Clinical Trial Results:
An Open-label Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of REPLAGAL® in Treatment-naïve Chinese Subjects with Fabry Disease
Summary
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EudraCT number |
2022-004246-35 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
03 Jan 2024
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Results information
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Results version number |
v1(current) |
This version publication date |
18 Jul 2024
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First version publication date |
18 Jul 2024
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Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
TAK-675-3001
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT04974749 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Takeda
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Sponsor organisation address |
95 Hayden Avenue, Lexington, United States, MA 02421
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Public contact |
Study Director, Takeda, TrialDisclosures@takeda.com
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Scientific contact |
Study Director, Takeda, TrialDisclosures@takeda.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
Yes
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
03 Jan 2024
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
03 Jan 2024
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The main purpose of this study is to assess the safety of REPLAGAL in treatment-naïve Chinese participants with Fabry disease.
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Protection of trial subjects |
Each participant signed an informed consent form (ICF) before participating in the study.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
01 May 2022
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
China: 20
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Worldwide total number of subjects |
20
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EEA total number of subjects |
0
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
2
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Adolescents (12-17 years) |
5
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Adults (18-64 years) |
13
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
Participants took part in the study at 6 investigative sites in China from 1 May 2022 to 3 January 2024. | ||||||||||||
Pre-assignment
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Screening details |
A total of 20 participants with Fabry disease were enrolled in this study to receive REPLAGAL for 52 weeks. | ||||||||||||
Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||||||||
Allocation method |
Non-randomised - controlled
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Blinding used |
Not blinded | ||||||||||||
Arms
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Arm title
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REPLAGAL | ||||||||||||
Arm description |
Participants received REPLAGAL 0.2 milligrams per kilogram (mg/kg) body weight, intravenous (IV) infusion, every other week (EOW) from Day 1 (Week 0) up to Week 52. | ||||||||||||
Arm type |
Experimental | ||||||||||||
Investigational medicinal product name |
REPLAGAL
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Investigational medicinal product code |
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Other name |
Agalsidase Alfa, TAK-675
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Pharmaceutical forms |
Solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Participants received REPLAGAL 0.2 mg/kg body weight, infusion, IV, EOW for 52 weeks.
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Baseline characteristics reporting groups
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Reporting group title |
REPLAGAL
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Reporting group description |
Participants received REPLAGAL 0.2 milligrams per kilogram (mg/kg) body weight, intravenous (IV) infusion, every other week (EOW) from Day 1 (Week 0) up to Week 52. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
REPLAGAL
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Reporting group description |
Participants received REPLAGAL 0.2 milligrams per kilogram (mg/kg) body weight, intravenous (IV) infusion, every other week (EOW) from Day 1 (Week 0) up to Week 52. |
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End point title |
Number of Participants With Serious Treatment-emergent Adverse Events (TEAEs) [1] | ||||||
End point description |
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. Safety Analysis Set included all participants in the ITT Set who received at least 1 dose of REPLAGAL.
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End point type |
Primary
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End point timeframe |
From start of study drug administration up to 14 days after end of treatment (EOT) [up to Week 54]
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Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Only descriptive analysis was planned for this endpoint. |
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No statistical analyses for this end point |
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End point title |
Number of Participants With TEAEs | ||||||
End point description |
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. Safety Analysis Set included all participants in the Intent-to-treat (ITT) Set who received at least 1 dose of REPLAGAL.
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End point type |
Secondary
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End point timeframe |
From start of study drug administration up to 14 days after EOT (up to Week 54)
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No statistical analyses for this end point |
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End point title |
Number of Participants With Infusion-related Reactions (IRRs) | ||||||
End point description |
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. Safety Analysis Set included all participants in the ITT Set who received at least 1 dose of REPLAGAL.
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End point type |
Secondary
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End point timeframe |
From start of study drug administration up to Week 52
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No statistical analyses for this end point |
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End point title |
Number of Participants With Clinically Meaningful Changes in Laboratory Parameters | ||||||
End point description |
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. Safety Analysis Set included all participants in the ITT Set who received at least 1 dose of REPLAGAL.
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End point type |
Secondary
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End point timeframe |
From start of study drug administration up to Week 52
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No statistical analyses for this end point |
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End point title |
Number of Participants With Positive Neutralizing Antibodies (NAb) to REPLAGAL | ||||||
End point description |
Number of participants with positive NAb to REPLAGAL were reported. Safety Analysis Set included all participants in the ITT Set who received at least 1 dose of REPLAGAL.
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End point type |
Secondary
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End point timeframe |
Baseline up to Week 52
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No statistical analyses for this end point |
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End point title |
Number of Participants With Positive Anti-drug Antibodies (ADA) to REPLAGAL | ||||||
End point description |
Number of participants with positive ADA to REPLAGAL were reported. Safety Analysis Set included all participants in the ITT Set who received at least 1 dose of REPLAGAL.
