Trial Outcomes & Findings for Study of the Safety and Efficacy of PRX-102 Compared to Agalsidase Beta on Renal Function (NCT NCT02795676)

NCT ID: NCT02795676

Last Updated: 2023-09-13

Results Overview

The individual annualized mean change (slope) in eGFR (mL/min/1.73 m\^2/year) is an estimate of the individual patient's annualized change in eGFR, which is derived from the eGFR assessments over time, for up to 24 months. The individual annualized mean change (slope) in eGFR is estimated for each patient with at least 4 eGFR observations. For patients with fewer than 4 eGFR observations, the slope will be missing.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 78 participants
• Primary outcome timeframe: 24 months
• Results posted on: 2023-09-13

Participant Flow

Symptomatic adult Fabry patients who had been taking agalsidase beta for at least 1 year and on a stable dose for at least 6 months. No more than 50% could be female. Screening eGFR (CKD-EPI) 40 to 120 mL/min/1.73 m^2; Screening linear eGFR slope more negative than -2 mL/min/1.73 m^2/year based on at least 3 values over ~1 year.

Of the 78 randomized patients, 53 were assigned to the PRX-102 arm and 25 to the agalsidase beta arm. One PRX-102 patient withdrew consent before receiving the study product; accordingly, 77 patients were treated, 52 in the PRX-102 arm and 25 in the agalsidase beta arm.

Participant milestones

Measure	PRX-102 (Pegunigalsidase Alfa) Pegunigalsidase alfa administered as an intravenous infusion every 2 weeks, at a dosage of 1 mg/kg	Agalsidase Beta Agalsidase beta administered as an intravenous infusion every 2 weeks, at a dosage of 1 mg/kg
Overall Study STARTED	53	25
Overall Study Treated	52	25
Overall Study COMPLETED	48	24
Overall Study NOT COMPLETED	5	1

Reasons for withdrawal

Measure	PRX-102 (Pegunigalsidase Alfa) Pegunigalsidase alfa administered as an intravenous infusion every 2 weeks, at a dosage of 1 mg/kg	Agalsidase Beta Agalsidase beta administered as an intravenous infusion every 2 weeks, at a dosage of 1 mg/kg
Overall Study Adverse Event	2	0
Overall Study Withdrawal by Subject	3	1

Baseline Characteristics

Study of the Safety and Efficacy of PRX-102 Compared to Agalsidase Beta on Renal Function

Baseline characteristics by cohort

Measure	PRX-102 (Pegunigalsidase Alfa) n=52 Participants Pegunigalsidase alfa administered as an intravenous infusion every 2 weeks, at a dosage of 1 mg/kg	Agalsidase Beta n=25 Participants Agalsidase beta administered as an intravenous infusion every 2 weeks, at a dosage of 1 mg/kg	Total n=77 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	52 Participants n=5 Participants	25 Participants n=7 Participants	77 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	43.9 years STANDARD_DEVIATION 10.2 • n=5 Participants	45.2 years STANDARD_DEVIATION 9.6 • n=7 Participants	44.3 years STANDARD_DEVIATION 10.0 • n=5 Participants
Sex: Female, Male Female	23 Participants n=5 Participants	7 Participants n=7 Participants	30 Participants n=5 Participants
Sex: Female, Male Male	29 Participants n=5 Participants	18 Participants n=7 Participants	47 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) White	49 Participants n=5 Participants	23 Participants n=7 Participants	72 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment Netherlands	4 Participants n=5 Participants	1 Participants n=7 Participants	5 Participants n=5 Participants
Region of Enrollment Hungary	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment United States	33 Participants n=5 Participants	18 Participants n=7 Participants	51 Participants n=5 Participants
Region of Enrollment Czechia	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment Norway	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Region of Enrollment Finland	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment Italy	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Region of Enrollment United Kingdom	4 Participants n=5 Participants	1 Participants n=7 Participants	5 Participants n=5 Participants
Region of Enrollment Slovenia	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Region of Enrollment France	3 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants
Region of Enrollment Spain	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants

PRIMARY outcome

Timeframe: 24 months

Population: The Intent to Treat (ITT) population includes all randomized patients who received at least one dose of the assigned study medication with at least 4 eGFR observations. For 1 patient with fewer than 4 eGFR observations, the slope was missing.

