Trial Outcomes & Findings for Safety, Efficacy, & PK of PRX-102 in Patients With Fabry Disease Administered Intravenously Every 4 Weeks (NCT NCT03180840)

NCT ID: NCT03180840

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: 30 participants
• Primary outcome timeframe: Month 12
• Results posted on: 2023-09-13

Participant Flow

Patients who were treated with agalsidase beta or agalsidase alfa for at least three years and have been on a stable dose (>80% labelled dose/kg) for at least 6 months.

Screening details: A total of 52 patients were screened of whom 30 patients (24 males and 6 females) were enrolled and switched from agalsidase alfa or agalsidase beta to pegunigalsidase alfa over a 52-week period, of whom 29 patients (23 males and 6 females) completed the study.

Participant milestones

Measure	Pegunigalsidase Alfa Pegunigalsidase alfa 2.0 mg/kg intravenous infusion every 4 weeks for 12 months
Overall Study STARTED	30
Overall Study COMPLETED	29
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Measure	Pegunigalsidase Alfa Pegunigalsidase alfa 2.0 mg/kg intravenous infusion every 4 weeks for 12 months
Overall Study Withdrawal by Subject	1

Baseline Characteristics

Safety, Efficacy, & PK of PRX-102 in Patients With Fabry Disease Administered Intravenously Every 4 Weeks

Baseline characteristics by cohort

Measure	Pegunigalsidase Alfa n=30 Participants Pegunigalsidase alfa 2 mg/kg intravenous infusion every 4 weeks Pegunigalsidase alfa: Pegunigalsidase alfa 2 mg/kg every 4 weeks
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	30 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Age, Continuous	40.5 years STANDARD_DEVIATION 11.3 • n=5 Participants
Sex: Female, Male Female	6 Participants n=5 Participants
Sex: Female, Male Male	24 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	30 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment Belgium	2 participants n=5 Participants
Region of Enrollment United States	18 participants n=5 Participants
Region of Enrollment Norway	1 participants n=5 Participants
Region of Enrollment Denmark	1 participants n=5 Participants
Region of Enrollment United Kingdom	2 participants n=5 Participants
Region of Enrollment Italy	3 participants n=5 Participants
Region of Enrollment Czechia	3 participants n=5 Participants
Previous Enzyme Replacement Therapy (ERT) Agalsidase alfa	7 Participants n=5 Participants
Previous Enzyme Replacement Therapy (ERT) Agalsidase beta	23 Participants n=5 Participants

PRIMARY outcome

Timeframe: Month 12

Results 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=30 Participants Pegunigalsidase alfa 2.0 mg/kg intravenous infusion every 4 weeks for 12 months	Males Number of Male Subjects Analysed	Females Number of Females Analysed
Number of Participants With Treatment-related Adverse Events (TEAE) as Assessed by CTCAE v4.03 At least 1 TEAE	27 participants	—	—
Number of Participants With Treatment-related Adverse Events (TEAE) as Assessed by CTCAE v4.03 At least 1 mild or moderate TEAE	26 participants	—	—
Number of Participants With Treatment-related Adverse Events (TEAE) as Assessed by CTCAE v4.03 At least 1 severe TEAE	2 participants	—	—
Number of Participants With Treatment-related Adverse Events (TEAE) as Assessed by CTCAE v4.03 At least 1 serious TEAE	2 participants	—	—
Number of Participants With Treatment-related Adverse Events (TEAE) as Assessed by CTCAE v4.03 At least 1 non-serious TEAE	26 participants	—	—
Number of Participants With Treatment-related Adverse Events (TEAE) as Assessed by CTCAE v4.03 At least 1 related TEAE	9 participants	—	—
Number of Participants With Treatment-related Adverse Events (TEAE) as Assessed by CTCAE v4.03 At least 1 related mild or moderate	9 participants	—	—
Number of Participants With Treatment-related Adverse Events (TEAE) as Assessed by CTCAE v4.03 At least 1 related severe TEAE	0 participants	—	—
Number of Participants With Treatment-related Adverse Events (TEAE) as Assessed by CTCAE v4.03 At least 1 related serious TEAE	0 participants	—	—
Number of Participants With Treatment-related Adverse Events (TEAE) as Assessed by CTCAE v4.03 At least 1 TEAE leading to withdrawal	0 participants	—	—
Number of Participants With Treatment-related Adverse Events (TEAE) 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)

Population: Any subjects who have at least one post-baseline observation.

eGFR was calculated based on the serum creatinine values that were assessed at Day 1, weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 according to the CKD-EPI formula, baseline and Month 12 (week 52) reported. The change in eGFR from baseline measurement at Day 1 prior to first PRX-102 infusion to last measurement at Month 12 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 n=29 Participants Pegunigalsidase alfa 2.0 mg/kg intravenous infusion every 4 weeks for 12 months	Males n=23 Participants Number of Male Subjects Analysed	Females n=6 Participants Number of Females Analysed
Estimated Glomerular Filtration Rate (eGFR) Baseline	99.44 mL/min/1.73m^2 Standard Error 4.15	100.68 mL/min/1.73m^2 Standard Error 4.96	94.69 mL/min/1.73m^2 Standard Error 6.76
Estimated Glomerular Filtration Rate (eGFR) Month 12 (week 52)	100.65 mL/min/1.73m^2 Standard Error 3.14	103.24 mL/min/1.73m^2 Standard Error 3.46	91.15 mL/min/1.73m^2 Standard Error 6.39
Estimated Glomerular Filtration Rate (eGFR) Change from Baseline to Month 12 (week 52)	-1.27 mL/min/1.73m^2 Standard Error 1.39	-0.64 mL/min/1.73m^2 Standard Error 1.57	-3.54 mL/min/1.73m^2 Standard Error 3.12

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline and month 12 (Week 52)

Population: Any subjects who have at least one post-baseline observation.

Globotriaosylsphingosine (Lyso-Gb3) is Fabry disease specific biomarker that can assess treatment outcome, for which was measured at Baseline, weeks 12, 24, 40 and 52. The mean Plasma Lyso-Gb3 concentrations at baseline and Month 12 (week 52) and the mean change from Baseline reported.

The change from baseline to month 12 was calculated for each subject and the reported values is the mean (Standard Error) of these changes.

Outcome measures

Measure	PRX-102 n=29 Participants Pegunigalsidase alfa 2.0 mg/kg intravenous infusion every 4 weeks for 12 months	Males n=23 Participants Number of Male Subjects Analysed	Females n=6 Participants Number of Females Analysed
Plasma Lyso-Gb3 Baseline	19.36 nM Standard Error 3.35	23.27 nM Standard Error 3.82	4.35 nM Standard Error 1.00
Plasma Lyso-Gb3 Month 12 (week 52)	22.23 nM Standard Error 3.60	27.05 nM Standard Error 4.00	4.52 nM Standard Error 1.10
Plasma Lyso-Gb3 Change from Baseline to Month 12 (week 52)	3.01 nM Standard Error 0.94	3.79 nM Standard Error 1.14	0.17 nM Standard Error 0.34

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline and 12 months (week 52)

Population: Any subjects who have at least one post-baseline observation.

The 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). The change from baseline to month 12 was calculated for each subject and the reported value is the mean (Standard Error) of these changes.

Outcome measures

Measure	PRX-102 n=29 Participants Pegunigalsidase alfa 2.0 mg/kg intravenous infusion every 4 weeks for 12 months	Males Number of Male Subjects Analysed	Females Number of Females Analysed
Quality of Life by EQ-VAS Baseline	78.3 scores on a scale Standard Error 3.1	—	—
Quality of Life by EQ-VAS Month 12 (week 52)	82.1 scores on a scale Standard Error 2.9	—	—
Quality of Life by EQ-VAS Change from Baseline to Month 12 (week 52)	3.0 scores on a scale Standard Error 2.2	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 1, Month 9 or 11, and Month 12

Population: All subjects who received at least one dose of PRX-102 and for whom a sufficient number of evaluable samples were available to determine at least 1 PK parameter.

Pharmacokinetic (PK) parameters were derived from the plasma concentration versus time profiles. Cmax is the maximal plasma concentration of a drug after administration. Results reported represent the values following a single dosing of the study drug.

Outcome measures

Measure	PRX-102 n=30 Participants Pegunigalsidase alfa 2.0 mg/kg intravenous infusion every 4 weeks for 12 months	Males Number of Male Subjects Analysed	Females Number of Females Analysed
Pharmacokinetics - Cmax	35876.7 ng/mL Standard Deviation 11942.2	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 1, Month 9 or 11, and Month 12.

Population: All subjects who received at least one dose or PRX-102 and for whom a sufficient number of evaluable samples were available to determine at least 1 PK parameter.

PK parameters were derived from the plasma concentration versus time profiles. AUC is the area under the plasma concentration curve from 0 hour to infinity. Results reported represent the values following a single dosing of the study drug.

Outcome measures

Measure	PRX-102 n=30 Participants Pegunigalsidase alfa 2.0 mg/kg intravenous infusion every 4 weeks for 12 months	Males Number of Male Subjects Analysed	Females Number of Females Analysed
Pharmacokinetics - AUC	1797464.1 ng*hr/mL Standard Deviation 822632.4	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 1, Month 9 or 11, and Month 12.

Population: All subjects who received at least one dose of PRX-102 and for whom a sufficient number of evaluable samples were available to determine at least 1 PK parameter

PK parameters were derived from the plasma concentration versus time profiles. t1/2 = half life. Results reported represent the values following a single dosing of the study drug.

Outcome measures

Measure	PRX-102 n=30 Participants Pegunigalsidase alfa 2.0 mg/kg intravenous infusion every 4 weeks for 12 months	Males Number of Male Subjects Analysed	Females Number of Females Analysed
Pharmacokinetics - Terminal Half Life	100.1 hour Standard Deviation 58.3	—	—

Adverse Events

All Patients

Serious events: 2 serious events

Other events: 27 other events

Deaths: 0 deaths

Serious adverse events

Measure	All Patients n=30 participants at risk Analysis of AEs was performed on TEAEs, defined as AEs occurring after the start of the first infusion with pegunigalsidase alfa.
Injury, poisoning and procedural complications Overdose	3.3% 1/30 • Number of events 1 • Adverse events were collected from the start of treatment until 30 days following the final study dose, an average of 13 months.
Injury, poisoning and procedural complications Road Traffic Accident	3.3% 1/30 • Number of events 1 • Adverse events were collected from the start of treatment until 30 days following the final study dose, an average of 13 months.

Other adverse events

Measure	All Patients n=30 participants at risk Analysis of AEs was performed on TEAEs, defined as AEs occurring after the start of the first infusion with pegunigalsidase alfa.
Injury, poisoning and procedural complications Infusion related reaction	16.7% 5/30 • Number of events 17 • Adverse events were collected from the start of treatment until 30 days following the final study dose, an average of 13 months.
Injury, poisoning and procedural complications Contusion	6.7% 2/30 • Number of events 2 • Adverse events were collected from the start of treatment until 30 days following the final study dose, an average of 13 months.
Respiratory, thoracic and mediastinal disorders Cough	13.3% 4/30 • Number of events 4 • Adverse events were collected from the start of treatment until 30 days following the final study dose, an average of 13 months.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	10.0% 3/30 • Number of events 4 • Adverse events were collected from the start of treatment until 30 days following the final study dose, an average of 13 months.
Nervous system disorders Headache	10.0% 3/30 • Number of events 4 • Adverse events were collected from the start of treatment until 30 days following the final study dose, an average of 13 months.
Nervous system disorders Paraesthesia	10.0% 3/30 • Number of events 3 • Adverse events were collected from the start of treatment until 30 days following the final study dose, an average of 13 months.
Nervous system disorders Neuralgia	6.7% 2/30 • Number of events 2 • Adverse events were collected from the start of treatment until 30 days following the final study dose, an average of 13 months.
General disorders Pain	10.0% 3/30 • Number of events 9 • Adverse events were collected from the start of treatment until 30 days following the final study dose, an average of 13 months.
General disorders Fatigue	16.7% 5/30 • Number of events 6 • Adverse events were collected from the start of treatment until 30 days following the final study dose, an average of 13 months.
General disorders Chest discomfort	6.7% 2/30 • Number of events 2 • Adverse events were collected from the start of treatment until 30 days following the final study dose, an average of 13 months.
General disorders Pyrexia	6.7% 2/30 • Number of events 2 • Adverse events were collected from the start of treatment until 30 days following the final study dose, an average of 13 months.
Ear and labyrinth disorders Ear Pain	6.7% 2/30 • Number of events 2 • Adverse events were collected from the start of treatment until 30 days following the final study dose, an average of 13 months.
Ear and labyrinth disorders Hypoacusis	6.7% 2/30 • Number of events 2 • Adverse events were collected from the start of treatment until 30 days following the final study dose, an average of 13 months.
Psychiatric disorders Anxiety	6.7% 2/30 • Number of events 2 • Adverse events were collected from the start of treatment until 30 days following the final study dose, an average of 13 months.
Gastrointestinal disorders Diarrhoea	10.0% 3/30 • Number of events 4 • Adverse events were collected from the start of treatment until 30 days following the final study dose, an average of 13 months.
Gastrointestinal disorders Nausea	13.3% 4/30 • Number of events 4 • Adverse events were collected from the start of treatment until 30 days following the final study dose, an average of 13 months.
Gastrointestinal disorders Gastroesophageal Reflux Disease	6.7% 2/30 • Number of events 2 • Adverse events were collected from the start of treatment until 30 days following the final study dose, an average of 13 months.
Gastrointestinal disorders Vomiting	6.7% 2/30 • Number of events 2 • Adverse events were collected from the start of treatment until 30 days following the final study dose, an average of 13 months.
Musculoskeletal and connective tissue disorders Pain in extremity	10.0% 3/30 • Number of events 4 • Adverse events were collected from the start of treatment until 30 days following the final study dose, an average of 13 months.
Musculoskeletal and connective tissue disorders Myalgia	6.7% 2/30 • Number of events 2 • Adverse events were collected from the start of treatment until 30 days following the final study dose, an average of 13 months.
Infections and infestations Nasopharyngitis	20.0% 6/30 • Number of events 7 • Adverse events were collected from the start of treatment until 30 days following the final study dose, an average of 13 months.
Infections and infestations Gastroenteritis	6.7% 2/30 • Number of events 4 • Adverse events were collected from the start of treatment until 30 days following the final study dose, an average of 13 months.
Infections and infestations Sinusitis	10.0% 3/30 • Number of events 3 • Adverse events were collected from the start of treatment until 30 days following the final study dose, an average of 13 months.
Infections and infestations Upper respiratory tract infection	6.7% 2/30 • Number of events 3 • Adverse events were collected from the start of treatment until 30 days following the final study dose, an average of 13 months.
Infections and infestations Viral infections	10.0% 3/30 • Number of events 3 • Adverse events were collected from the start of treatment until 30 days following the final study dose, an average of 13 months.
Infections and infestations Gastroenteritis viral	6.7% 2/30 • Number of events 2 • Adverse events were collected from the start of treatment until 30 days following the final study dose, an average of 13 months.
Infections and infestations Influenza	6.7% 2/30 • Number of events 2 • Adverse events were collected from the start of treatment until 30 days following the final study dose, an average of 13 months.
Infections and infestations Pharyngitis streptococcal	6.7% 2/30 • Number of events 2 • Adverse events were collected from the start of treatment until 30 days following the final study dose, an average of 13 months.

Additional Information

Sari Alon

Protalix Ltd.

Phone: +972-4-9028100

Email: sari@protalix.com

Results disclosure agreements

• Principal investigator is a sponsor employee The clinical trial agreement 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