Fabry Disease
Conditions
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.
Interventions
BIOLOGICALREPLAGAL
REPLAGAL IV infusion.
Sponsors
Takeda
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
7 Years to 65 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Serious Treatment-emergent Adverse Events (TEAEs) | From start of study drug administration up to 14 days after end of treatment (EOT) [up to Week 54] | An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and that did not necessarily have a causal relationship with this investigational product (IP) or medicinal product. Serious AE was any untoward medical occurrence (whether considered to be related to investigational product or not) that at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital abnormality/birth defect, and was an important medical event. A TEAE was defined as any event emerging at or after the initiation of treatment with an IP or any existing event that worsened in either intensity or frequency following exposure to the IP until the end of the safety follow-up period. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Infusion-related Reactions (IRRs) | From start of study drug administration up to Week 52 | An IRR was defined as an event that began either during or within 24 hours after the start of the infusion, and was judged as related to treatment with the IP. An IRR could be serious or non-serious. Adverse events that were considered IRRs were noted as such in the participant's source documentation. Other AEs which occurred 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, were not considered as IRRs. |
| Number of Participants With Positive Anti-drug Antibodies (ADA) to REPLAGAL | Baseline up to Week 52 | Number of participants with positive ADA to REPLAGAL were reported. |
| Number of Participants With Positive Neutralizing Antibodies (NAb) to REPLAGAL | Baseline up to Week 52 | Number of participants with positive NAb to REPLAGAL were reported. |
| Number of Participants With Clinically Meaningful Changes in Laboratory Parameters | From start of study drug administration up to Week 52 | Laboratory assessment included parameters of serum chemistry, hematology, and urinalysis. Clinically meaningful laboratory parameters assessment was based on investigator interpretation. Number of participants with clinically meaningful changes in laboratory parameters were reported. |
| Number of Participants With Clinically Meaningful Changes in Vital Signs | From start of study drug administration up to Week 52 | Vital sign assessment included pulse, blood pressure, respiratory rate, and temperature. Clinically meaningful vital signs assessment was based on investigator interpretation. Number of participants with clinically meaningful abnormalities in vital signs were reported. |
| Number of Participants With Clinically Meaningful Changes in Electrocardiogram (ECG) Parameters | From start of study drug administration up to Week 52 | ECG parameters included assessment of heart rate, sinus rhythm, atrial or ventricular hypertrophy, and assessment of PR, QRS, QT, and corrected QT intervals. Clinically meaningful ECG assessment was based on investigator interpretation. Number of participants with clinically meaningful abnormalities in 12-lead ECG were reported. |
| Renal Function as Assessed by Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 52 | Baseline, Week 52 | Renal function was assessed by eGFR using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula for ≥18 years participants, eGFR = 141 x min (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 \<18 years participants, Counahan-Barratt equation was used for calculation of eGFR. eGFR = (0.43 × height in centimeter \[cm\])/Scr where, Scr is serum creatinine (mg/dL). Renal function as assessed by eGFR was expressed using the unit: milliliters/minute/1.73 meter square (mL/min/1.73m\^2). |
| Change From Baseline in eGFR Values at Weeks 8, 16, 28, and 40 | Baseline, Weeks 8, 16, 28, and 40 | The eGFR was calculated by CKD-EPI formula for ≥18 years participants, eGFR = 141 x min (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 was used for calculation of eGFR. eGFR = (0.43 × height in cm)/Scr where, Scr is serum creatinine (mg/dL). |
| Change From Baseline in Left Ventricular Mass Index (LVMI) at Weeks 16 and 52 | Baseline, Weeks 16 and 52 | LVMI was measured by echocardiography at the clinical sites, and LVMI was derived using the following formula: LVM \[grams\] = 0.8×\[1.04×{(LVDd + IVSTd + PWTd)\^3 - LVDd\^3}\] + 0.6, where: LVDd is left ventricular internal diameter (diastolic) (cm), IVSTd is intraventricular septum thickness (diastolic) (cm), and PWTd is posterior wall thickness (diastolic) (cm). LVM indexed to height (LVMI) = LVM/height\^2.7 (g/m\^2.7), where height was measured in meter. |
| Change From Baseline in Left Ventricular Ejection Fraction (LVEF) at Weeks 16 and 52 | Baseline, Weeks 16 and 52 | LVEF is the central measure of left ventricular systolic function. LVEF is the fraction of chamber volume ejected in systole (stroke volume) in relation to the volume of the blood in the ventricle at the end of diastole (end-diastolic volume). This was measured by echocardiography at the clinical sites. |
| Change From Baseline in Urine Protein/Creatinine Ratio | Baseline, Weeks 8, 16, 28, 40, and 52 | The change from baseline in urine protein/creatinine ratio was derived from early morning spot urine samples collected at the specified time points. |