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End point type |
Secondary
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End point timeframe |
Baseline up to Week 52
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No statistical analyses for this end point |
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End point title |
Number of Participants With Clinically Meaningful Changes in Electrocardiogram (ECG) Parameters | ||||||
End point description |
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. Safety Analysis Set included all participants in the ITT Set who received at least 1 dose of REPLAGAL.
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End point type |
Secondary
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End point timeframe |
From start of study drug administration up to Week 52
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No statistical analyses for this end point |
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End point title |
Renal Function as Assessed by Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 52 | ||||||||
End point description |
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). 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.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 52
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No statistical analyses for this end point |
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End point title |
Change From Baseline in eGFR Values at Weeks 8, 16, 28, and 40 | ||||||||||||||||
End point description |
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). 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. 'n' denotes the number of participants with data available for analysis at the specified timepoint.
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End point type |
Secondary
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End point timeframe |
Baseline, Weeks 8, 16, 28, and 40
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No statistical analyses for this end point |
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End point title |
Number of Participants With Clinically Meaningful Changes in Vital Signs | ||||||
End point description |
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. Safety Analysis Set included all participants in the ITT Set who received at least 1 dose of REPLAGAL.
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End point type |
Secondary
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End point timeframe |
From start of study drug administration up to Week 52
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No statistical analyses for this end point |
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End point title |
Change From Baseline in Left Ventricular Mass Index (LVMI) at Weeks 16 and 52 | ||||||||||||
End point description |
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. 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. 'n' denotes the number of participants with data available for analysis at the specified timepoint.
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End point type |
Secondary
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End point timeframe |
Baseline, Weeks 16 and 52
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No statistical analyses for this end point |
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End point title |
Change From Baseline in Left Ventricular Ejection Fraction (LVEF) at Weeks 16 and 52 | ||||||||||||
End point description |
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. 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. 'n' denotes the number of participants with data available for analysis at the specified timepoint.
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End point type |
Secondary
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End point timeframe |
Baseline, Weeks 16 and 52
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No statistical analyses for this end point |
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End point title |
Change From Baseline in Urine Protein/Creatinine Ratio | ||||||||||||||||||
End point description |
The change from baseline in urine protein/creatinine ratio was derived from early morning spot urine samples collected at the specified time points. 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. 'n' denotes the number of participants with data available for analysis at the specified timepoint.
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End point type |
Secondary
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End point timeframe |
Baseline, Weeks 8, 16, 28, 40, and 52
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No statistical analyses for this end point |
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End point title |
Change From Baseline in Brief Pain Inventory (BPI) Short Form Pain Severity Total Score | ||||||||||||||||||
End point description |
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. 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. Subjects analyzed is the number of participants with pain at baseline. 'n' denotes the number of participants with data available for analysis at the specified timepoint.
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End point type |
Secondary
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End point timeframe |
Baseline, Weeks 8, 16, 28, 40, and 52
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No statistical analyses for this end point |
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End point title |
Change From Baseline in BPI Short Form Pain Interference Total Score | ||||||||||||||||||
End point description |
BPI short form is numeric rating scale that assesses 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).Pain interference score=average of questions, with total score ranging from 0-10 with higher scores indicating more interference. Negative change from baseline indicates better outcome. mITT Set included all enrolled participants who had received at least 1 dose of investigational product & completed at least 1 post-baseline efficacy assessment of endpoints. Subjects analyzed is number of participants with pain at baseline. 'n' denotes number of participants with data available for analysis at the specified timepoint.
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End point type |
Secondary
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End point timeframe |
Baseline, Weeks 8, 16, 28, 40, and 52
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No statistical analyses for this end point |
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End point title |
Percent Change From Baseline in Plasma Globotriaosylsphingosine (Lyso-Gb3) Level | ||||||||||||||||||
End point description |
Plasma lyso-Gb3 determinations were performed at the central laboratory using a validated liquid chromatography-tandem mass spectrometry bioanalytical assay. 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. 'n' denotes the number of participants with data available for analysis at the specified timepoint.
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End point type |
Secondary
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End point timeframe |
Baseline, Weeks 8, 16, 28, 40, and 52
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No statistical analyses for this end point |
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End point title |
Number of Participants With Hearing Loss as Assessed by Audiology Testing | ||||||
End point description |
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. 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. Subjects analyzed is the number of participants with age <18 years old.
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End point type |
Secondary
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End point timeframe |
Baseline up to Week 52
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No statistical analyses for this end point |
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End point title |
Serum Clearance of Administered Dose (CL) of REPLAGAL | ||||||||||||
End point description |
Clearance is defined as a quantitative measure of the rate at which a drug substance is removed from the body. CL = dose/AUC. Intensive PK Set included participants in the PK Set who provided intensive sampling.
