Clinical Trial Results:
Open-Label Extension Study to Evaluate the Long-Term Safety and Efficacy of Pegunigalsidase Alfa (PRX-102) in Patients With Fabry Disease
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Summary
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EudraCT number |
2018-001148-67 |
Trial protocol |
GB NO CZ ES SI NL HU IT FI FR |
Global end of trial date |
21 Jan 2025
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Results information
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Results version number |
v1(current) |
This version publication date |
04 Jan 2026
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First version publication date |
04 Jan 2026
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Other versions |
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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 |
CLI-06657AA1-04
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03566017 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Chiesi Farmaceutici S.p.A.
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Sponsor organisation address |
Via Palermo 26/A, Parma, Italy, 43122
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Public contact |
Clinical Trial Transparency, Chiesi Farmaceutici S.p.A., +39 05212791, clinicaltrials_info@chiesi.com
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Scientific contact |
Clinical Trial Transparency, Chiesi Farmaceutici S.p.A., +39 05212791, clinicaltrials_info@chiesi.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? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
13 Oct 2025
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
21 Jan 2025
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Global end of trial reached? |
Yes
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Global end of trial date |
21 Jan 2025
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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 |
To evaluate the ongoing safety, tolerability and efficacy parameters of 1 mg/kg pegunigalsidase alfa every 2 weeks in adult patients with Fabry disease who have completed studies PB-102-F20 or PB-102-F30 or completed at least 48 months in study PB-102-F03.
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Protection of trial subjects |
Safety was monitored throughout. For subjects who received pegunigalsidase alfa in studies PB-102-F03/F30, the first infusion in study CLI-06657AA1-04 was of the same duration (but not <60 minutes [min]), with the same premedication (if used) and post-dose observation of 60 min. Subjects had received pegunigalsidase alfa or agalsidase beta in study PB-102-F20. The blind was still maintained for study PB-102-F20 when subjects enrolled in study CLI-06657AA1-04. As some subjects would receive pegunigalsidase alfa for the first time, the duration of the first infusion was 3 hours, with premedication (if used) and with post-dose observation of 2 hours. Subsequent infusions and premedications were managed as per protocol-specified guidance for all enrolled subjects. Tolerability was assessed during infusions and subjects were monitored for hypersensitivity, anaphylaxis and anaphylactoid reactions during and after infusions. Adverse events and concomitant medications were collected throughout. Vital signs were assessed pre-infusion, every 30 min in the first hour, every 60 min during observation and at the end of observation. Safety, pain and quality of life (QoL) assessments were performed 6-monthly (more often in the first year for subjects who enrolled from study PB-102-F20) : physical examination, recording of body weight, electrocardiograms (ECGs), laboratory tests (haematology, biochemistry, urinalysis, anti-drug antibodies [ADA], serum creatinine and cystatin C), short form Brief Pain Inventory (BPI) and EuroQoL-5 Dimensions-5 Levels (EQ-5D-5L) questionnaire. Cardiac function and exercise tolerance were assessed 12-monthly by magnetic resonance imaging (MRI)/echocardiogram and stress test, respectively. Brain MRI was performed 24-monthly. Regular phone calls were made to subjects receiving home infusions. Pregnancy tests were performed in females of childbearing potential. Measures to protect subjects during the coronavirus pandemic were included in study plans.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
16 Sep 2018
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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 |
Australia: 1
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Country: Number of subjects enrolled |
Canada: 2
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Country: Number of subjects enrolled |
United States: 55
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Country: Number of subjects enrolled |
Netherlands: 6
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Country: Number of subjects enrolled |
Norway: 3
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Country: Number of subjects enrolled |
Slovenia: 2
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Country: Number of subjects enrolled |
Spain: 5
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Country: Number of subjects enrolled |
United Kingdom: 9
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Country: Number of subjects enrolled |
Czechia: 9
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Country: Number of subjects enrolled |
Finland: 1
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Country: Number of subjects enrolled |
France: 1
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Country: Number of subjects enrolled |
Hungary: 1
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Country: Number of subjects enrolled |
Italy: 2
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Worldwide total number of subjects |
97
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EEA total number of subjects |
30
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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) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
97
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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 |