| Change From Baseline in Brief Pain Inventory (BPI) Short Form Pain Severity Total Score | Baseline, Weeks 8, 16, 28, 40, and 52 | The BPI short form is a numeric rating scale that assesses the severity of pain (severity scale), its impact on daily functioning (Pain Interference scale). BPI short form pain severity scale has been reported here. Pain severity scale 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). The pain severity score is calculated as the average of questions, with a total score ranging from 0 to 10 with higher scores indicating more pain. A negative change from baseline indicates better outcome. |
| Change From Baseline in BPI Short Form Pain Interference Total Score | Baseline, Weeks 8, 16, 28, 40, and 52 | The BPI short form is a numeric rating scale that assesses the severity of pain (severity scale), its impact on daily functioning (Pain Interference scale). BPI short form pain interference scale has been reported here. Pain interference scale has 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). The pain interference score is calculated as the average of questions, with a total score ranging from 0 to 10 with higher scores indicating more interference. A negative change from baseline indicates better outcome. |
| Number of Participants With TEAEs | From start of study drug administration up to 14 days after EOT (up to Week 54) | An AE was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and that did not necessarily have a causal relationship with this investigational product or medicinal product. A TEAE was defined as any event emerging at or after the initiation of treatment with an IP or any existing event that worsened in either intensity or frequency following exposure to the IP until the end of the safety follow-up period. |
| Number of Participants With Hearing Loss as Assessed by Audiology Testing | Baseline up to Week 52 | Hearing loss was assessed in participants with the age \<18 years old by audiology testing. Audiology testing included 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 were to be categorized as conductive, sensorineural, or unknown. |
| Area Under Serum Concentration-time Curve From the Time of Dosing to the Last Measurable Concentration (AUC0-last) of REPLAGAL | 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 | — |
| Area Under Serum Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of REPLAGAL | 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 | — |
| Serum Clearance of Administered Dose (CL) of REPLAGAL | 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 | Clearance is defined as a quantitative measure of the rate at which a drug substance is removed from the body. CL = dose/AUC. |
| Serum Clearance of Administered Dose Normalized Based on Body Weight of REPLAGAL | 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 | Clearance is defined as a quantitative measure of the rate at which a drug substance is removed from the body. CL normalized for body weight was reported. CL= (dose/AUC)/ body weight. Clearance was expressed using the unit: milliliters/minute/kilogram (mL/min/kg). |
| Maximum Observed Serum Concentration (Cmax) of REPLAGAL | 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 | — |
| Terminal Elimination Half-life (T1/2z) of REPLAGAL | 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 | T1/2 is defined as the natural log of 2 divided by the terminal rate constant (ƛz). |
| Time to Reach Maximum Observed Serum Concentration (Tmax) of REPLAGAL | 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 | — |
| Volume of Distribution at Steady State (Vss) of REPLAGAL | 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 | 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. V(ss) = (dose/AUC)\*MRT, where MRT is mean residence time. |
| Volume of Distribution at Steady State Normalized Based on Body Weight of REPLAGAL | 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 | 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 normalized for body weight was reported. V(ss) = \[(dose/AUC)\*MRT\]/ body weight, where MRT is mean residence time. |
| Dose Normalized Area Under Serum Concentration-time Curve From Time Zero to the Last Sampling Time (AUC0-last/Dose) of REPLAGAL | 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 | AUC0-last/Dose was expressed using the unit: (minutes\*units per milliliter)/(units per kilogram) \[(min\*U/mL)/(U/kg)\]. |
| Dose Normalized Area Under the Serum Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-inf/Dose) of REPLAGAL | 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 | — |
| Dose Normalized Maximum Observed Serum Concentration (Cmax/Dose) of REPLAGAL | 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 | Cmax/Dose was expressed using the unit: (units/milliliter)/(units/kilogram) \[(U/mL)/(U/kg)\]. |
| Percent Change From Baseline in Plasma Globotriaosylsphingosine (Lyso-Gb3) Level | Baseline, Weeks 8, 16, 28, 40, and 52 | Plasma lyso-Gb3 determinations were performed at the central laboratory using a validated liquid chromatography-tandem mass spectrometry bioanalytical assay. |
Countries
China
Participant flow
Recruitment details
Participants took part in the study at 6 investigative sites in China from 1 May 2022 to 3 January 2024.
Pre-assignment details
A total of 20 participants with Fabry disease were enrolled in this study to receive REPLAGAL for 52 weeks.
Participants by arm
| Arm | Count |
|---|---|
| REPLAGAL Participants received REPLAGAL 0.2 mg/kg body weight, IV infusion, EOW from Day 1 (Week 0) up to Week 52. | 20 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Gestation | 1 |
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | REPLAGAL |
|---|---|
| Age, Continuous | 30.1 years STANDARD_DEVIATION 14.9 |
| Body Mass Index (BMI) | 20.87 kilograms per meter square (kg/m^2) STANDARD_DEVIATION 3.674 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 20 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Height | 160.47 centimeters (cm) STANDARD_DEVIATION 9.271 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 20 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Sex: Female, Male Female | 12 Participants |
| Sex: Female, Male Male | 8 Participants |
| Weight | 53.88 kilograms (kg) STANDARD_DEVIATION 10.37 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 20 |
| other Total, other adverse events | 18 / 20 |
| serious Total, serious adverse events | 2 / 20 |
Outcome results
Primary
Number of Participants With Serious Treatment-emergent Adverse Events (TEAEs)
An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and that did not necessarily have a causal relationship with this investigational product (IP) or medicinal product. Serious AE was any untoward medical occurrence (whether considered to be related to investigational product or not) that at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital abnormality/birth defect, and was an important medical event. A TEAE was defined as any event emerging at or after the initiation of treatment with an IP or any existing event that worsened in either intensity or frequency following exposure to the IP until the end of the safety follow-up period.
Time frame: From start of study drug administration up to 14 days after end of treatment (EOT) [up to Week 54]
Population: Safety Analysis Set included all participants in the ITT Set who received at least 1 dose of REPLAGAL.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| REPLAGAL | Number of Participants With Serious Treatment-emergent Adverse Events (TEAEs) | 2 Participants |
Secondary
Area Under Serum Concentration-time Curve From the Time of Dosing to the Last Measurable Concentration (AUC0-last) of REPLAGAL
Time frame: 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
Population: Intensive Pharmacokinetic (PK) Set included participants in the PK Set who provided intensive sampling.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| REPLAGAL | Area Under Serum Concentration-time Curve From the Time of Dosing to the Last Measurable Concentration (AUC0-last) of REPLAGAL | Week 0 | 229000 minutes*units per milliliter (min*U/mL) | Standard Deviation 48768 |
| REPLAGAL | Area Under Serum Concentration-time Curve From the Time of Dosing to the Last Measurable Concentration (AUC0-last) of REPLAGAL | Week 28 | 297300 minutes*units per milliliter (min*U/mL) | Standard Deviation 139640 |
Secondary
Area Under Serum Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of REPLAGAL
Time frame: 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
Population: Intensive PK Set included participants in the PK Set who provided intensive sampling.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| REPLAGAL | Area Under Serum Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of REPLAGAL | Week 0 | 233700 min*U/mL | Standard Deviation 49553 |
| REPLAGAL | Area Under Serum Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of REPLAGAL | Week 28 | 309500 min*U/mL | Standard Deviation 157460 |
Secondary
Change From Baseline in BPI Short Form Pain Interference Total Score
The BPI short form is a numeric rating scale that assesses the severity of pain (severity scale), its impact on daily functioning (Pain Interference scale). BPI short form pain interference scale has been reported here. Pain interference scale has 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). The pain interference score is calculated as the average of questions, with a total score ranging from 0 to 10 with higher scores indicating more interference. A negative change from baseline indicates better outcome.
Time frame: Baseline, Weeks 8, 16, 28, 40, and 52
Population: mITT Set included all enrolled participants who had received at least 1 dose of investigational product and completed at least 1 post-baseline efficacy assessment of the endpoints. Overall number analyzed is the number of participants with pain at baseline. Number analyzed is the number of participants with data available for analysis at the specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| REPLAGAL | Change From Baseline in BPI Short Form Pain Interference Total Score | Week 8 | -2.286 score on a scale | Standard Deviation 3.6636 |
| REPLAGAL | Change From Baseline in BPI Short Form Pain Interference Total Score | Week 16 | -3.571 score on a scale | Standard Deviation 3.9812 |
| REPLAGAL | Change From Baseline in BPI Short Form Pain Interference Total Score | Week 28 | -4.738 score on a scale | Standard Deviation 4.3221 |
| REPLAGAL | Change From Baseline in BPI Short Form Pain Interference Total Score | Week 40 | -3.810 score on a scale | Standard Deviation 3.8222 |
| REPLAGAL | Change From Baseline in BPI Short Form Pain Interference Total Score | Week 52 | -3.643 score on a scale | Standard Deviation 5.702 |
Secondary
Change From Baseline in Brief Pain Inventory (BPI) Short Form Pain Severity Total Score
The BPI short form is a numeric rating scale that assesses the severity of pain (severity scale), its impact on daily functioning (Pain Interference scale). BPI short form pain severity scale has been reported here. Pain severity scale 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). The pain severity score is calculated as the average of questions, with a total score ranging from 0 to 10 with higher scores indicating more pain. A negative change from baseline indicates better outcome.
Time frame: Baseline, Weeks 8, 16, 28, 40, and 52
Population: mITT Set included all enrolled participants who had received at least 1 dose of investigational product and completed at least 1 post-baseline efficacy assessment of the endpoints. Overall number analyzed is the number of participants with pain at baseline. Number analyzed is the number of participants with data available for analysis at the specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| REPLAGAL | Change From Baseline in Brief Pain Inventory (BPI) Short Form Pain Severity Total Score | Week 8 | -1.607 score on a scale | Standard Deviation 2.8572 |
| REPLAGAL | Change From Baseline in Brief Pain Inventory (BPI) Short Form Pain Severity Total Score | Week 16 | -2.214 score on a scale | Standard Deviation 2.4041 |
| REPLAGAL | Change From Baseline in Brief Pain Inventory (BPI) Short Form Pain Severity Total Score | Week 28 | -1.833 score on a scale | Standard Deviation 2.6957 |
| REPLAGAL | Change From Baseline in Brief Pain Inventory (BPI) Short Form Pain Severity Total Score | Week 40 | -1.375 score on a scale | Standard Deviation 2.8007 |
| REPLAGAL | Change From Baseline in Brief Pain Inventory (BPI) Short Form Pain Severity Total Score | Week 52 | -0.958 score on a scale | Standard Deviation 3.337 |
Secondary
Change From Baseline in eGFR Values at Weeks 8, 16, 28, and 40
The eGFR was calculated by CKD-EPI formula for ≥18 years participants, eGFR = 141 x min (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 was used for calculation of eGFR. eGFR = (0.43 × height in cm)/Scr where, Scr is serum creatinine (mg/dL).
Time frame: Baseline, Weeks 8, 16, 28, and 40
Population: mITT Set included all enrolled participants who had received at least 1 dose of investigational product and completed at least 1 post-baseline efficacy assessment of the endpoints. Number analyzed is the number of participants with data available for analysis at the specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| REPLAGAL | Change From Baseline in eGFR Values at Weeks 8, 16, 28, and 40 | Week 8 | -1.2 mL/min/1.73m^2 | Standard Deviation 15.66 |
| REPLAGAL | Change From Baseline in eGFR Values at Weeks 8, 16, 28, and 40 | Week 16 | -0.4 mL/min/1.73m^2 | Standard Deviation 13.67 |
| REPLAGAL | Change From Baseline in eGFR Values at Weeks 8, 16, 28, and 40 | Week 28 | 5.1 mL/min/1.73m^2 | Standard Deviation 11.25 |
| REPLAGAL | Change From Baseline in eGFR Values at Weeks 8, 16, 28, and 40 | Week 40 | 0.3 mL/min/1.73m^2 | Standard Deviation 13.17 |
Secondary
Change From Baseline in Left Ventricular Ejection Fraction (LVEF) at Weeks 16 and 52
LVEF is the central measure of left ventricular systolic function. LVEF is the fraction of chamber volume ejected in systole (stroke volume) in relation to the volume of the blood in the ventricle at the end of diastole (end-diastolic volume). This was measured by echocardiography at the clinical sites.
Time frame: Baseline, Weeks 16 and 52
Population: mITT Set included all enrolled participants who had received at least 1 dose of investigational product and completed at least 1 post-baseline efficacy assessment of the endpoints. Number analyzed is the number of participants with data available for analysis at the specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| REPLAGAL | Change From Baseline in Left Ventricular Ejection Fraction (LVEF) at Weeks 16 and 52 | Week 16 | -1.1 percent of LVEF | Standard Deviation 7.29 |
| REPLAGAL | Change From Baseline in Left Ventricular Ejection Fraction (LVEF) at Weeks 16 and 52 | Week 52 | 0.8 percent of LVEF | Standard Deviation 3.28 |
Secondary
Change From Baseline in Left Ventricular Mass Index (LVMI) at Weeks 16 and 52
LVMI was measured by echocardiography at the clinical sites, and LVMI was derived using the following formula: LVM \[grams\] = 0.8×\[1.04×{(LVDd + IVSTd + PWTd)\^3 - LVDd\^3}\] + 0.6, where: LVDd is left ventricular internal diameter (diastolic) (cm), IVSTd is intraventricular septum thickness (diastolic) (cm), and PWTd is posterior wall thickness (diastolic) (cm). LVM indexed to height (LVMI) = LVM/height\^2.7 (g/m\^2.7), where height was measured in meter.
Time frame: Baseline, Weeks 16 and 52
Population: mITT Set included all enrolled participants who had received at least 1 dose of investigational product and completed at least 1 post-baseline efficacy assessment of the endpoints. Number analyzed is the number of participants with data available for analysis at the specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| REPLAGAL | Change From Baseline in Left Ventricular Mass Index (LVMI) at Weeks 16 and 52 | Week 16 | -0.4696 grams per meter (g/m)^2.7 | Standard Deviation 6.81928 |
| REPLAGAL | Change From Baseline in Left Ventricular Mass Index (LVMI) at Weeks 16 and 52 | Week 52 | -1.7261 grams per meter (g/m)^2.7 | Standard Deviation 9.87836 |
Secondary
Change From Baseline in Urine Protein/Creatinine Ratio
The change from baseline in urine protein/creatinine ratio was derived from early morning spot urine samples collected at the specified time points.
Time frame: Baseline, Weeks 8, 16, 28, 40, and 52
Population: mITT Set included all enrolled participants who had received at least 1 dose of investigational product and completed at least 1 post-baseline efficacy assessment of the endpoints. Number analyzed is the number of participants with data available for analysis at the specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| REPLAGAL | Change From Baseline in Urine Protein/Creatinine Ratio | Week 28 | 0.0711 gram per gram | Standard Deviation 0.16049 |
| REPLAGAL | Change From Baseline in Urine Protein/Creatinine Ratio | Week 40 | 0.0830 gram per gram | Standard Deviation 0.16333 |
| REPLAGAL | Change From Baseline in Urine Protein/Creatinine Ratio | Week 52 | 0.0627 gram per gram | Standard Deviation 0.16508 |
| REPLAGAL | Change From Baseline in Urine Protein/Creatinine Ratio | Week 8 | 0.0759 gram per gram | Standard Deviation 0.17486 |
| REPLAGAL | Change From Baseline in Urine Protein/Creatinine Ratio | Week 16 | 0.1061 gram per gram | Standard Deviation 0.21743 |
Secondary
Dose Normalized Area Under Serum Concentration-time Curve From Time Zero to the Last Sampling Time (AUC0-last/Dose) of REPLAGAL
AUC0-last/Dose was expressed using the unit: (minutes\*units per milliliter)/(units per kilogram) \[(min\*U/mL)/(U/kg)\].
Time frame: 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
Population: Intensive PK Set included participants in the PK Set who provided intensive sampling.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| REPLAGAL | Dose Normalized Area Under Serum Concentration-time Curve From Time Zero to the Last Sampling Time (AUC0-last/Dose) of REPLAGAL | Week 0 | 0.005411 (min*U/mL)/(U/kg) | Standard Deviation 0.0010847 |
| REPLAGAL | Dose Normalized Area Under Serum Concentration-time Curve From Time Zero to the Last Sampling Time (AUC0-last/Dose) of REPLAGAL | Week 28 | 0.008119 (min*U/mL)/(U/kg) | Standard Deviation 0.0044732 |
Secondary
Dose Normalized Area Under the Serum Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-inf/Dose) of REPLAGAL
Time frame: 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
Population: Intensive PK Set included participants in the PK Set who provided intensive sampling.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| REPLAGAL | Dose Normalized Area Under the Serum Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-inf/Dose) of REPLAGAL | Week 0 | 0.005520 (min*U/mL)/(U/kg) | Standard Deviation 0.0010993 |
| REPLAGAL | Dose Normalized Area Under the Serum Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-inf/Dose) of REPLAGAL | Week 28 | 0.008489 (min*U/mL)/(U/kg) | Standard Deviation 0.0051204 |
Secondary
Dose Normalized Maximum Observed Serum Concentration (Cmax/Dose) of REPLAGAL
Cmax/Dose was expressed using the unit: (units/milliliter)/(units/kilogram) \[(U/mL)/(U/kg)\].
Time frame: 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
Population: Intensive PK Set included participants in the PK Set who provided intensive sampling.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| REPLAGAL | Dose Normalized Maximum Observed Serum Concentration (Cmax/Dose) of REPLAGAL | Week 0 | 0.0001092 (U/mL)/(U/kg) | Standard Deviation 0.000021579 |
| REPLAGAL | Dose Normalized Maximum Observed Serum Concentration (Cmax/Dose) of REPLAGAL | Week 28 | 0.0001197 (U/mL)/(U/kg) | Standard Deviation 0.000040471 |
Secondary
Maximum Observed Serum Concentration (Cmax) of REPLAGAL
Time frame: 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
Population: Intensive PK Set included participants in the PK Set who provided intensive sampling.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| REPLAGAL | Maximum Observed Serum Concentration (Cmax) of REPLAGAL | Week 0 | 4620.55 units per milliliter (U/mL) | Standard Deviation 1046.889 |
| REPLAGAL | Maximum Observed Serum Concentration (Cmax) of REPLAGAL | Week 28 | 4507.99 units per milliliter (U/mL) | Standard Deviation 1682.041 |
Secondary
Number of Participants With Clinically Meaningful Changes in Electrocardiogram (ECG) Parameters
ECG parameters included assessment of heart rate, sinus rhythm, atrial or ventricular hypertrophy, and assessment of PR, QRS, QT, and corrected QT intervals. Clinically meaningful ECG assessment was based on investigator interpretation. Number of participants with clinically meaningful abnormalities in 12-lead ECG were reported.
Time frame: From start of study drug administration up to Week 52
Population: Safety Analysis Set included all participants in the ITT Set who received at least 1 dose of REPLAGAL.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| REPLAGAL | Number of Participants With Clinically Meaningful Changes in Electrocardiogram (ECG) Parameters | 0 Participants |
Secondary
Number of Participants With Clinically Meaningful Changes in Laboratory Parameters
Laboratory assessment included parameters of serum chemistry, hematology, and urinalysis. Clinically meaningful laboratory parameters assessment was based on investigator interpretation. Number of participants with clinically meaningful changes in laboratory parameters were reported.
Time frame: From start of study drug administration up to Week 52
Population: Safety Analysis Set included all participants in the ITT Set who received at least 1 dose of REPLAGAL.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| REPLAGAL | Number of Participants With Clinically Meaningful Changes in Laboratory Parameters | 0 Participants |
Secondary
Number of Participants With Clinically Meaningful Changes in Vital Signs
Vital sign assessment included pulse, blood pressure, respiratory rate, and temperature. Clinically meaningful vital signs assessment was based on investigator interpretation. Number of participants with clinically meaningful abnormalities in vital signs were reported.
Time frame: From start of study drug administration up to Week 52
Population: Safety Analysis Set included all participants in the ITT Set who received at least 1 dose of REPLAGAL.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| REPLAGAL | Number of Participants With Clinically Meaningful Changes in Vital Signs | 0 Participants |
Secondary
Number of Participants With Hearing Loss as Assessed by Audiology Testing
Hearing loss was assessed in participants with the age \<18 years old by audiology testing. Audiology testing included 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 were to be categorized as conductive, sensorineural, or unknown.