The individual annualized mean change (slope) in eGFR (mL/min/1.73 m^2/year) is an estimate of the individual patient's annualized change in eGFR, which is derived from the eGFR assessments over time, for up to 24 months.

The individual annualized mean change (slope) in eGFR is estimated for each patient with at least 4 eGFR observations. For patients with fewer than 4 eGFR observations, the slope will be missing.

Outcome measures

Measure	PRX-102 (Pegunigalsidase Alfa) n=51 Participants Pegunigalsidase alfa administered as an intravenous infusion every 2 weeks, at a dosage of 1 mg/kg	Agalsidase Beta n=25 Participants Agalsidase beta administered as an intravenous infusion every 2 weeks, at a dosage of 1 mg/kg
Annualized Change (Slope) in Estimated Glomerular Filtration Rate (eGFR)	-2.514 mL/min/1.73 m^2/year Interval -3.788 to -1.24	-2.155 mL/min/1.73 m^2/year Interval -3.805 to -0.505

SECONDARY outcome

Timeframe: Baseline and Month 24

Population: The Intent to Treat (ITT) population includes all randomized patients who received at least one dose of the assigned study medication.

eGFR was calculated based on measured serum creatinine levels according to the CKD-EPI formula. The median values obtained at baseline and at Month 24 are reported.

The change in eGFR from baseline measurement prior to first infusion to last measurement at Month 24 was summarized using descriptive statistics.

The change was calculated for each subject and the reported value is the median (full range) of these changes.

Outcome measures

Measure	PRX-102 (Pegunigalsidase Alfa) n=52 Participants Pegunigalsidase alfa administered as an intravenous infusion every 2 weeks, at a dosage of 1 mg/kg	Agalsidase Beta n=25 Participants Agalsidase beta administered as an intravenous infusion every 2 weeks, at a dosage of 1 mg/kg
Estimated Glomerular Filtration Rate (eGFR) Baseline	73.45 mL/min/1.73 m^2 Interval 30.2 to 125.9	74.85 mL/min/1.73 m^2 Interval 34.1 to 107.6
Estimated Glomerular Filtration Rate (eGFR) Month 24	69.35 mL/min/1.73 m^2 Interval 27.6 to 113.7	74.48 mL/min/1.73 m^2 Interval 24.4 to 114.8
Estimated Glomerular Filtration Rate (eGFR) Change from Baseline to Month 24	-2.39 mL/min/1.73 m^2 Interval -36.9 to 21.8	-3.20 mL/min/1.73 m^2 Interval -18.0 to 16.8

SECONDARY outcome

Timeframe: Baseline and Month 24

Population: The Intent to Treat (ITT) population includes all randomized patients who received at least one dose of the assigned study medication.

Globotriaosylsphingosine (lyso-Gb3) is a Fabry disease-specific biomarker measured in the plasma. The median concentrations obtained at baseline and at Month 24, and the change from baseline to Month 24 in median concentration, are reported.

The change in Lyso-Gb3 from baseline measurement prior to first infusion to last measurement at Month 24 was summarized using descriptive statistics.

The change was calculated for each subject and the reported value is the median (full range) of these changes.

Outcome measures

Measure	PRX-102 (Pegunigalsidase Alfa) n=52 Participants Pegunigalsidase alfa administered as an intravenous infusion every 2 weeks, at a dosage of 1 mg/kg	Agalsidase Beta n=25 Participants Agalsidase beta administered as an intravenous infusion every 2 weeks, at a dosage of 1 mg/kg
Plasma Lyso-Gb3 Baseline	15.20 nM Interval 0.8 to 143.9	17.60 nM Interval 2.1 to 142.0
Plasma Lyso-Gb3 Month 24	18.80 nM Interval 2.4 to 139.4	15.30 nM Interval 1.5 to 71.2
Plasma Lyso-Gb3 Change from Baseline to Month 24	1.15 nM Interval -32.2 to 32.7	-1.50 nM Interval -102.3 to 2.4

SECONDARY outcome

Timeframe: Baseline and Month 24

Population: The Intent to Treat (ITT) population includes all randomized patients who received at least one dose of the assigned study medication.

The Short Form Brief Pain Inventory ( BPI) questioner is self-completed by patients regarding pain severity and interference.

Descriptive statistics summarize the findings for the change from baseline at Week 104 for "Pain at Its Worst in Last 24 Hours".

The severity of various aspects of pain scored on a scale of 0 to 10 ( no pain / pain as bad as you can imagine).

The change in BPI from baseline measurement prior to first infusion to the last measurement at Month 24 was summarized using descriptive statistics.

The change was calculated for each subject and the reported value is the mean (Standard Error) of these changes.

Outcome measures

Measure	PRX-102 (Pegunigalsidase Alfa) n=52 Participants Pegunigalsidase alfa administered as an intravenous infusion every 2 weeks, at a dosage of 1 mg/kg	Agalsidase Beta n=25 Participants Agalsidase beta administered as an intravenous infusion every 2 weeks, at a dosage of 1 mg/kg
Short Form Brief Pain Inventory (BPI) Baseline	3.5 score on a scale Standard Error 0.4	2.6 score on a scale Standard Error 0.6
Short Form Brief Pain Inventory (BPI) Month 24	3.3 score on a scale Standard Error 0.5	3.0 score on a scale Standard Error 0.7
Short Form Brief Pain Inventory (BPI) Change from Baseline to Month 24	-0.1 score on a scale Standard Error 0.5	0.6 score on a scale Standard Error 0.6

SECONDARY outcome

Timeframe: Baseline and Month 24

Population: The Intent to Treat (ITT) population includes all randomized patients who received at least one dose of the assigned study medication.

The Mainz Severity Score Index (MSSI) is an instrument that is specifically designed to measure the severity of Fabry disease signs/symptoms and to monitor the clinical course of the disease. The MSSI is administered by the investigator, and yields scores for general, neurological, cardiovascular, renal, and overall assessments. The overall score range from 0 to 76. An overall score of less than 20 points is considered mild signs and symptoms of Fabry disease, 20 to 40 is considered moderate, and greater than 40 is considered severe.

The change in overall MSSI score from baseline measurement prior to first infusion to the last measurement at Month 24 was summarized using descriptive statistics.

The change was calculated for each subject and the reported value is the mean (Standard Error) of these changes.

Outcome measures

Measure	PRX-102 (Pegunigalsidase Alfa) n=52 Participants Pegunigalsidase alfa administered as an intravenous infusion every 2 weeks, at a dosage of 1 mg/kg	Agalsidase Beta n=25 Participants Agalsidase beta administered as an intravenous infusion every 2 weeks, at a dosage of 1 mg/kg
Mainz Severity Score Index (MSSI) Baseline	23.18 score on a scale Standard Error 1.42	25.16 score on a scale Standard Error 2.14
Mainz Severity Score Index (MSSI) Month 24	22.11 score on a scale Standard Error 1.80	27.09 score on a scale Standard Error 2.30
Mainz Severity Score Index (MSSI) Change from Baseline to Month 24	-2.07 score on a scale Standard Error 0.77	2.04 score on a scale Standard Error 1.10

SECONDARY outcome

Timeframe: Baseline and Month 24

Population: The Intent to Treat (ITT) population includes all randomized patients who received at least one dose of the assigned study medication.

The UPCR provides an estimate of protein excretion in urine, and is used as an indicator of the extent of chronic kidney disease. It was classified into three categories: 1) UPCR ≤ 0.5 gr/gr, 2) 0.5 gr/gr < UPCR < 1 gr/gr, 3) 1 gr/gr ≤ UPCR. The results are presented as the percentage of patients (%) in each category at baseline and Month 24.