Subjects who had completed studies PB-102-F20 or PB-102-F30 or at least 48 months in study PB-102-F03 were enrolled. The first subject first visit was on 16 September 2018. There were 30 study centres in 13 countries. | ||||||||||||||||||||
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Pre-assignment
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Screening details |
The trial was an extension of studies PB-102-F03/F20/F30. The Screening Visit was the last visit of the previous trial and all information at these visits was included as the screening information for study CLI-06657AA1-04. Subjects from study PB-102-F03 had additional screening assessments of serum creatinine and cystatin C and QoL. | ||||||||||||||||||||
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Period 1
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Period 1 title |
Overall trial (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||||||||
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Arms
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Arm title
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Overall population | ||||||||||||||||||||
Arm description |
All subjects received pegunigalsidase alfa 1 mg/kg by intravenous infusion every 2 weeks. | ||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||
Investigational medicinal product name |
Pegunigalsidase alfa
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Investigational medicinal product code |
Pegunigalsidase alfa
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Other name |
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Pharmaceutical forms |
Concentrate for solution for infusion
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Routes of administration |
Infusion
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Dosage and administration details |
Pegunigalsidase alfa was administered at a dose of 1 mg/kg every 2 weeks (±3 days) by intravenous infusion. For each subject, the dose was prepared according to their screening weight and adjusted according to their weight every 6 months if the weight had changed by 25% from the previous adjustment. The total volume of infusion was adjusted with normal saline to a final volume of 150, 250 or 500 mL per infusion for subjects weighing 70, 70-100 or >100 kg, respectively and recalculated only if dose was adjusted. Infusion rate was adjusted according to individual symptoms/signs as per protocol-specified guidance.
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Baseline characteristics reporting groups
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Reporting group title |
Overall trial
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Overall population
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Reporting group description |
All subjects received pegunigalsidase alfa 1 mg/kg by intravenous infusion every 2 weeks. | ||
Subject analysis set title |
Intent-to-treat (ITT) Population excluding Cohort F03
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Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
Some efficacy variables were assessed in the ITT Population excluding subjects enrolled from study PB-102-F03 (Cohort F03). The ITT Population excluding Cohort F03 included 87 subjects. Plasma Lyso-Gb3 was assessed in different laboratories in studies PB-102-F01/F02/F03 and in studies PB-102-F20, PB-102-F30 and CLI-06657AA1-04. Plasma globotriaosylceramide (Gb3) was assessed in a different unit in in studies PB-102-F01/F02/F03 and in studies PB-102-F20, PB-102-F30 and CLI-06657AA1-04 and conversion between the units was not possible. The EQ-5D-5L questionnaire was not administered during study PB-102-F03. Change from baseline for these variables was assessed in the pooled sample of subjects enrolled from studies PB-102-F20 and PB-102-F30.
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Subject analysis set title |
Safety Population excluding Cohort F03
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
Infusion premedications were not collected in studies PB-102-F01/F02/F03; analysis of infusion premedications was performed separately in the Safety Population excluding Cohort F03.
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Subject analysis set title |
ITT Population
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Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
The ITT population included all subjects who provided informed consent for study CLI-06657AA1-04 and received any dose, including a partial dose of pegunigalsidase alfa in study CLI-06657AA1-04.
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Subject analysis set title |
Safety Population
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
The Safety Population included all subjects who provided informed consent for study CLI-06657AA1-04 and received any dose, including a partial dose of pegunigalsidase alfa in study CLI-06657AA1-04.
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End point title |
Number of subjects with treatment-related adverse events (AEs) [1] | ||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
No primary or secondary endpoints were specified. Evaluation of safety was a main objective.
A treatment-emergent AE (TEAE) was defined as any AE occurring after the start of study treatment and within the time of residual drug effect (20 days after the last administration of study treatment) or a pre-treatment AE or pre-existing medical condition that worsened in severity after the start of study treatment and within the time of residual drug effect. Each TEAE was classified for severity based on the Common Terminology Criteria for Adverse Events version (v) 4.03 and classified for causality in the categories unrelated, unlikely, possible, probable and definitely. TEAEs with causality assessed as possible, probable or definitely were categorised as related to study treatment (treatment-related AEs). TEAEs were coded using the Medical Dictionary for Regulatory Activities (MedDRA) v19.0. Related TEAEs reported in ≥2% of subjects by Preferred Term (PT) are reported by subject.