Time frame: Baseline up to Week 52
Population: mITT Set included all enrolled participants who had received at least 1 dose of investigational product and completed at least 1 post-baseline efficacy assessment of the endpoints. Overall number analyzed is the number of participants with age \<18 years old.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| REPLAGAL | Number of Participants With Hearing Loss as Assessed by Audiology Testing | 0 Participants |
Secondary
Number of Participants With Infusion-related Reactions (IRRs)
An IRR was defined as an event that began either during or within 24 hours after the start of the infusion, and was judged as related to treatment with the IP. An IRR could be serious or non-serious. Adverse events that were considered IRRs were noted as such in the participant's source documentation. Other AEs which occurred 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, were not considered as IRRs.
Time frame: From start of study drug administration up to Week 52
Population: Safety Analysis Set included all participants in the ITT Set who received at least 1 dose of REPLAGAL.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| REPLAGAL | Number of Participants With Infusion-related Reactions (IRRs) | 5 Participants |
Secondary
Number of Participants With Positive Anti-drug Antibodies (ADA) to REPLAGAL
Number of participants with positive ADA to REPLAGAL were reported.
Time frame: Baseline up to Week 52
Population: Safety Analysis Set included all participants in the ITT Set who received at least 1 dose of REPLAGAL.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| REPLAGAL | Number of Participants With Positive Anti-drug Antibodies (ADA) to REPLAGAL | 6 Participants |
Secondary
Number of Participants With Positive Neutralizing Antibodies (NAb) to REPLAGAL
Number of participants with positive NAb to REPLAGAL were reported.
Time frame: Baseline up to Week 52
Population: Safety Analysis Set included all participants in the ITT Set who received at least 1 dose of REPLAGAL.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| REPLAGAL | Number of Participants With Positive Neutralizing Antibodies (NAb) to REPLAGAL | 5 Participants |
Secondary
Number of Participants With TEAEs
An AE was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and that did not necessarily have a causal relationship with this investigational product or medicinal product. A TEAE was defined as any event emerging at or after the initiation of treatment with an IP or any existing event that worsened in either intensity or frequency following exposure to the IP until the end of the safety follow-up period.
Time frame: From start of study drug administration up to 14 days after EOT (up to Week 54)
Population: Safety Analysis Set included all participants in the ITT Set who received at least 1 dose of REPLAGAL.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| REPLAGAL | Number of Participants With TEAEs | 20 Participants |
Secondary
Percent Change From Baseline in Plasma Globotriaosylsphingosine (Lyso-Gb3) Level
Plasma lyso-Gb3 determinations were performed at the central laboratory using a validated liquid chromatography-tandem mass spectrometry bioanalytical assay.
Time frame: Baseline, Weeks 8, 16, 28, 40, and 52
Population: mITT Set included all enrolled participants who had received at least 1 dose of investigational product and completed at least 1 post-baseline efficacy assessment of the endpoints. Number analyzed is the number of participants with data available for analysis at the specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| REPLAGAL | Percent Change From Baseline in Plasma Globotriaosylsphingosine (Lyso-Gb3) Level | Week 8 | -36.236 percent change | Standard Deviation 24.7056 |
| REPLAGAL | Percent Change From Baseline in Plasma Globotriaosylsphingosine (Lyso-Gb3) Level | Week 16 | -38.147 percent change | Standard Deviation 24.7376 |
| REPLAGAL | Percent Change From Baseline in Plasma Globotriaosylsphingosine (Lyso-Gb3) Level | Week 28 | -37.764 percent change | Standard Deviation 25.8314 |
| REPLAGAL | Percent Change From Baseline in Plasma Globotriaosylsphingosine (Lyso-Gb3) Level | Week 40 | -35.565 percent change | Standard Deviation 27.7874 |
| REPLAGAL | Percent Change From Baseline in Plasma Globotriaosylsphingosine (Lyso-Gb3) Level | Week 52 | -37.072 percent change | Standard Deviation 27.5659 |
Secondary
Renal Function as Assessed by Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 52
Renal function was assessed by eGFR using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula for ≥18 years participants, eGFR = 141 x min (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 \<18 years participants, Counahan-Barratt equation was used for calculation of eGFR. eGFR = (0.43 × height in centimeter \[cm\])/Scr where, Scr is serum creatinine (mg/dL). Renal function as assessed by eGFR was expressed using the unit: milliliters/minute/1.73 meter square (mL/min/1.73m\^2).
