline, Weeks 8, 16, 28, 40, and 52
measure: Percent Change From Baseline in Plasma Globotriaosylsphingosine (Lyso-Gb3) Level
timeFrame: Baseline, Weeks 8, 16, 28, 40, and 52
measure: Number of Participants With Hearing Loss as Assessed by Audiology Testing
timeFrame: Baseline up to Week 52
measure: Area Under Serum Concentration-time Curve From the Time of Dosing to the Last Measurable Concentration (AUC0-last) of REPLAGAL
timeFrame: Pre-infusion (0 minutes), during infusion (20 minutes) and end of infusion (40 minutes), and post-infusion at 50, 60, 90, 120, 240, and 360 minutes at Weeks 0 and 28
measure: Area Under Serum Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of REPLAGAL
timeFrame: Pre-infusion (0 minutes), during infusion (20 minutes) and end of infusion (40 minutes), and post-infusion at 50, 60, 90, 120, 240, and 360 minutes at Weeks 0 and 28
measure: Serum Clearance of Administered Dose (CL) of REPLAGAL
timeFrame: Pre-infusion (0 minutes), during infusion (20 minutes) and end of infusion (40 minutes), and post-infusion at 50, 60, 90, 120, 240, and 360 minutes at Weeks 0 and 28
measure: Serum Clearance of Administered Dose Normalized Based on Body Weight of REPLAGAL
timeFrame: Pre-infusion (0 minutes), during infusion (20 minutes) and end of infusion (40 minutes), and post-infusion at 50, 60, 90, 120, 240, and 360 minutes at Weeks 0 and 28
measure: Maximum Observed Serum Concentration (Cmax) of REPLAGAL
timeFrame: Pre-infusion (0 minutes), during infusion (20 minutes) and end of infusion (40 minutes), and post-infusion at 50, 60, 90, 120, 240, and 360 minutes at Weeks 0 and 28
measure: Terminal Elimination Half-life (T1/2z) of REPLAGAL
timeFrame: Pre-infusion (0 minutes), during infusion (20 minutes) and end of infusion (40 minutes), and post-infusion at 50, 60, 90, 120, 240, and 360 minutes at Weeks 0 and 28
measure: Time to Reach Maximum Observed Serum Concentration (Tmax) of REPLAGAL
timeFrame: Pre-infusion (0 minutes), during infusion (20 minutes) and end of infusion (40 minutes), and post-infusion at 50, 60, 90, 120, 240, and 360 minutes at Weeks 0 and 28
measure: Volume of Distribution at Steady State (Vss) of REPLAGAL
timeFrame: Pre-infusion (0 minutes), during infusion (20 minutes) and end of infusion (40 minutes), and post-infusion at 50, 60, 90, 120, 240, and 360 minutes at Weeks 0 and 28
measure: Volume of Distribution at Steady State Normalized Based on Body Weight of REPLAGAL
timeFrame: Pre-infusion (0 minutes), during infusion (20 minutes) and end of infusion (40 minutes), and post-infusion at 50, 60, 90, 120, 240, and 360 minutes at Weeks 0 and 28
measure: Dose Normalized Area Under Serum Concentration-time Curve From Time Zero to the Last Sampling Time (AUC0-last/Dose) of REPLAGAL
timeFrame: Pre-infusion (0 minutes), during infusion (20 minutes) and end of infusion (40 minutes), and post-infusion at 50, 60, 90, 120, 240, and 360 minutes at Weeks 0 and 28
measure: Dose Normalized Area Under the Serum Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-inf/Dose) of REPLAGAL
timeFrame: Pre-infusion (0 minutes), during infusion (20 minutes) and end of infusion (40 minutes), and post-infusion at 50, 60, 90, 120, 240, and 360 minutes at Weeks 0 and 28
measure: Dose Normalized Maximum Observed Serum Concentration (Cmax/Dose) of REPLAGAL
timeFrame: Pre-infusion (0 minutes), during infusion (20 minutes) and end of infusion (40 minutes), and post-infusion at 50, 60, 90, 120, 240, and 360 minutes at Weeks 0 and 28
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking Union Medical College Hospital
city: Changsha
country: China
facility: Xiangya Hospital, Central South University
city: Chengdu
country: China
facility: West China Hospital, Sichuan University
city: Hangzhou
country: China
facility: The Children's Hospital of Zhejiang University School of Medicine
city: Jinan
country: China
facility: Shandong Provincial Hospital
city: Shanghai
country: China
facility: Ruijin Hospital, Shanghai Jiaotong Uni. School of Med.
Study officials:
affiliation: Takeda
name: Medical Director
role: STUDY_DIRECTOR
References: