Trial Outcomes & Findings for Safety and Efficacy of PRX-102 in Patients With Fabry Disease Currently Treated With REPLAGAL® (Agalsidase Alfa) (NCT NCT03018730)
NCT ID: NCT03018730
Last Updated: 2023-09-13
Results Overview
Results represent the number of treatment-emergent adverse events (TEAE) that were considered possibly, probably, or definitely related to treatment
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
22 participants
Primary outcome timeframe
12 months
Results posted on
2023-09-13
Participant Flow
A total of 22 adult patients were planned to be included in the study; no more than 25% were planned to be female patients. In practice, 15 males and 7 females (32%) received treatment in this study; 20 patients (13 males and 7 females) completed the 12 month treatment duration.
Participant milestones
| Measure |
PRX-102
PRX-102 (pegunigalsidase alfa): PRX-102 infusion 1 mg/kg every 2 weeks
|
|---|---|
|
Overall Study
STARTED
|
22
|
|
Overall Study
COMPLETED
|
20
|
|
Overall Study
NOT COMPLETED
|
2
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Safety and Efficacy of PRX-102 in Patients With Fabry Disease Currently Treated With REPLAGAL® (Agalsidase Alfa)
Baseline characteristics by cohort
| Measure |
PRX-102
n=22 Participants
PRX-102 infusion 1 mg/kg every 2 weeks
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
22 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
|
Age, Continuous
|
44.0 years
STANDARD_DEVIATION 11.0 • n=5 Participants
|
|
Sex: Female, Male
Female
|
7 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
15 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Race · American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Race · Asian
|
0 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Race · Black or African American
|
0 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Race · Native Hawaiian or other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Race · White
|
22 Participants
n=5 Participants
|
|
Region of Enrollment
Canada
|
2 participants
n=5 Participants
|
|
Region of Enrollment
Netherlands
|
1 participants
n=5 Participants
|
|
Region of Enrollment
Czechia
|
8 participants
n=5 Participants
|
|
Region of Enrollment
Norway
|
2 participants
n=5 Participants
|
|
Region of Enrollment
United Kingdom
|
6 participants
n=5 Participants
|
|
Region of Enrollment
Slovenia
|
1 participants
n=5 Participants
|
|
Region of Enrollment
Australia
|
2 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 12 monthsResults represent the number of treatment-emergent adverse events (TEAE) that were considered possibly, probably, or definitely related to treatment
Outcome measures
| Measure |
PRX-102
n=22 Participants
PRX-102 infusion 1 mg/kg every 2 weeks
|
PRX-102 Male
PRX-102 infusion 1 mg/kg every 2 weeks
|
PRX-102 Female
PRX-102 infusion 1 mg/kg every 2 weeks
|
|---|---|---|---|
|
Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.03
At least 1 TEAE
|
21 participants
|
—
|
—
|
|
Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.03
At least 1 mild or moderate TEAE
|
19 participants
|
—
|
—
|
|
Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.03
At least 1 severe TEAE
|
4 participants
|
—
|
—
|
|
Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.03
At least 1 SAE
|
4 participants
|
—
|
—
|
|
Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.03
At least 1 TEAE unrelated or unlikely related
|
19 participants
|
—
|
—
|
|
Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.03
At least 1 TEAE related to study treatment
|
5 participants
|
—
|
—
|
|
Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.03
At least 1 SAE related to study treatment
|
2 participants
|
—
|
—
|
|
Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.03
At least 1 TEAE leading to discontinuation
|
2 participants
|
—
|
—
|
|
Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.03
At least 1 TEAE leading to death
|
0 participants
|
—
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline and Month 12 (week 52)eGFR was calculated based on the serum creatinine values that were assessed at weeks 4, 8, 12, 16, 20, 26, 30, 34, 38, 42, 46, 52 according to the CKD-EPI formula, baseline and Month 12 (week 52) reported. The absolute change in eGFR from baseline measurement at visit 1 prior to first PRX-102 infusion to last measurement at Month 12 was summarized using descriptive statistics.
Outcome measures
| Measure |
PRX-102
n=20 Participants
PRX-102 infusion 1 mg/kg every 2 weeks
|
PRX-102 Male
n=13 Participants
PRX-102 infusion 1 mg/kg every 2 weeks
|
PRX-102 Female
n=7 Participants
PRX-102 infusion 1 mg/kg every 2 weeks
|
|---|---|---|---|
|
eGFR
Baseline eGFR
|
79.46 mL/min/1.73m^2
Standard Error 4.92
|
75.87 mL/min/1.73m^2
Standard Error 6.62
|
86.14 mL/min/1.73m^2
Standard Error 6.72
|
|
eGFR
Month 12 (week 52) eGFR
|
76.91 mL/min/1.73m^2
Standard Error 5.22
|
74.27 mL/min/1.73m^2
Standard Error 7.15
|
81.80 mL/min/1.73m^2
Standard Error 7.09
|
|
eGFR
Change in eGFR from Baseline to Month 12 (week 52)
|
-2.56 mL/min/1.73m^2
Standard Error 2.14
|
-1.60 mL/min/1.73m^2
Standard Error 2.75
|
-4.34 mL/min/1.73m^2
Standard Error 3.54
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Pre-switch, Post-switchThe annualized change in eGFR (slope) per patient was calculated with all available eGFR values using a linear regression. The mean pre-switch slope is the eGFR slope during screening period and pre-infusion visit 1 (while on Replagal®). The mean post-switch slope is the eGFR slope during PRX-102 treatment, calculated based on eGFR vales at weeks 4, 8, 12, 16, 20, 26, 30, 34, 38, 42, 46, 52 after visit 1. The mean change in eGFR slope from pre- to post-switch is the mean difference between the two slopes. eGFR was calculated based on the serum creatinine values according to the CKD-EPI formula.