Time frame: Baseline, Week 52
Population: Modified Intent-to-treat (mITT) Set included all enrolled participants who had received at least 1 dose of investigational product and completed at least 1 post-baseline efficacy assessment of the endpoints.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| REPLAGAL | Renal Function as Assessed by Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 52 | 4.1 mL/min/1.73m^2 | Standard Deviation 12.48 |
Secondary
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 = dose/AUC.
Time frame: 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
Population: Intensive PK Set included participants in the PK Set who provided intensive sampling.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| REPLAGAL | Serum Clearance of Administered Dose (CL) of REPLAGAL | Week 0 | 187.4 milliliters per minute (mL/min) | Standard Deviation 35.77 |
| REPLAGAL | Serum Clearance of Administered Dose (CL) of REPLAGAL | Week 28 | 195.5 milliliters per minute (mL/min) | Standard Deviation 226.52 |
Secondary
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 normalized for body weight was reported. CL= (dose/AUC)/ body weight. Clearance was expressed using the unit: milliliters/minute/kilogram (mL/min/kg).
Time frame: 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
Population: Intensive PK Set included participants in the PK Set who provided intensive sampling.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| REPLAGAL | Serum Clearance of Administered Dose Normalized Based on Body Weight of REPLAGAL | Week 0 | 3.234 mL/min/kg | Standard Deviation 0.7807 |
| REPLAGAL | Serum Clearance of Administered Dose Normalized Based on Body Weight of REPLAGAL | Week 28 | 3.183 mL/min/kg | Standard Deviation 3.5632 |
Secondary
Terminal Elimination Half-life (T1/2z) of REPLAGAL
T1/2 is defined as the natural log of 2 divided by the terminal rate constant (ƛz).
Time frame: 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
Population: Intensive PK Set included participants in the PK Set who provided intensive sampling.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| REPLAGAL | Terminal Elimination Half-life (T1/2z) of REPLAGAL | Week 0 | 45.36 minutes | Standard Deviation 23.058 |
| REPLAGAL | Terminal Elimination Half-life (T1/2z) of REPLAGAL | Week 28 | 66.34 minutes | Standard Deviation 27.272 |
Secondary
Time to Reach Maximum Observed Serum Concentration (Tmax) of REPLAGAL
Time frame: 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
Population: Intensive PK Set included participants in the PK Set who provided intensive sampling.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| REPLAGAL | Time to Reach Maximum Observed Serum Concentration (Tmax) of REPLAGAL | Week 0 | 40.000 hours |
| REPLAGAL | Time to Reach Maximum Observed Serum Concentration (Tmax) of REPLAGAL | Week 28 | 40.000 hours |
Secondary
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 normalized for body weight was reported. V(ss) = \[(dose/AUC)\*MRT\]/ body weight, where MRT is mean residence time.
Time frame: 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
Population: Intensive PK Set included participants in the PK Set who provided intensive sampling.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| REPLAGAL | Volume of Distribution at Steady State Normalized Based on Body Weight of REPLAGAL | Week 28 | 202.1 milliliters per kilogram (mL/kg) | Standard Deviation 267.74 |
| REPLAGAL | Volume of Distribution at Steady State Normalized Based on Body Weight of REPLAGAL | Week 0 | 135.9 milliliters per kilogram (mL/kg) | Standard Deviation 34.53 |
Secondary
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. V(ss) = (dose/AUC)\*MRT, where MRT is mean residence time.
Time frame: 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
Population: Intensive PK Set included participants in the PK Set who provided intensive sampling.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| REPLAGAL | Volume of Distribution at Steady State (Vss) of REPLAGAL | Week 0 | 7834 milliliters (mL) | Standard Deviation 1625.9 |
| REPLAGAL | Volume of Distribution at Steady State (Vss) of REPLAGAL | Week 28 | 12310 milliliters (mL) | Standard Deviation 16988 |