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End point type |
Primary
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End point timeframe |
From first infusion until 90 days following the final visit dose for each subject. Mean (standard deviation) individual exposure to study treatment was 5.5 (1.96) years.
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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: No primary endpoint was defined for the trial. Evaluation of safety was a main objective. Therefore, the number of subjects with treatment-related TEAEs has been reported as a primary endpoint. |
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| Notes [2] - All subjects were included in the Safety Population. |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||
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End point title |
Change from baseline in eGFR | ||||||||
End point description |
The eGFR was calculated based on serum creatinine values, according to the Chronic Kidney Disease - Epidemiology Collaboration (CKD-EPI) formula (2009).
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End point type |
Secondary
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End point timeframe |
Change from baseline (last assessment prior to first infusion) to last observation (last non-missing assessment for a subject). Mean (standard deviation) duration of treatment at the last observation: 5.4 (2.03) years.
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| Notes [3] - All subjects were included in the Intention-to-treat (ITT Population) |
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| No statistical analyses for this end point | |||||||||
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End point title |
Annualised eGFR slope | ||||||||
End point description |
The annualised eGFR slope was added in the statistical analysis plan. Individual eGFR slopes were derived for each subject using a linear regression model and summarised descriptively.
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End point type |
Secondary
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End point timeframe |
From first infusion until the end of the study; mean (standard deviation) individual duration of exposure was 5.5 (1.96) years.
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| Notes [4] - All subjects were included in the ITT Population. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Shift from baseline UPCR category <0.15 g/g at last scheduled visit | ||||||||||||||
End point description |
At baseline, subjects were categorised by UPCR. Shifts from baseline UPCR category to UPCR category at the last scheduled visit are presented.
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End point type |
Secondary
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End point timeframe |
Shift from baseline (last assessment before first infusion) UPCR category to the last scheduled visit.
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| Notes [5] - Fifty four subjects had UPCR <0.15 g/g at baseline. |
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| No statistical analyses for this end point | |||||||||||||||
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End point title |
Shift from baseline UPCR category ≥0.15 - ≤0.5 g/g at the last scheduled visit | ||||||||||||||
End point description |
At baseline, subjects were categorised by UPCR. Shifts from baseline UPCR category to UPCR category at the last scheduled visit are presented.
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End point type |
Secondary
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End point timeframe |
Shift from baseline (last assessment before first infusion) UPCR category to the last scheduled visit.
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| Notes [6] - Twenty-one subjects had UPCR ≥0.15 - ≤0.5 g/g at baseline. |
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| No statistical analyses for this end point | |||||||||||||||
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End point title |
Shift from baseline UPCR category >0.5 - <1 g/g at last scheduled visit | ||||||||||||||
End point description |
At baseline, subjects were categorised by UPCR. Shifts from baseline UPCR category to UPCR category at the last scheduled visit are presented.
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End point type |
Secondary
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End point timeframe |
Shift from baseline (last assessment before first infusion) UPCR category to the last scheduled visit.
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| Notes [7] - Eleven subjects had UPCR category >0.5 - <1 g/g at baseline. |
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| No statistical analyses for this end point | |||||||||||||||
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End point title |
Shift from baseline UPCR category ≥1 g/g at the last scheduled visit | ||||||||||||||
End point description |
At baseline, subjects were categorised by UPCR. Shifts from baseline UPCR category to UPCR category at the last scheduled visit are presented.
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End point type |
Secondary
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End point timeframe |
Shift from baseline (last assessment before first infusion) UPCR category to the last scheduled visit.
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| Notes [8] - Eleven subjects had UPCR ≥1 g/g at baseline. |
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| No statistical analyses for this end point | |||||||||||||||
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End point title |
Change from baseline in biomarkers for Fabry disease | ||||||||||||
End point description |
Plasma Lyso-Gb3 was assessed in different laboratories in studies PB-102-F01/F02/F03 and studies PB-102-F20/F30 and CLI-06657AA1-04. Plasma Gb3 was assessed in a different unit in studies PB-102-F01/F02/F03 and study CLI-06657AA1-04 and conversion between the units was not possible. Therefore, analyses of changes from baseline were performed in the pooled sample of participants enrolled from studies PB-102-F20 and PB-102-F30 (87 participants).