There are no statistical analyses for this endpoint.

Outcome measures

Measure	PRX-102 (Pegunigalsidase Alfa) n=52 Participants Pegunigalsidase alfa administered as an intravenous infusion every 2 weeks, at a dosage of 1 mg/kg	Agalsidase Beta n=25 Participants Agalsidase beta administered as an intravenous infusion every 2 weeks, at a dosage of 1 mg/kg
Urine Protein/Creatinine Ratio (UPCR) UPCR ≤ 0.5 gr/gr, Baseline	69 percentage of participants	80 percentage of participants
Urine Protein/Creatinine Ratio (UPCR) UPCR ≤ 0.5 gr/gr, Month 24	76 percentage of participants	75 percentage of participants
Urine Protein/Creatinine Ratio (UPCR) 0.5 < UPCR < 1 gr/gr, Baseline	17 percentage of participants	8 percentage of participants
Urine Protein/Creatinine Ratio (UPCR) 0.5 < UPCR < 1 gr/gr, Month 24	11 percentage of participants	8 percentage of participants
Urine Protein/Creatinine Ratio (UPCR) UPCR ≥ 1 gr/gr, Baseline	14 percentage of participants	12 percentage of participants
Urine Protein/Creatinine Ratio (UPCR) UPCR ≥ 1 gr/gr, Month 24	13 percentage of participants	17 percentage of participants

SECONDARY outcome

Timeframe: Baseline and Month 24

Population: The Intent to Treat (ITT) population includes all randomized patients who received at least one dose of the assigned study medication. This analysis included the subset of patients in each treatment arm who had hypertrophy at baseline.

Left Ventricular Mass Index (LVMI) based on cardiac MRI for patients with hypertrophy at baseline (for males, hypertrophy is above 91 g/m^2 and for females, above 77 g/m^2).

The change in LVMI from baseline measurement prior to first infusion to the last measurement at Month 24 was summarized using descriptive statistics.

The change was calculated for each subject and the reported value is the median (full range) of these changes.

Outcome measures

Measure	PRX-102 (Pegunigalsidase Alfa) n=12 Participants Pegunigalsidase alfa administered as an intravenous infusion every 2 weeks, at a dosage of 1 mg/kg	Agalsidase Beta n=9 Participants Agalsidase beta administered as an intravenous infusion every 2 weeks, at a dosage of 1 mg/kg
Left Ventricular Mass Index With Hypertrophy at Baseline Baseline	108.005 g/m^2 Interval 81.77 to 168.42	103.030 g/m^2 Interval 78.91 to 147.33
Left Ventricular Mass Index With Hypertrophy at Baseline Month 24	118.130 g/m^2 Interval 87.78 to 150.67	121.380 g/m^2 Interval 63.78 to 187.23
Left Ventricular Mass Index With Hypertrophy at Baseline Change from Baseline to Month 24	-4.790 g/m^2 Interval -24.42 to 21.55	4.120 g/m^2 Interval -28.41 to 41.1

SECONDARY outcome

Timeframe: Baseline and Month 24

Population: The Intent to Treat (ITT) population includes all randomized patients who received at least one dose of the assigned study medication. This analysis included the subset of patients in each treatment arm who did not have hypertrophy at baseline.

Left Ventricular Mass Index (LVMI) based on cardiac MRI for patients without hypertrophy at baseline (for males, hypertrophy is above 91 g/m^2 and for females, above 77 g/m^2).

The change in LVMI from baseline measurement prior to first infusion to the last measurement at Month 24 was summarized using descriptive statistics.

The change was calculated for each subject and the reported value is the median (full range) of these changes.

Outcome measures

Measure	PRX-102 (Pegunigalsidase Alfa) n=28 Participants Pegunigalsidase alfa administered as an intravenous infusion every 2 weeks, at a dosage of 1 mg/kg	Agalsidase Beta n=13 Participants Agalsidase beta administered as an intravenous infusion every 2 weeks, at a dosage of 1 mg/kg
Left Ventricular Mass Index Without Hypertrophy at Baseline Baseline	55.555 g/m^2 Interval 33.81 to 89.24	66.040 g/m^2 Interval 35.74 to 86.92
Left Ventricular Mass Index Without Hypertrophy at Baseline Month 24	52.160 g/m^2 Interval 35.8 to 100.01	62.520 g/m^2 Interval 35.38 to 88.48
Left Ventricular Mass Index Without Hypertrophy at Baseline Change from Baseline to Month 24	1.990 g/m^2 Interval -29.37 to 18.37	0.515 g/m^2 Interval -13.69 to 11.15

Adverse Events

PRX-102 (Pegunigalsidase Alfa)

Serious events: 8 serious events

Other events: 47 other events

Deaths: 0 deaths

Agalsidase Beta

Serious events: 6 serious events

Other events: 24 other events

Deaths: 0 deaths

Serious adverse events

Measure	PRX-102 (Pegunigalsidase Alfa) n=52 participants at risk Pegunigalsidase alfa administered as an intravenous infusion every 2 weeks, at a dosage of 1 mg/kg	Agalsidase Beta n=25 participants at risk Agalsidase beta administered as an intravenous infusion every 2 weeks, at a dosage of 1 mg/kg
Vascular disorders Aortic stenosis	1.9% 1/52 • Number of events 1 • 24 months	0.00% 0/25 • 24 months
Vascular disorders Venous thrombosis limb	1.9% 1/52 • Number of events 1 • 24 months	0.00% 0/25 • 24 months
Surgical and medical procedures Medical device battery replacement	1.9% 1/52 • Number of events 1 • 24 months	0.00% 0/25 • 24 months
Surgical and medical procedures Nephrectomy	1.9% 1/52 • Number of events 1 • 24 months	0.00% 0/25 • 24 months
General disorders Hypothermia	1.9% 1/52 • Number of events 1 • 24 months	0.00% 0/25 • 24 months
General disorders Chest pain	0.00% 0/52 • 24 months	8.0% 2/25 • Number of events 2 • 24 months
Immune system disorders Hypersensitivity	1.9% 1/52 • Number of events 1 • 24 months	0.00% 0/25 • 24 months
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.00% 0/52 • 24 months	4.0% 1/25 • Number of events 1 • 24 months
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.00% 0/52 • 24 months	4.0% 1/25 • Number of events 1 • 24 months
Psychiatric disorders Suicidal ideation	0.00% 0/52 • 24 months	4.0% 1/25 • Number of events 1 • 24 months
Investigations Hepatic enzyme increased	1.9% 1/52 • Number of events 1 • 24 months	0.00% 0/25 • 24 months
Injury, poisoning and procedural complications Contusion	1.9% 1/52 • Number of events 1 • 24 months	0.00% 0/25 • 24 months
Injury, poisoning and procedural complications Femur fracture	1.9% 1/52 • Number of events 1 • 24 months	0.00% 0/25 • 24 months
Cardiac disorders Atrioventricular block second degree	1.9% 1/52 • Number of events 1 • 24 months	0.00% 0/25 • 24 months
Cardiac disorders Atrial fibrillation	0.00% 0/52 • 24 months	4.0% 1/25 • Number of events 1 • 24 months
Cardiac disorders Tachycardia	0.00% 0/52 • 24 months	4.0% 1/25 • Number of events 1 • 24 months
Cardiac disorders Ventricular tachycardia	0.00% 0/52 • 24 months	4.0% 1/25 • Number of events 1 • 24 months
Nervous system disorders Altered state of consciousness	0.00% 0/52 • 24 months	4.0% 1/25 • Number of events 1 • 24 months
Gastrointestinal disorders Protein-losing gastroenteropathy	1.9% 1/52 • Number of events 1 • 24 months	0.00% 0/25 • 24 months
Renal and urinary disorders Acute kidney injury	1.9% 1/52 • Number of events 1 • 24 months	0.00% 0/25 • 24 months
Infections and infestations Bronchitis	1.9% 1/52 • Number of events 1 • 24 months	0.00% 0/25 • 24 months
Infections and infestations Pneumonia	0.00% 0/52 • 24 months	4.0% 1/25 • Number of events 1 • 24 months
Infections and infestations Sepsis	0.00% 0/52 • 24 months	4.0% 1/25 • Number of events 1 • 24 months
Metabolism and nutrition disorders Dehydration	1.9% 1/52 • Number of events 1 • 24 months	0.00% 0/25 • 24 months

