Phase 3
N=20
A Study of REPLAGAL® in Treatment-naive Chinese Participants With Fabry Disease
Fabry Disease
Bottom Line
View on ClinicalTrials.gov: NCT04974749 ↗Enrolled (actual)
20
Serious AEs
10.0%
Results posted
Oct 2024
Primary outcome: Primary: Number of Participants With Serious Treatment-emergent Adverse Events (TEAEs) — 2 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- REPLAGAL (Biological)
- Age
- Pediatric, Adult, Older Adult · 7+ yrs
- Sex
- All
- Sponsor
- Takeda
- Primary completion
- Jan 2024
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Serious Treatment-emergent Adverse Events (TEAEs) |
2 | — |
| SECONDARY Number of Participants With TEAEs |
20 | — |
| SECONDARY Number of Participants With Infusion-related Reactions (IRRs) |
5 | — |
| SECONDARY Number of Participants With Positive Anti-drug Antibodies (ADA) to REPLAGAL |
6 | — |
| SECONDARY Number of Participants With Positive Neutralizing Antibodies (NAb) to REPLAGAL |
5 | — |
| SECONDARY Number of Participants With Clinically Meaningful Changes in Laboratory Parameters |
— | — |
| SECONDARY Number of Participants With Clinically Meaningful Changes in Vital Signs |
— | — |
| SECONDARY Number of Participants With Clinically Meaningful Changes in Electrocardiogram (ECG) Parameters |
— | — |
| SECONDARY Renal Function as Assessed by Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 52 |
4.1 | — |
| SECONDARY Change From Baseline in eGFR Values at Weeks 8, 16, 28, and 40 |
-1.2; -0.4; 5.1; 0.3 | — |
| SECONDARY Change From Baseline in Left Ventricular Mass Index (LVMI) at Weeks 16 and 52 |
-0.4696; -1.7261 | — |
| SECONDARY Change From Baseline in Left Ventricular Ejection Fraction (LVEF) at Weeks 16 and 52 |
-1.1; 0.8 | — |
| SECONDARY Change From Baseline in Urine Protein/Creatinine Ratio |
0.0759; 0.1061; 0.0711; 0.0830; 0.0627 | — |
| SECONDARY Change From Baseline in Brief Pain Inventory (BPI) Short Form Pain Severity Total Score |
-1.607; -2.214; -1.833; -1.375; -0.958 | — |
| SECONDARY Change From Baseline in BPI Short Form Pain Interference Total Score |
-2.286; -3.571; -4.738; -3.810; -3.643 | — |
| SECONDARY Percent Change From Baseline in Plasma Globotriaosylsphingosine (Lyso-Gb3) Level |
-36.236; -38.147; -37.764; -35.565; -37.072 | — |
| SECONDARY Number of Participants With Hearing Loss as Assessed by Audiology Testing |
— | — |
| SECONDARY Area Under Serum Concentration-time Curve From the Time of Dosing to the Last Measurable Concentration (AUC0-last) of REPLAGAL |
229000; 297300 | — |
| SECONDARY Area Under Serum Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of REPLAGAL |
233700; 309500 | — |
| SECONDARY Serum Clearance of Administered Dose (CL) of REPLAGAL |
187.4; 195.5 | — |
| SECONDARY Serum Clearance of Administered Dose Normalized Based on Body Weight of REPLAGAL |
3.234; 3.183 | — |
| SECONDARY Maximum Observed Serum Concentration (Cmax) of REPLAGAL |
4620.55; 4507.99 | — |
| SECONDARY Terminal Elimination Half-life (T1/2z) of REPLAGAL |
45.36; 66.34 | — |
| SECONDARY Time to Reach Maximum Observed Serum Concentration (Tmax) of REPLAGAL |
40.000; 40.000 | — |
| SECONDARY Volume of Distribution at Steady State (Vss) of REPLAGAL |
7834; 12310 | — |
| SECONDARY Volume of Distribution at Steady State Normalized Based on Body Weight of REPLAGAL |
135.9; 202.1 | — |
| SECONDARY Dose Normalized Area Under Serum Concentration-time Curve From Time Zero to the Last Sampling Time (AUC0-last/Dose) of REPLAGAL |
0.005411; 0.008119 | — |
| SECONDARY Dose Normalized Area Under the Serum Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-inf/Dose) of REPLAGAL |
0.005520; 0.008489 | — |
| SECONDARY Dose Normalized Maximum Observed Serum Concentration (Cmax/Dose) of REPLAGAL |
0.0001092; 0.0001197 | — |
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) 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 ( ) 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.
Data sourced from ClinicalTrials.gov (NCT04974749). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.