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End point type |
Secondary
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End point timeframe |
Change from baseline (last assessment prior to first infusion) to last observation (last non-missing assessment for each subject). Mean (standard deviation) duration of treatment at last observation for Lyso-Gb3/Gb3: 5.0 (1.65)/5.0 (1.68) years.
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Change from baseline for short form BPI pain severity items | ||||||||||||||||
End point description |
The short form BPI consists of four pain severity items (pain at its worst, pain at its least, pain on the average and pain right now) and seven pain interference items (general activity, mood, walking ability, normal work, relations with other people, sleep and enjoyment of life) assessed over a 24-hour recall period. Each item is rated on a scale from 0 (no pain/interference) to 10 (worst pain imaginable/complete interference). Subjects report percentage of pain relief by analgesics over the past 24 hours as well.
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End point type |
Secondary
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End point timeframe |
Change from baseline (last assessment prior to first infusion) to last observation (last non-missing assessment for each subject) for the pain severity items. Mean (standard deviation) duration of treatment at the last observation: 5.4 (2.02) years.
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| Notes [9] - All subjects were included in the ITT Population. |
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| No statistical analyses for this end point | |||||||||||||||||
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End point title |
Change from baseline for the Mainz Severity Score Index (MSSI) overall score | ||||||||
End point description |
The MSSI represents patients with Fabry disease and comprises four domains covering general, neurological, cardiovascular and renal signs and symptoms. Overall scores (i.e. the sum of domain scores) of <20, ≥20 - ≤40 and >40 indicate mild, moderate and severe disease, respectively. An increase in the score indicates increased severity of disease.
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End point type |
Secondary
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End point timeframe |
Change from baseline (last assessment prior to first infusion) to last observation (last non-missing assessment for the subject) in overall score. Mean (standard deviation) duration of treatment at the last observation: 5.3 (2.04) years.
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| Notes [10] - All subjects were included in the ITT Population. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Shift from baseline for subjects using no pain medication at baseline | ||||||||||||
End point description |
At baseline, subjects were categorised by the number of pain medications used (0, 1 and 2+ pain medications). Shifts from baseline to 72 months in the number of subjects using pain medications (categorised by number of pain medications used) are presented. Forty subjects used no pain medication at baseline. Of these, data were available for 21 subjects at 72 months.
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End point type |
Secondary
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End point timeframe |
Shift from baseline (last assessment prior to first infusion) to 72 months in number of subjects using no pain medication at baseline.
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| Notes [11] - Forty subjects used no pain medications at baseline. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Shift from baseline for subjects using 1 pain medication at baseline | ||||||||||||
End point description |
At baseline, subjects were categorised by the number of pain medications used (0, 1 and 2+ pain medications). Shifts from baseline to 72 months in the number of subjects using pain medications (categorised by number of pain medications used) are presented. Thirty-one subjects used 1 pain medication at baseline. Of these, 17 subjects had data available at 72 months.
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End point type |
Secondary
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End point timeframe |
Shift from baseline (last assessment prior to first infusion) to 72 months in number of subjects using 1 pain medication at baseline.
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| Notes [12] - Thirty-one subjects used 1 pain medication at baseline. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Shift from baseline for subjects using 2+ pain medications at baseline | ||||||||||||
End point description |
At baseline, subjects were categorised by the number of pain medications used (0, 1 and 2+ pain medications). Shifts from baseline to 72 months in the number of subjects using pain medications (categorised by number of pain medications used) are presented. Twenty-six subjects used 2+ pain medications at baseline. Of these, 9 subjects had data available at 72 months.
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End point type |
Secondary
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End point timeframe |
Shift from baseline (last assessment prior to first infusion) to 72 months in number of subjects using 2+ pain medications at baseline.
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| Notes [13] - Twenty-six subjects used 2+ pain medications at baseline. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Change from baseline for QoL assessment | ||||||||
End point description |
Quality of life was assessed by administering the EQ-5D-5L questionnaire. This consists of the EuroQoL 5 Dimensions (EQ-5D) descriptive system and the EuroQoL visual analogue scale (EQ VAS). For the EQ VAS, subjects rated their current health on a vertical VAS which has endpoints labelled 'the best health you can imagine' (score of 100) and 'the worst health you can imagine' (score of 0). An increase in score indicates worsening.