Other adverse events

Measure	PRX-102 (Pegunigalsidase Alfa) n=52 participants at risk Pegunigalsidase alfa administered as an intravenous infusion every 2 weeks, at a dosage of 1 mg/kg	Agalsidase Beta n=25 participants at risk Agalsidase beta administered as an intravenous infusion every 2 weeks, at a dosage of 1 mg/kg
Vascular disorders Hypertension	5.8% 3/52 • Number of events 4 • 24 months	4.0% 1/25 • Number of events 1 • 24 months
Vascular disorders Hypotension	0.00% 0/52 • 24 months	8.0% 2/25 • Number of events 2 • 24 months
General disorders Fatigue	17.3% 9/52 • Number of events 10 • 24 months	16.0% 4/25 • Number of events 6 • 24 months
General disorders Pyrexia	9.6% 5/52 • Number of events 5 • 24 months	12.0% 3/25 • Number of events 4 • 24 months
General disorders Oedema peripheral	7.7% 4/52 • Number of events 9 • 24 months	12.0% 3/25 • Number of events 3 • 24 months
General disorders Infusion site extravasation	5.8% 3/52 • Number of events 4 • 24 months	0.00% 0/25 • 24 months
General disorders Pain	3.8% 2/52 • Number of events 3 • 24 months	12.0% 3/25 • Number of events 5 • 24 months
General disorders Chest pain	1.9% 1/52 • Number of events 1 • 24 months	12.0% 3/25 • Number of events 3 • 24 months
General disorders Influenza like illness	1.9% 1/52 • Number of events 1 • 24 months	12.0% 3/25 • Number of events 4 • 24 months
General disorders Malaise	1.9% 1/52 • Number of events 1 • 24 months	8.0% 2/25 • Number of events 3 • 24 months
General disorders Chest discomfort	0.00% 0/52 • 24 months	8.0% 2/25 • Number of events 3 • 24 months
Immune system disorders Seasonal allergy	7.7% 4/52 • Number of events 5 • 24 months	4.0% 1/25 • Number of events 2 • 24 months
Immune system disorders Hypersensitivity	3.8% 2/52 • Number of events 2 • 24 months	8.0% 2/25 • Number of events 2 • 24 months
Respiratory, thoracic and mediastinal disorders Cough	11.5% 6/52 • Number of events 7 • 24 months	20.0% 5/25 • Number of events 7 • 24 months
Respiratory, thoracic and mediastinal disorders Upper respiratory tract congestion	7.7% 4/52 • Number of events 6 • 24 months	0.00% 0/25 • 24 months
Respiratory, thoracic and mediastinal disorders Nasal congestion	5.8% 3/52 • Number of events 3 • 24 months	4.0% 1/25 • Number of events 1 • 24 months
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	5.8% 3/52 • Number of events 4 • 24 months	12.0% 3/25 • Number of events 3 • 24 months
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	1.9% 1/52 • Number of events 1 • 24 months	12.0% 3/25 • Number of events 3 • 24 months
Product Issues Device occlusion	0.00% 0/52 • 24 months	8.0% 2/25 • Number of events 2 • 24 months
Investigations Urine protein/creatinine ratio increased	5.8% 3/52 • Number of events 5 • 24 months	0.00% 0/25 • 24 months
Investigations Blood creatine increased	3.8% 2/52 • Number of events 5 • 24 months	16.0% 4/25 • Number of events 5 • 24 months
Injury, poisoning and procedural complications Contusion	1.9% 1/52 • Number of events 1 • 24 months	8.0% 2/25 • Number of events 3 • 24 months
Injury, poisoning and procedural complications Fall	1.9% 1/52 • Number of events 1 • 24 months	12.0% 3/25 • Number of events 4 • 24 months
Injury, poisoning and procedural complications Thermal burn	1.9% 1/52 • Number of events 1 • 24 months	8.0% 2/25 • Number of events 4 • 24 months
Injury, poisoning and procedural complications Wound	0.00% 0/52 • 24 months	8.0% 2/25 • Number of events 2 • 24 months
Cardiac disorders Atrial fibrillation	7.7% 4/52 • Number of events 5 • 24 months	4.0% 1/25 • Number of events 3 • 24 months
Cardiac disorders Palpitations	5.8% 3/52 • Number of events 4 • 24 months	8.0% 2/25 • Number of events 2 • 24 months
Cardiac disorders Cardiomyopathy	0.00% 0/52 • 24 months	8.0% 2/25 • Number of events 2 • 24 months
Nervous system disorders Headache	21.2% 11/52 • Number of events 19 • 24 months	20.0% 5/25 • Number of events 9 • 24 months
Nervous system disorders Dizziness	11.5% 6/52 • Number of events 8 • 24 months	8.0% 2/25 • Number of events 2 • 24 months
Nervous system disorders Neuralgia	7.7% 4/52 • Number of events 5 • 24 months	0.00% 0/25 • 24 months
Nervous system disorders Neuropathy peripheral	5.8% 3/52 • Number of events 3 • 24 months	0.00% 0/25 • 24 months
Nervous system disorders Sciatica	5.8% 3/52 • Number of events 5 • 24 months	0.00% 0/25 • 24 months
Nervous system disorders Paraesthesia	3.8% 2/52 • Number of events 2 • 24 months	16.0% 4/25 • Number of events 8 • 24 months
Nervous system disorders Cerebral infarction	0.00% 0/52 • 24 months	8.0% 2/25 • Number of events 2 • 24 months
Nervous system disorders Migraine	0.00% 0/52 • 24 months	8.0% 2/25 • Number of events 3 • 24 months
Blood and lymphatic system disorders Anaemia	7.7% 4/52 • Number of events 4 • 24 months	8.0% 2/25 • Number of events 2 • 24 months
Ear and labyrinth disorders Vertigo	5.8% 3/52 • Number of events 4 • 24 months	4.0% 1/25 • Number of events 1 • 24 months
Gastrointestinal disorders Diarrhoea	19.2% 10/52 • Number of events 15 • 24 months	24.0% 6/25 • Number of events 10 • 24 months
Gastrointestinal disorders Nausea	17.3% 9/52 • Number of events 10 • 24 months	12.0% 3/25 • Number of events 3 • 24 months
Gastrointestinal disorders Abdominal pain	11.5% 6/52 • Number of events 6 • 24 months	0.00% 0/25 • 24 months
Gastrointestinal disorders Vomiting	11.5% 6/52 • Number of events 8 • 24 months	12.0% 3/25 • Number of events 8 • 24 months
Gastrointestinal disorders Gastrooesophageal reflux disease	5.8% 3/52 • Number of events 3 • 24 months	4.0% 1/25 • Number of events 1 • 24 months
Gastrointestinal disorders Abdominal pain upper	3.8% 2/52 • Number of events 2 • 24 months	16.0% 4/25 • Number of events 7 • 24 months
Gastrointestinal disorders Abdominal discomfort	1.9% 1/52 • Number of events 1 • 24 months	12.0% 3/25 • Number of events 3 • 24 months
Skin and subcutaneous tissue disorders Rash	9.6% 5/52 • Number of events 5 • 24 months	8.0% 2/25 • Number of events 3 • 24 months
Skin and subcutaneous tissue disorders dermatitis contact	1.9% 1/52 • Number of events 1 • 24 months	8.0% 2/25 • Number of events 3 • 24 months
Skin and subcutaneous tissue disorders Erythema	1.9% 1/52 • Number of events 1 • 24 months	8.0% 2/25 • Number of events 6 • 24 months
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/52 • 24 months	12.0% 3/25 • Number of events 23 • 24 months
Skin and subcutaneous tissue disorders Urticaria	0.00% 0/52 • 24 months	8.0% 2/25 • Number of events 2 • 24 months
Renal and urinary disorders Proteinuria	11.5% 6/52 • Number of events 7 • 24 months	0.00% 0/25 • 24 months
Renal and urinary disorders Haematuria	5.8% 3/52 • Number of events 4 • 24 months	0.00% 0/25 • 24 months
Musculoskeletal and connective tissue disorders Back pain	15.4% 8/52 • Number of events 12 • 24 months	20.0% 5/25 • Number of events 6 • 24 months
Musculoskeletal and connective tissue disorders Pain in extremity	15.4% 8/52 • Number of events 15 • 24 months	16.0% 4/25 • Number of events 5 • 24 months
Musculoskeletal and connective tissue disorders Muscle spasms	9.6% 5/52 • Number of events 6 • 24 months	12.0% 3/25 • Number of events 3 • 24 months
Musculoskeletal and connective tissue disorders Arthralgia	7.7% 4/52 • Number of events 4 • 24 months	8.0% 2/25 • Number of events 4 • 24 months
Musculoskeletal and connective tissue disorders Musculoskeletal pain	5.8% 3/52 • Number of events 3 • 24 months	8.0% 2/25 • Number of events 2 • 24 months
Musculoskeletal and connective tissue disorders Arthritis	1.9% 1/52 • Number of events 1 • 24 months	8.0% 2/25 • Number of events 2 • 24 months
Musculoskeletal and connective tissue disorders Joint swelling	0.00% 0/52 • 24 months	8.0% 2/25 • Number of events 3 • 24 months
Infections and infestations Nasopharyngitis	21.2% 11/52 • Number of events 21 • 24 months	16.0% 4/25 • Number of events 6 • 24 months
Infections and infestations Sinusitis	15.4% 8/52 • Number of events 9 • 24 months	12.0% 3/25 • Number of events 5 • 24 months
Infections and infestations Upper respiratory tract infection	11.5% 6/52 • Number of events 12 • 24 months	16.0% 4/25 • Number of events 7 • 24 months
Infections and infestations Urinary tract infection	11.5% 6/52 • Number of events 6 • 24 months	12.0% 3/25 • Number of events 4 • 24 months
Infections and infestations Bronchitis	9.6% 5/52 • Number of events 6 • 24 months	20.0% 5/25 • Number of events 7 • 24 months
Infections and infestations Respiratory tract infection	5.8% 3/52 • Number of events 4 • 24 months	4.0% 1/25 • Number of events 3 • 24 months
Infections and infestations Viral infection	5.8% 3/52 • Number of events 3 • 24 months	12.0% 3/25 • Number of events 5 • 24 months
Infections and infestations Pneumonia	3.8% 2/52 • Number of events 2 • 24 months	8.0% 2/25 • Number of events 2 • 24 months
Infections and infestations Viral upper respiratory tract infection	3.8% 2/52 • Number of events 3 • 24 months	8.0% 2/25 • Number of events 2 • 24 months
Infections and infestations Gastrointestinal viral infection	1.9% 1/52 • Number of events 1 • 24 months	8.0% 2/25 • Number of events 4 • 24 months
Infections and infestations Pharyngitis	1.9% 1/52 • Number of events 1 • 24 months	16.0% 4/25 • Number of events 4 • 24 months
Infections and infestations Gastroenteritis	0.00% 0/52 • 24 months	12.0% 3/25 • Number of events 3 • 24 months

Additional Information

Sari Alon, MSc

Protalix Ltd.

Phone: +972-4-9028100

Email: sari@protalix.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place