Outcome measures
| Measure |
PRX-102
n=20 Participants
PRX-102 infusion 1 mg/kg every 2 weeks
|
PRX-102 Male
n=13 Participants
PRX-102 infusion 1 mg/kg every 2 weeks
|
PRX-102 Female
n=7 Participants
PRX-102 infusion 1 mg/kg every 2 weeks
|
|---|---|---|---|
|
Mean Annualised Change in eGFR (Slope)
pre-switch
|
-5.9 mL/min/1.73m^2/year
Standard Error 1.34
|
-6.36 mL/min/1.73m^2/year
Standard Error 1.89
|
-5.03 mL/min/1.73m^2/year
Standard Error 1.65
|
|
Mean Annualised Change in eGFR (Slope)
post-switch
|
-1.19 mL/min/1.73m^2/year
Standard Error 1.77
|
-1.73 mL/min/1.73m^2/year
Standard Error 2.64
|
-0.21 mL/min/1.73m^2/year
Standard Error 1.47
|
|
Mean Annualised Change in eGFR (Slope)
Change in eGFR slope from pre- to post-switch
|
4.70 mL/min/1.73m^2/year
Standard Error 2.26
|
4.63 mL/min/1.73m^2/year
Standard Error 3.48
|
4.83 mL/min/1.73m^2/year
Standard Error 1.09
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline and month 12 (week 52)Plasma Lyso-Gb3 is Fabry disease specific biomarker that can assess treatment outcome which was measured at Baseline and weeks 12, 26, 38, 52. Baseline and Month 12 (week 52) reported.
Outcome measures
| Measure |
PRX-102
n=20 Participants
PRX-102 infusion 1 mg/kg every 2 weeks
|
PRX-102 Male
n=13 Participants
PRX-102 infusion 1 mg/kg every 2 weeks
|
PRX-102 Female
n=7 Participants
PRX-102 infusion 1 mg/kg every 2 weeks
|
|---|---|---|---|
|
Plasma Lyso-Gb3
Baseline
|
38.51 nM
Standard Error 9.68
|
51.81 nM
Standard Error 13.60
|
13.81 nM
Standard Error 2.31
|
|
Plasma Lyso-Gb3
Month 12 (Week 52)
|
24.20 nM
Standard Error 5.10
|
32.25 nM
Standard Error 6.89
|
9.24 nM
Standard Error 1.08
|
|
Plasma Lyso-Gb3
Change from Baseline
|
-14.31 nM
Standard Error 5.13
|
-19.55 nM
Standard Error 7.55
|
-4.57 nM
Standard Error 1.42
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 12 monthsUrine Protein to Creatinine Ratio (UPCR), assessed by spot urine test, at Month 12 (Week 52).Number of Participants According to Protein/Creatinine Ratio (UPCR) level
Outcome measures
| Measure |
PRX-102
n=20 Participants
PRX-102 infusion 1 mg/kg every 2 weeks
|
PRX-102 Male
n=13 Participants
PRX-102 infusion 1 mg/kg every 2 weeks
|
PRX-102 Female
n=7 Participants
PRX-102 infusion 1 mg/kg every 2 weeks
|
|---|---|---|---|
|
Number of Participants According to Protein/Creatinine Ratio (UPCR)
Severely increased
|
5 Subjects
|
4 Subjects
|
1 Subjects
|
|
Number of Participants According to Protein/Creatinine Ratio (UPCR)
Protein Undetectable
|
9 Subjects
|
7 Subjects
|
2 Subjects
|
|
Number of Participants According to Protein/Creatinine Ratio (UPCR)
Normal to Mildly increased
|
4 Subjects
|
2 Subjects
|
2 Subjects
|
|
Number of Participants According to Protein/Creatinine Ratio (UPCR)
Moderately increased
|
2 Subjects
|
0 Subjects
|
2 Subjects
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 12 monthsLeft ventricular mass was determined based on cardiac MRI data and the LVMI was indexed to patient's body surface area (g/m\^2). In male patients the normal range for LVMI was 57-91 g/m\^2, in female patients 47-77 g/m\^2.
