Focal Segmental Glomerulosclerosis
Conditions
Keywords
calcineurin inhibitors, Focal Segmental Glomerulosclerosis
Brief summary
Evaluating the Efficacy and Safety of Voclosporin in Achieving Complete or Partial Remission of Proteinuria in Subjects with Focal Segmental Glomerulosclerosis
Detailed description
The aim of the current study to assess the efficacy of voclosporin in achieving complete or partial remission of proteinuria after 24 weeks of therapy in subjects with focal segmental glomerulosclerosis (FSGS). As well as to assess the safety and tolerability of voclosporin over 24 weeks in subjects with FSGS.
Interventions
DRUGVoclosporin
Voclosporin softgel capsules. Up to 10 subjects will be enrolled into Cohort 1 and take up to 3 capsules twice daily (BID). The dose of voclosporin for Cohort 2 (at least 10 subjects) will be determined by analysis of efficacy and safety data at Week 12 from the first 5 or 6 subjects in Cohort 1.
Sponsors
Aurinia Pharmaceuticals Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Primary FSGS diagnosed by renal biopsy. 2. Urine protein creatinine ratio (UPCR) ≥2.0 mg/mg, serum albumin ≤3.2 g/dL and can be immunosuppressant treatment-naïve, or receiving treatment with steroids. 3. Stable proteinuria, renal function, and BP.
Exclusion criteria
1. Clinical or histologic evidence of secondary FSGS. 2. Histologic evidence of collapsing variant FSGS. 3. eGFR as calculated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation of ≤30 mL/minute/1.73 m2 at initial screening assessment or ≤45 mL/minute/1.73 m2 at last qualifying assessment. 4. Currently requiring renal dialysis (hemodialysis or peritoneal dialysis) or expected to require dialysis during the study period. 5. Current or medical history of: * Congenital or acquired immunodeficiency. * In the opinion of the Investigator, clinically significant drug or alcohol abuse within 2 years prior to screening. * Malignancy within 5 years of screening, with the exception of basal and squamous cell carcinomas treated by complete excision. * Current or past lymphoproliferative disease or previous total lymphoid irradiation. * Severe viral infection within 3 months of screening, or known HIV infection. Severe viral infection is defined as active disease requiring antiviral therapy. * Active tuberculosis (TB) or known history of TB/evidence of old TB if not taking prophylaxis with isoniazid.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Subjects With Remission of Proteinuria | 24 weeks | Complete remission OR Partial remission |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Subjects With Complete Remission or Partial Remission of Proteinuria | Weeks 8 and 12 | Complete remission or partial remission of proteinuria |
| Proportion of Subjects With Complete Remission of Proteinuria | Weeks 8, 12, and 24 | Complete remission of proteinuria |
| Proportion of Subjects With Reduction of Proteinuria | Weeks 8, 12, and 24 | Reduction of proteinuria |
| Time to First Occurrence of Complete or Partial Remission of Proteinuria | Up to 26 weeks | Complete OR partial remission of proteinuria |
| Time to First Occurrence of Complete Remission of Proteinuria | Up to 26 weeks | Complete remission of proteinuria |
| Time to First Occurrence of Partial Remission of Proteinuria | Up to 26 weeks | Partial remission of proteinuria |
| Time to First Occurrence of 50% Reduction in Urine Protein Creatinine Ratio (UPCR) From Baseline | Up to 26 weeks | 50% reduction in Urine Protein Creatinine Ratio (UPCR) from baseline |
| Duration of Reduced Urine Protein Creatinine Ratio (UPCR) | Up to 26 weeks | Duration of reduced Urine Protein Creatinine Ratio (UPCR) |
| Proportion of Subjects With Partial Remission of Proteinuria | Weeks 8, 12, and 24 | Partial remission of proteinuria |
| Proportion of Subjects With a Confirmed Decrease From Baseline in Estimated Glomerular Filtration Rate (eGFR) | Weeks 2,4,8,12,18,24 | Utilizing the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) formula |
| Proportion of Subjects With a Confirmed Increase in Estimated Glomerular Filtration Rate (eGFR) | Week 24 to Week 26 | Increase in Estimated Glomerular Filtration Rate (eGFR) |
| Change in Urine Protein Creatinine Ratio (UPCR) | Week 24 and Week 26 | Change in Urine Protein Creatinine Ratio (UPCR) |
| Change in Estimated Glomerular Filtration Rate (eGFR) | Week 24 and Week 26 | Change in estimated Glomerular Filtration Rate (eGFR) |
| Change From Baseline in Serum Creatinine, Serum Albumin and Estimate Glomerular Filtration Rate (eGFR) | Weeks 2,4,8,12,18,24 | Change from baseline in serum creatinine, serum albumin and estimate Glomerular Filtration Rate (eGFR) |
| Quality of Life Assessments | Week 24 | Mean change in Patient Reported Outcome Measurement Information System (PROMIS) measures |
| Safety and Tolerability (Treatment-Emergent Adverse Events) | 24 weeks | Incidence and number of treatment-emergent adverse events |
| Renal Biopsy | 24 weeks | Descriptive analyses of changes in histopathology will be evaluated in post treatment renal biopsies in a subset of patients |
| Change From Baseline in Urine Protein Creatinine Ratio (UPCR) | Weeks 2,4,8,12,18,24 | Change from baseline in Urine Protein Creatinine Ratio (UPCR) |
Countries
Dominican Republic, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Voclosporin Cohort 1 Cohort 1:
Maximum dose of 3 capsules voclosporin (23.7 mg total) twice daily | 5 |
| Voclosporin Cohort 2 Trial ended prematurely before any patients were enrolled into Cohort 2
Cohort 2:
When Cohort 1 have completed 12 weeks of treatment with voclosporin, the top line efficacy and safety data will be analyzed to determine the dose level for Cohort 2. The selected dose may be higher or lower than 23.7 mg twice daily.
The maximum dose possible for Cohort 2 will be 39.5 mg (5 capsules) twice daily. | 0 |
| Total | 5 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Voclosporin Cohort 1 | Total |
|---|---|---|
| Age, Continuous | 36.2 years STANDARD_DEVIATION 20.71 | 36.2 years STANDARD_DEVIATION 20.71 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 3 Participants | 3 Participants |
| Region of Enrollment Dominican Republic | 2 participants | 2 participants |
| Region of Enrollment United States | 3 participants | 3 participants |
| Sex: Female, Male Female | 2 Participants | 2 Participants |
| Sex: Female, Male Male | 3 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 5 | 0 / 5 | 0 / 5 | 0 / 0 |
| other Total, other adverse events | 2 / 5 | 0 / 5 | 5 / 5 | 0 / 0 |
| serious Total, serious adverse events | 0 / 5 | 0 / 5 | 1 / 5 | 0 / 0 |
Outcome results
Primary
Proportion of Subjects With Remission of Proteinuria
Complete remission OR Partial remission
Time frame: 24 weeks
Population: Due to difficulties enrolling appropriate Focal Segmental Glomerulosclerosis (FSGS) patients, Aurinia terminated the clinical trial early. Focal Segmental Glomerulosclerosis (FSGS) is a rare disease with an estimated 40,000 adult patients in the USA. Only five subjects were enrolled into the clinical trial. The primary and secondary endpoints were not assessed due to insufficient data collected
Secondary
Change From Baseline in Serum Creatinine, Serum Albumin and Estimate Glomerular Filtration Rate (eGFR)
Change from baseline in serum creatinine, serum albumin and estimate Glomerular Filtration Rate (eGFR)
Time frame: Weeks 2,4,8,12,18,24
Population: Due to difficulties enrolling appropriate Focal Segmental Glomerulosclerosis (FSGS) patients, Aurinia terminated the clinical trial early. Focal Segmental Glomerulosclerosis (FSGS) is a rare disease with an estimated 40,000 adult patients in the USA. Only five subjects were enrolled into the clinical trial. The primary and secondary endpoints were not assessed due to insufficient data collected.
Secondary
Change From Baseline in Urine Protein Creatinine Ratio (UPCR)
Change from baseline in Urine Protein Creatinine Ratio (UPCR)
Time frame: Weeks 2,4,8,12,18,24
Population: Due to difficulties enrolling appropriate Focal Segmental Glomerulosclerosis (FSGS) patients, Aurinia terminated the clinical trial early. Focal Segmental Glomerulosclerosis (FSGS) is a rare disease with an estimated 40,000 adult patients in the USA. Only five subjects were enrolled into the clinical trial. The primary and secondary endpoints were not assessed due to insufficient data collected.