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End point type |
Secondary
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End point timeframe |
Change from baseline (last assessment prior to first infusion) to last observation (last non-missing assessment for the subject) for the EQ VAS. Mean (standard deviation) duration of treatment at the last observation was 5.0 (1.65) years.
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| No statistical analyses for this end point | |||||||||
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End point title |
Change from baseline for left ventricular mass index (LVMI) assessed by cardiac magnetic resonance imaging (MRI) | ||||||||||||
End point description |
The LVMI with and without hypertrophy was assessed by cardiac MRI.
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End point type |
Secondary
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End point timeframe |
Change from baseline (last assessment prior to first infusion) to last observation (last non-missing assessment for the subject). Mean duration of treatment at last observation for LVMI with/without hypertrophy:4.5/5.1 years.
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| Notes [14] - All subjects were included in the ITT Population. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Number of subjects who had ADA at any post-baseline visit | ||||||
End point description |
The ADA status was assessed as per the schedule of assessments based on sequential evaluation. The subject was considered ADA-positive if IgG screening was presumptive positive and subsequent IgG immunodepletion was positive.
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End point type |
Secondary
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End point timeframe |
From first infusion until the end of the study: mean (standard deviation) individual duration of treatment was 5.5 (1.96) years.
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| Notes [15] - All subjects were included in the Safety Population. |
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| No statistical analyses for this end point | |||||||
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End point title |
Number of subjects with treatment-emergent ADA who had titre-boosted or treatment-induced ADA | ||||||||||
End point description |
The ADA status at a visit was decided based on a sequential evaluation as per the schedule of assessments. If the IgG screening was negative, the subject was ADA-negative at that visit. If the IgG screening was presumptive positive, an IgG immunodepletion test was performed and the subject was considered ADA-positive or -negative at the visit based on whether the test was positive or negative. Baseline was the last assessment before the first infusion of pegunigalsidase alfa. Subjects were considered to be treatment-emergent ADA-positive if they had titre-boosted or treatment-induced ADA. The ADA were titre-boosted if subjects were ADA-positive at baseline and ADA titre had increased by at least 4-fold from baseline during treatment. The ADA were treatment-induced if subjects were ADA-negative at baseline and ADA-positive in at least one timepoint post-first infusion.
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End point type |
Secondary
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End point timeframe |
From first infusion until the end of the study: mean (standard deviation) individual duration of treatment was 5.5 (1.96) years.
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| Notes [16] - Thirty-one subjects had treatment-emergent ADA. |
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| No statistical analyses for this end point | |||||||||||
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End point title |
Shift from baseline for subjects using 0 infusion premedication at baseline | ||||||||||||||||||||||||||||||||||||||
End point description |
Infusion premedications were not collected in studies PB-102-F01/F02/F03. Infusion premedications were analysed as a safety endpoint in the Safety Population excluding Cohort F03. Subjects were categorised according to number of infusion premedications used (0, 1, 2 and 3+) at baseline and subsequent time points. Shifts from baseline to Months 12, 24, 48 and 72 are presented for subjects with no infusion premedication use at baseline.
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End point type |
Secondary
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End point timeframe |
Shift from baseline to Months 12, 24, 48 and 72.
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| Notes [17] - A total of 65 subjects used 0 infusion premedication at baseline. |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||
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End point title |
Shift from baseline for subjects using 1 infusion premedication at baseline | ||||||||||||||||||||||||||||||||||||||
End point description |
Infusion premedications were not collected in studies PB-102-F01/F02/F03. Infusion premedications were analysed as a safety endpoint in the Safety Population excluding Cohort F03. Subjects were categorised according to number of infusion premedications used (0, 1, 2 and 3+) at baseline and subsequent time points. Shifts from baseline to Months 12, 24, 48 and 72 are presented for subjects using 1 infusion premedication at baseline (first infusion).
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End point type |
Secondary
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End point timeframe |
Shift from baseline to Months 12, 24, 48 and 72.