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End point type |
Secondary
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End point 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
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No statistical analyses for this end point |
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End point title |
Area Under Serum Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of REPLAGAL | ||||||||||||
End point description |
Intensive PK Set included participants in the PK Set who provided intensive sampling.
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End point type |
Secondary
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End point 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
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No statistical analyses for this end point |
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End point title |
Area Under Serum Concentration-time Curve From the Time of Dosing to the Last Measurable concentration (AUC0-last) of REPLAGAL | ||||||||||||
End point description |
Intensive Pharmacokinetic (PK) Set included participants in the PK Set who provided intensive sampling.
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End point type |
Secondary
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End point 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
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No statistical analyses for this end point |
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End point title |
Maximum Observed Serum Concentration (Cmax) of REPLAGAL | ||||||||||||
End point description |
Intensive PK Set included participants in the PK Set who provided intensive sampling.
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End point type |
Secondary
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End point 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
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No statistical analyses for this end point |
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End point title |
Terminal Elimination Half-life (T1/2z) of REPLAGAL | ||||||||||||
End point description |
T1/2 is defined as the natural log of 2 divided by the terminal rate constant (ƛz). Intensive PK Set included participants in the PK Set who provided intensive sampling.
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End point type |
Secondary
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End point 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
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No statistical analyses for this end point |
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End point title |
Serum Clearance of Administered Dose Normalized Based on Body Weight of REPLAGAL | ||||||||||||
End point description |
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). Intensive PK Set included participants in the PK Set who provided intensive sampling.
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End point type |
Secondary
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End point 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
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No statistical analyses for this end point |
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End point title |
Time to Reach Maximum Observed Serum Concentration (Tmax) of REPLAGAL | ||||||||||||
End point description |
Intensive PK Set included participants in the PK Set who provided intensive sampling.
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End point type |
Secondary
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End point 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
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No statistical analyses for this end point |
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End point title |
Volume of Distribution at Steady State Normalized Based on Body Weight of REPLAGAL | ||||||||||||
End point description |
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. Intensive PK Set included participants in the PK Set who provided intensive sampling.
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End point type |
Secondary
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End point 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
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No statistical analyses for this end point |
|
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End point title |
Volume of Distribution at Steady State (Vss) of REPLAGAL | ||||||||||||
End point description |
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. Intensive PK Set included participants in the PK Set who provided intensive sampling.
|
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End point type |
Secondary
|
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End point 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
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
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End point title |
Dose Normalized Maximum Observed Serum Concentration (Cmax/Dose) of REPLAGAL | ||||||||||||
End point description |
Cmax/Dose was expressed using the unit: (units/milliliter)/(units/kilogram) [(U/mL)/(U/kg)]. Intensive PK Set included participants in the PK Set who provided intensive sampling.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point 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
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Dose Normalized Area Under the Serum Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-inf/Dose) of REPLAGAL | ||||||||||||
End point description |
Intensive PK Set included participants in the PK Set who provided intensive sampling.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point 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
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Dose Normalized Area Under Serum Concentration-time Curve From Time Zero to the Last Sampling Time (AUC0-last/Dose) of REPLAGAL | ||||||||||||
End point description |
AUC0-last/Dose was expressed using the unit: (minutes*units per milliliter)/(units per kilogram) [(min*U/mL)/(U/kg)]. Intensive PK Set included participants in the PK Set who provided intensive sampling.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point 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
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse events information
|
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Timeframe for reporting adverse events |
From start of study drug administration up to 14 days after EOT (up to Week 54)
|
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Adverse event reporting additional description |
Safety Analysis Set included all participants in the ITT Set who received at least 1 dose of REPLAGAL.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
|
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
26.1
|
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Reporting groups
|
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Reporting group title |
REPLAGAL
|
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Reporting group description |
Participants received REPLAGAL 0.2 mg/kg body weight, IV infusion, EOW from Day 1 (Week 0) up to Week 52. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
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Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
Substantial protocol amendments (globally) |
|||
Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
07 Feb 2022 |
The following changes were made as per Amendment 1: 1) Added cardiac LVMI and LVEF assessed by echocardiography test as one of the efficacy assessments. 2) Updated inclusion and exclusion criteria. 3) Added and clarified that the mITT analysis set will be used for efficacy analyses, instead of the ITT set. 4) Updated time points for height and weight measurement. 5) Removed the requirement that participants need to fast for at least 8 hours prior to the blood draw for plasma lyso-Gb3 assessment. |
||
23 May 2023 |
The following changes were made as per Amendment 2: 1) Added EudraCT number. 2) Updated inclusion criteria. 3) Modified the ITT definition to include all participants enrolled in the study. 4) Added description of BMI calculation. 5) Added ‘physical examination finding’ to the list of clinical assessments. |
||
Interruptions (globally) |
|||
Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |