Fabry Disease
Conditions
Keywords
PRX-102, pegunigalsidase alfa, Fabry Disease
Brief summary
To evaluate the ongoing safety, tolerability, and efficacy parameters of PRX-102 in adult Fabry patients who have successfully completed treatment with PRX-102 in studies PB-102-F01 and PB-102-F02.
Detailed description
An open-label study to evaluate the ongoing safety, tolerability and efficacy parameters of PRX-102 in adult Fabry patients (≥18 years of age). Patients enrolled received 1.0 mg/kg of PRX-102 as an intravenous infusion every 2 weeks (+/- 3 days) for up to 60 months and no less than 36 months.
Interventions
BIOLOGICALPRX-102 (pegunigalsidase alfa)
PRX-102 1 mg/kg every 2 weeks
Sponsors
Chiesi Farmaceutici S.p.A.
Protalix
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Completion of study PB-102-F02 * The patient signs informed consent * Female patients and male patients whose co-partners were of child-bearing potential agree to use a medically acceptable method of contraception, not including the rhythm method. Acceptable methods of contraception include hormonal products, intrauterine device, or male or female condoms. Contraception should be used throughout the duration of the study and for 3 months after termination of treatment.
Exclusion criteria
* Presence of any medical, emotional, behavioral or psychological condition that, in the judgment of the Investigator and/or Medical Director, would interfere with the patient's compliance with the requirements of the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.03 | Every two weeks up to 60 months | Results represent the number of treatment-emergent adverse events (TEAE) that were considered definitely, probably or possibly related to study treatment. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Plasma Lyso-Gb3 Concentration | Baseline and month 60 | Globotriaosylsphingosine (Lyso-Gb3) is Fabry disease specific biomarker, which was measured at Baseline, every 3 months up to 24 months and then every 6 months up to the end of the study. Baseline and Month 60 and change from Baseline reported. |
| Estimated Glomerular Filtration Rate (eGFR) | Baseline and Month 60 | eGFR was calculated based on the serum creatinine values according to the CKD-EPI equation. The absolute change in eGFR from baseline measurement at visit 1 to Month 60 was summarized using descriptive statistics. Baseline and month 60 reported. |
Countries
Paraguay, Spain, United Kingdom, United States
Participant flow
Recruitment details
Adult Fabry disease patients who have successfully completed treatment with PRX-102 in previous studies PB-102-F01 and PB-102-F02
Pre-assignment details
A total of 15 adult patients (8 male and 7 female) who completed study PB-102-F02 were enrolled in this study and included in both the Safety and Efficacy populations.
Participants by arm
| Arm | Count |
|---|---|
| PRX-102 (Pegunigalsidase Alfa) PRX-102 (pegunigalsidase alfa) 1.0 mg/kg IV every 2 weeks (+/- 3 days) | 15 |
| Total | 15 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Pregnancy | 1 |
| Overall Study | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | PRX-102 (Pegunigalsidase Alfa) |
|---|---|
| Age, Categorical <=18 years | 1 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 14 Participants |
| Age, Continuous | 33.4 years STANDARD_DEVIATION 12.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 12 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 11 Participants |
| Region of Enrollment Paraguay | 1 participants |
| Region of Enrollment Spain | 2 participants |
| Region of Enrollment United Kingdom | 1 participants |
| Region of Enrollment United States | 11 participants |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 15 |
| other Total, other adverse events | 15 / 15 |
| serious Total, serious adverse events | 3 / 15 |
Outcome results
Primary
Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.03
Results represent the number of treatment-emergent adverse events (TEAE) that were considered definitely, probably or possibly related to study treatment.
Time frame: Every two weeks up to 60 months
Population: Safety population is defined as all patients who received any dose (partial or complete) of study treatment as part of study PB-102-F03. Efficacy population is defined as all patients who received at least one complete dose of the study treatment as part of study PB-102-F03
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PRX-102 (Pegunigalsidase Alfa) | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.03 | Safety Analysis Set : At least 1 TEAE leading to death | 1 participants |
| PRX-102 (Pegunigalsidase Alfa) | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.03 | Safety Analysis Set : At lease 1 TEAE | 13 participants |
| PRX-102 (Pegunigalsidase Alfa) | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.03 | Safety Analysis Set : At least 1 mild or moderate TEAE | 13 participants |
| PRX-102 (Pegunigalsidase Alfa) | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.03 | Safety Analysis Set : At least 1 severe TEAE | 5 participants |
| PRX-102 (Pegunigalsidase Alfa) | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.03 | Safety Analysis Set : At least 1 SAE | 2 participants |
| PRX-102 (Pegunigalsidase Alfa) | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.03 | Safety Analysis Set : At least 1 definitely, probably or possibly related | 4 participants |
| PRX-102 (Pegunigalsidase Alfa) | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.03 | Safety Analysis Set : At least 1 TEAE leading to discontinuation | 1 participants |
Other Pre-specified
Estimated Glomerular Filtration Rate (eGFR)
eGFR was calculated based on the serum creatinine values according to the CKD-EPI equation. The absolute change in eGFR from baseline measurement at visit 1 to Month 60 was summarized using descriptive statistics. Baseline and month 60 reported.
Time frame: Baseline and Month 60
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PRX-102 (Pegunigalsidase Alfa) | Estimated Glomerular Filtration Rate (eGFR) | Month 60 | 97.0 ml/min/1.73 m^2 | Standard Error 6.4 |
| PRX-102 (Pegunigalsidase Alfa) | Estimated Glomerular Filtration Rate (eGFR) | Baseline | 111.7 ml/min/1.73 m^2 | Standard Error 5.5 |
| PRX-102 (Pegunigalsidase Alfa) | Estimated Glomerular Filtration Rate (eGFR) | Change from Baseline to Month 60 | -10.9 ml/min/1.73 m^2 | Standard Error 2 |
| Male | Estimated Glomerular Filtration Rate (eGFR) | Month 60 | 100.0 ml/min/1.73 m^2 | Standard Error 8.3 |
| Male | Estimated Glomerular Filtration Rate (eGFR) | Baseline | 118.1 ml/min/1.73 m^2 | Standard Error 7.7 |
| Male | Estimated Glomerular Filtration Rate (eGFR) | Change from Baseline to Month 60 | -14.5 ml/min/1.73 m^2 | Standard Error 1.7 |
| Female | Estimated Glomerular Filtration Rate (eGFR) | Baseline | 104.45 ml/min/1.73 m^2 | Standard Error 7.5 |
| Female | Estimated Glomerular Filtration Rate (eGFR) | Change from Baseline to Month 60 | -5.6 ml/min/1.73 m^2 | Standard Error 2.6 |
| Female | Estimated Glomerular Filtration Rate (eGFR) | Month 60 | 92.4 ml/min/1.73 m^2 | Standard Error 11.4 |
Other Pre-specified
Plasma Lyso-Gb3 Concentration
Globotriaosylsphingosine (Lyso-Gb3) is Fabry disease specific biomarker, which was measured at Baseline, every 3 months up to 24 months and then every 6 months up to the end of the study. Baseline and Month 60 and change from Baseline reported.
Time frame: Baseline and month 60
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PRX-102 (Pegunigalsidase Alfa) | Plasma Lyso-Gb3 Concentration | Month 60 | 6.4 ng/mL | Standard Error 1.5 |
| PRX-102 (Pegunigalsidase Alfa) | Plasma Lyso-Gb3 Concentration | Baseline | 70.8 ng/mL | Standard Error 20.4 |
| PRX-102 (Pegunigalsidase Alfa) | Plasma Lyso-Gb3 Concentration | Change from Baseline to Month 60 | -68.4 ng/mL | Standard Error 25 |
| Male | Plasma Lyso-Gb3 Concentration | Month 60 | 9.2 ng/mL | Standard Error 1.6 |
| Male | Plasma Lyso-Gb3 Concentration | Baseline | 124.4 ng/mL | Standard Error 25.9 |
| Male | Plasma Lyso-Gb3 Concentration | Change from Baseline to Month 60 | -111.0 ng/mL | Standard Error 31 |
| Female | Plasma Lyso-Gb3 Concentration | Baseline | 9.6 ng/mL | Standard Error 2.1 |
| Female | Plasma Lyso-Gb3 Concentration | Change from Baseline to Month 60 | -4.6 ng/mL | Standard Error 0.9 |
| Female | Plasma Lyso-Gb3 Concentration | Month 60 | 2.1 ng/mL | Standard Error 0.9 |