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| Notes [18] - A total of 9 subjects used 1 infusion premedication at baseline. |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||
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End point title |
Shift from baseline for subjects using 2 infusion premedications at baseline | ||||||||||||||||||||||||||||||||||||||
End point description |
Infusion premedications were not collected in studies PB-102-F01/F02/F03. Infusion premedications were analysed as a safety endpoint in the Safety Population excluding Cohort F03. Subjects were categorised according to number of infusion premedications used (0, 1, 2 and 3+) at baseline and subsequent time points. Shifts from baseline to Months 12, 24, 48 and 72 are presented for subjects using 2 infusion premedications at baseline (first infusion).
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End point type |
Secondary
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End point timeframe |
Shift from baseline to Months 12, 24, 48 and 72.
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| Notes [19] - A total of 8 subjects used 2 infusion premedications at baseline. |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||
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End point title |
Shift from baseline for subjects using 3+ infusion premedications at baseline | ||||||||||||||||||||||||||||||||||||||
End point description |
Infusion premedications were not collected in studies PB-102-F01/F02/F03. Infusion premedications were analysed as a safety endpoint in the Safety Population excluding Cohort F03. Subjects were categorised according to number of infusion premedications used (0, 1, 2 and 3+) at baseline and subsequent time points. Shifts from baseline to Months 12, 24, 48 and 72 are presented for subjects using 3+ infusion premedications at baseline (first infusion).
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End point type |
Secondary
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End point timeframe |
Shifts from baseline to Months 12, 24, 48 and 72.
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| Notes [20] - A total of 5 subjects used 3+ infusion premedications at baseline. |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||
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End point title |
Number of subjects with infusion-related reactions (IRRs) during infusion or within 2 hours after its completion (IRR-2H) | ||||||||||||||||||||||
End point description |
An IRR was defined as a reaction to the infusion of pharmacological and/or biological substances; symptoms could appear within minutes to 2 hours following the end of the infusion and could include pruritus, flushing, swelling, dyspnoea, bronchospasm and hypotension. IRRs could be evaluated up to 24 hours from occurrence. Two time frames were considered for IRR analysis: IRR-2H and IRRs occurring during the infusion or within 24 hours after its completion (IRR-24H). All IRR-2H were also classified as IRR-24H. IRR-2H reported for >1 subject overall by MedDRA PT are presented by subject. A total of 23 subjects experienced 67 IRR-2H.
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End point type |
Secondary
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End point timeframe |
From the first infusion of pegunigalsidase alfa until the last infusion for each subject. Mean (standard deviation) duration of exposure was 5.5 (1.96) years.
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| Notes [21] - All subjects were included in the Safety Population. |
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| No statistical analyses for this end point | |||||||||||||||||||||||
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End point title |
Number of subjects with IRRs during infusion or within 24 hours after its completion (IRR-24H) | ||||||||||||||||||||||||||||
End point description |
An IRR was defined as a reaction to the infusion of pharmacological and/or biological substances; symptoms could appear within minutes to 2 hours following the end of the infusion and could include pruritus, flushing, swelling, dyspnoea, bronchospasm and hypotension. IRRs could be evaluated up to 24 hours from occurrence. Two time frames were considered for IRR analysis: IRR-2H and IRR-24H. All IRR-2H were also classified as IRR-24H. IRR-24H reported for >1 subject overall by MedDRA PT are presented by subject. A total of 29 subjects experienced 83 IRR-24H.
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End point type |
Secondary
|
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End point timeframe |
From the first infusion of pegunigalsidase alfa until the last infusion for each subject. Mean (standard deviation) duration of exposure was 5.5 (1.96) years.
