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

• Register: ClinicalTrials.gov
• Last refreshed on: 29 January 2024
• Main ID: NCT04974749
• Date of registration: 21/07/2021
• Prospective Registration: Yes
• Primary sponsor: Takeda
• Public title: A Study of REPLAGAL® in Treatment-naive Chinese Participants With Fabry Disease
• Scientific title: An Open-label Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of REPLAGAL® in Treatment-naïve Chinese Subjects With Fabry Disease
• Date of first enrolment: May 6, 2022
• Target sample size: 20
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/ct2/show/NCT04974749
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 3

Countries of recruitment

China

Contacts

• Name: Study Director
• Affiliation: Takeda

Key inclusion & exclusion 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
a-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.



Age minimum: 7 Years
Age maximum: 65 Years
Gender: All

Health Condition(s) or Problem(s) studied

Fabry Disease

Intervention(s)

Biological: REPLAGAL

Primary Outcome(s)

Number of Participants With Serious Treatment-emergent Adverse Events (TEAEs) [Time Frame: From start of study drug administration up to 14 days after end of treatment (EOT) period (up to Week 54)]

Secondary Outcome(s)

Change From Baseline in Left Ventricular Mass Index (LVMI) [Time Frame: Baseline, Weeks 16 and 52]

Dose Normalized Area Under Serum Concentration-time Curve From Time Zero to the Last Sampling Time (AUClast/Dose) of REPLAGAL [Time Frame: At Weeks 0 and 28]

Number of Participants With Infusion-related Reactions (IRRs) [Time Frame: From start of study drug administration up to 14 days after EOT period (up to Week 54)]

Change From Baseline in Urine Protein/Creatinine Ratio at Weeks 8, 16, 28, 40 and 52 [Time Frame: 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 [Time Frame: Baseline, Weeks 8, 16, 28, 40 and 52]

Dose Normalized Area Under the Serum Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-inf/Dose) of REPLAGAL [Time Frame: At Weeks 0 and 28]

Number of Participants With Positive Anti-drug Antibody (ADA) to REPLAGAL [Time Frame: Baseline up to Week 52]

Serum Clearance of Administered Dose Normalized Based on Body Weight of REPLAGAL [Time Frame: At Weeks 0 and 28]

Dose Normalized Maximum Observed Serum Concentration (Cmax/Dose) of REPLAGAL [Time Frame: At Weeks 0 and 28]

Area Under Serum Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of REPLAGAL [Time Frame: At Weeks 0 and 28]

Number of Participants With Clinically Significant Abnormalities in 12-lead Electrocardiogram (ECG) [Time Frame: Baseline up to Week 52]

Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters [Time Frame: Baseline up to Week 52]

Number of Participants With TEAEs [Time Frame: From start of study drug administration up to 14 days after EOT period (up to Week 54)]

Change From Baseline in Audiology Testing Values [Time Frame: Baseline, Weeks 8, 16, 28, 40 and 52]

Number of Participants With Clinically Significant Abnormalities in Vital Signs [Time Frame: Baseline up to Week 52]

Number of Participants With Positive Neutralizing Antibody (NAb) to REPLAGAL [Time Frame: Baseline up to Week 52]

Terminal Elimination Half-life (T1/2) of REPLAGAL [Time Frame: At Weeks 0 and 28]

Area Under Serum Concentration-time Curve From the Time of Dosing to the Last Measurable concentration (AUC0-last) of REPLAGAL [Time Frame: At Weeks 0 and 28]

Serum Clearance of Administered Dose (CL) of REPLAGAL [Time Frame: At Weeks 0 and 28]

Time to Reach Maximum Observed Serum Concentration (Tmax) of REPLAGAL [Time Frame: At Weeks 0 and 28]

Volume of Distribution at Steady State (Vss) of REPLAGAL [Time Frame: At Weeks 0 and 28]

Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) Values at Weeks 8, 16, 28 and 40 [Time Frame: Baseline, Weeks 8, 16, 28 and 40]

Maximum Observed Serum Concentration (Cmax) of REPLAGAL [Time Frame: At Weeks 0 and 28]

Volume of Distribution at Steady State Normalized Based on Body Weight of REPLAGAL [Time Frame: At Weeks 0 and 28]

Change From Baseline in Left Ventricular Ejection Fraction (LVEF) [Time Frame: Baseline, Weeks 16 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 [Time Frame: Baseline, Weeks 8, 16, 28, 40 and 52]

Change From Baseline in Renal Function at Week 52 [Time Frame: Baseline, Week 52]

Secondary ID(s)

2022-004246-35

TAK-675-3001

Source(s) of Monetary Support

Please refer to primary and secondary sponsors