Outcome measures
| Measure |
PRX-102
n=20 Participants
PRX-102 infusion 1 mg/kg every 2 weeks
|
PRX-102 Male
n=13 Participants
PRX-102 infusion 1 mg/kg every 2 weeks
|
PRX-102 Female
n=7 Participants
PRX-102 infusion 1 mg/kg every 2 weeks
|
|---|---|---|---|
|
Left Ventricular Mass Index (g/m^2) by MRI
Baseline
|
86.9 g/m^2
Standard Error 6.9
|
97.6 g/m^2
Standard Error 8.9
|
66.9 g/m^2
Standard Error 5.8
|
|
Left Ventricular Mass Index (g/m^2) by MRI
Month 12 (Week 52)
|
89.4 g/m^2
Standard Error 6.1
|
98.3 g/m^2
Standard Error 7.8
|
74.1 g/m^2
Standard Error 7.2
|
|
Left Ventricular Mass Index (g/m^2) by MRI
Change from Baseline
|
4.1 g/m^2
Standard Error 2.8
|
2.4 g/m^2
Standard Error 3.4
|
7.1 g/m^2
Standard Error 5.0
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 12 monthsThe EQ VAS, of the EQ 5D 5L questionnaire, records the subject's self-rated health on a vertical, visual analogue scale where the endpoints are labelled 'Best imaginable health state' (score "100") and 'Worst imaginable health state' (score "0").
Outcome measures
| Measure |
PRX-102
n=20 Participants
PRX-102 infusion 1 mg/kg every 2 weeks
|
PRX-102 Male
n=13 Participants
PRX-102 infusion 1 mg/kg every 2 weeks
|
PRX-102 Female
n=7 Participants
PRX-102 infusion 1 mg/kg every 2 weeks
|
|---|---|---|---|
|
Quality of Life EQ VAS
Baseline
|
71.8 Score
Standard Error 4.3
|
66.8 Score
Standard Error 5.3
|
81.6 Score
Standard Error 6.1
|
|
Quality of Life EQ VAS
Month 12
|
76.9 Score
Standard Error 4.5
|
71.5 Score
Standard Error 5.4
|
86.7 Score
Standard Error 7.0
|
|
Quality of Life EQ VAS
Change from Baseline
|
5.1 Score
Standard Error 3.3
|
4.8 Score
Standard Error 4.9
|
5.6 Score
Standard Error 3.0
|
Adverse Events
All Patients
Serious events: 4 serious events
Other events: 21 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
All Patients
n=22 participants at risk
PRX-102 infusion 1 mg/kg every 2 weeks
|
|---|---|
|
Immune system disorders
Type I hypersensitivity
|
9.1%
2/22 • 12 months
|
|
Infections and infestations
Infectious mononucleosis
|
4.5%
1/22 • 12 months
|
|
Infections and infestations
Urinary tract infection
|
4.5%
1/22 • 12 months
|
Other adverse events
| Measure |
All Patients
n=22 participants at risk
PRX-102 infusion 1 mg/kg every 2 weeks
|
|---|---|
|
Injury, poisoning and procedural complications
Contusion
|
9.1%
2/22 • Number of events 2 • 12 months
|
|
Injury, poisoning and procedural complications
Infusion related reaction
|
9.1%
2/22 • Number of events 3 • 12 months
|
|
Cardiac disorders
Palpitations
|
9.1%
2/22 • Number of events 2 • 12 months
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
13.6%
3/22 • Number of events 3 • 12 months
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
9.1%
2/22 • Number of events 3 • 12 months
|
|
Immune system disorders
Type 1 hypersensitivity
|
9.1%
2/22 • Number of events 2 • 12 months
|
|
Nervous system disorders
Headache
|
22.7%
5/22 • Number of events 5 • 12 months
|
|
Nervous system disorders
Dizziness
|
9.1%
2/22 • Number of events 8 • 12 months
|
|
General disorders
Fatigue
|
9.1%
2/22 • Number of events 2 • 12 months
|
|
Gastrointestinal disorders
Gastroesophageal reflux disease
|
9.1%
2/22 • Number of events 2 • 12 months
|
|
Gastrointestinal disorders
Toothache
|
9.1%
2/22 • Number of events 2 • 12 months
|
|
Skin and subcutaneous tissue disorders
Rash pruritic
|
9.1%
2/22 • Number of events 2 • 12 months
|
|
Skin and subcutaneous tissue disorders
Erythema
|
9.1%
2/22 • Number of events 2 • 12 months
|
|
Skin and subcutaneous tissue disorders
Rash
|
9.1%
2/22 • Number of events 2 • 12 months
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
9.1%
2/22 • Number of events 2 • 12 months
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
9.1%
2/22 • Number of events 2 • 12 months
|
|
Infections and infestations
Nasopharyngitis
|
31.8%
7/22 • Number of events 9 • 12 months
|
|
Infections and infestations
Lower respiratory tract infection
|
9.1%
2/22 • Number of events 2 • 12 months
|
|
Infections and infestations
Upper respiratory tract infection
|
9.1%
2/22 • Number of events 2 • 12 months
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The clinical trial agreement that is generally provided to the sites and Investigators contains a Publication paragraph that indicates the following: shall not, without the Sponsor's prior written consent, independently publish, present or otherwise disclose any results of or information pertaining to the trial until a multi-center publication is published, subject to certain limitations regarding timing and the confidentiality of unpublished data.
- Publication restrictions are in place
Restriction type: OTHER