|
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| Notes [22] - All subjects were included in the Safety Population. |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Adverse events were collected from the first ever infusion of pegunigalsidase alfa until 90 days following the final visit dose for each subject.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
19.0
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Reporting groups
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Reporting group title |
Overall population
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Reporting group description |
All subjects received pegunigalsidase alfa 1 mg/kg by intravenous infusion every 2 weeks | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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06 Nov 2018 |
This amendment resulted in Protocol version 2.0 dated 17 July 2018. The duration of treatment was changed from 'no less than 24 months and up to 48 months' to 'up to 48 months'. Appendix 3 of the protocol was adapted and subjects with progressive or severe hypersensitivity were to be withdrawn from the study only if not allayed with pre-treatment. A visit for dose adjustment according to the subject's weight was removed. Flow charts and visits were adapted as intervals between sampling timepoints for some efficacy assessments and ADA assessments were increased to ease subject burden. Plasma Gb3 and Lyso-Gb3 concentrations were removed from the list of efficacy variables. The timing of vital sign evaluations was changed to every 30 min during the first hour of infusion and then every 60 min for subjects who tolerated the infusion, to reduce subject burden without compromising subject safety. |
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28 Feb 2020 |
This amendment resulted in Protocol version 4.0 dated 25 September 2019. Safety-related content was updated in the introduction. Visits were added for dose adjustment according to the subject's weight. GalafoldTM was added as a prohibited concomitant medication. Assessment of plasma Gb3 concentrations was added as an efficacy assessment and it was specified that the clinical events mentioned in the endpoint in the synopsis referred to Fabry clinical events. The intervals between sampling timepoints for some efficacy assessments were decreased and more frequent assessments were included for subjects enrolled from study PB-102-F20. Intervals between sampling timepoints for ADA assessments were decreased and more frequent assessments were included for subjects enrolled from study PB-102-F20. Screening assessments of serum creatinine and cystatin C and of QoL were added for subjects enrolled from study PB-102-F03. Accordingly, flow charts and visits were modified. Creatine was replaced with creatine phosphokinase in biochemistry assessments and assessment of nitrite and leukocytes was included in urinalysis. The number of follow-up calls for subjects in the Home Care programme was reduced. |
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15 Oct 2021 |
This amendment resulted in Protocol version 5.0 dated 29 June 2021. Safety-related content was updated. The duration of treatment was changed from 'up to 48 months' to 'up to 60 months'. Further dose adjustment visits were planned. In the safety assessments, instructions were included regarding continuation of assessments of serum creatinine and cystatin C in case of end-stage renal disease. A more specific definition of acute kidney injury was included. Instructions were included regarding reporting and follow-up of pregnancies. The flow chart was updated. In the appendices, cardiac MRI parameters were specified and Appendix 9 on chronic kidney disease stages was added. In the statistical analysis section of the protocol, text was added on the statistical analysis plan, study PB-102-F03 was reflected in the sample size wording and analysis specifications were added. Instructions were added regarding postponing visits planned to study PB-102-F20 to study CLI-06657AA1-04 during the coronavirus disease (COVID-19) pandemic. |
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09 Dec 2022 |
This amendment resulted in Protocol version 6.0 dated 25 April 2022. Sponsor’s Medical Expert (details) replaced the Medical Monitor. The protocol number was changed from PB-102-F60 to CLI-06657AA1-04. Sponsor was changed from Protalix Ltd to Chiesi and Sponsor/details were updated. Contraception needs were clarified and pregnancy management was updated as per Chiesi requirements. Inclusion criterion 6.3.1 was modified (enrolment had been completed). The need for Sponsor approval for changes in infusion time according to subject’s weight pending subject tolerability and Investigator evaluation was deleted as the Sponsor was consulted but not responsible for the action/decision. It was further clarified that the study treatment could be permanently discontinued at Sponsor’s discretion based on safety concerns, potential major protocol violation and/or fraud. It was specified that CTCAE Version 4.03, 2010 would be used to define grade toxicity. Sections of the synopsis were updated as applicable. The exclusion criteria specified that subjects could be excluded from the study as per the Investigator’s judgement (earlier, Investigator’s and Medical Monitor’s judgement). Study results from the PRX-102 programme were deleted as complete information was included in the Investigator's Brochure. A risk/benefit assessment was added. Duration of treatment was updated (to ‘until pegunigalsidase alfa was commercially available to the subject or at the Sponsor’s discretion’ and end of study and last visit were defined accordingly. Additional visits were included for dose adjustment. Only the Investigator's decision was sufficient for subjects to receive home infusions; Sponsor's Medical Expert was to be notified. Study flow chart was built up to include up to Visit 209. Urine pregnancy test was added (for females of childbearing potential). Schedule of MSSSI assessments was updated, infusion-related reactions were defined. Definition of the ITT Population was modified. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