Secondary
Change in Estimated Glomerular Filtration Rate (eGFR)
Change in estimated Glomerular Filtration Rate (eGFR)
Time frame: Week 24 and Week 26
Population: Due to difficulties enrolling appropriate Focal Segmental Glomerulosclerosis (FSGS) patients, Aurinia terminated the clinical trial early. Focal Segmental Glomerulosclerosis (FSGS) is a rare disease with an estimated 40,000 adult patients in the USA. Only five subjects were enrolled into the clinical trial. The primary and secondary endpoints were not assessed due to insufficient data collected.
Secondary
Change in Urine Protein Creatinine Ratio (UPCR)
Change in Urine Protein Creatinine Ratio (UPCR)
Time frame: Week 24 and Week 26
Population: Due to difficulties enrolling appropriate Focal Segmental Glomerulosclerosis (FSGS) patients, Aurinia terminated the clinical trial early. Focal Segmental Glomerulosclerosis (FSGS) is a rare disease with an estimated 40,000 adult patients in the USA. Only five subjects were enrolled into the clinical trial. The primary and secondary endpoints were not assessed due to insufficient data collected.
Secondary
Duration of Reduced Urine Protein Creatinine Ratio (UPCR)
Duration of reduced Urine Protein Creatinine Ratio (UPCR)
Time frame: Up to 26 weeks
Population: Due to difficulties enrolling appropriate Focal Segmental Glomerulosclerosis (FSGS) patients, Aurinia terminated the clinical trial early. Focal Segmental Glomerulosclerosis (FSGS) is a rare disease with an estimated 40,000 adult patients in the USA. Only five subjects were enrolled into the clinical trial. The primary and secondary endpoints were not assessed due to insufficient data collected.
Secondary
Proportion of Subjects With a Confirmed Decrease From Baseline in Estimated Glomerular Filtration Rate (eGFR)
Utilizing the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) formula
Time frame: Weeks 2,4,8,12,18,24
Population: Due to difficulties enrolling appropriate Focal Segmental Glomerulosclerosis (FSGS) patients, Aurinia terminated the clinical trial early. Focal Segmental Glomerulosclerosis (FSGS) is a rare disease with an estimated 40,000 adult patients in the USA. Only five subjects were enrolled into the clinical trial. The primary and secondary endpoints were not assessed due to insufficient data collected.
Secondary
Proportion of Subjects With a Confirmed Increase in Estimated Glomerular Filtration Rate (eGFR)
Increase in Estimated Glomerular Filtration Rate (eGFR)
Time frame: Week 24 to Week 26
Population: Due to difficulties enrolling appropriate Focal Segmental Glomerulosclerosis (FSGS) patients, Aurinia terminated the clinical trial early. Focal Segmental Glomerulosclerosis (FSGS) is a rare disease with an estimated 40,000 adult patients in the USA. Only five subjects were enrolled into the clinical trial. The primary and secondary endpoints were not assessed due to insufficient data collected.
Secondary
Proportion of Subjects With Complete Remission of Proteinuria
Complete remission of proteinuria
Time frame: Weeks 8, 12, and 24
Population: Due to difficulties enrolling appropriate Focal Segmental Glomerulosclerosis (FSGS) patients, Aurinia terminated the clinical trial early. Focal Segmental Glomerulosclerosis (FSGS) is a rare disease with an estimated 40,000 adult patients in the USA. Only five subjects were enrolled into the clinical trial. The primary and secondary endpoints were not assessed due to insufficient data collected.
Secondary
Proportion of Subjects With Complete Remission or Partial Remission of Proteinuria
Complete remission or partial remission of proteinuria
Time frame: Weeks 8 and 12
Population: Due to difficulties enrolling appropriate Focal Segmental Glomerulosclerosis (FSGS) patients, Aurinia terminated the clinical trial early. Focal Segmental Glomerulosclerosis (FSGS) is a rare disease with an estimated 40,000 adult patients in the USA. Only five subjects were enrolled into the clinical trial. The primary and secondary endpoints were not assessed due to insufficient data collected.
Secondary
Proportion of Subjects With Partial Remission of Proteinuria
Partial remission of proteinuria
Time frame: Weeks 8, 12, and 24
Population: Due to difficulties enrolling appropriate Focal Segmental Glomerulosclerosis (FSGS) patients, Aurinia terminated the clinical trial early. Focal Segmental Glomerulosclerosis (FSGS) is a rare disease with an estimated 40,000 adult patients in the USA. Only five subjects were enrolled into the clinical trial. The primary and secondary endpoints were not assessed due to insufficient data collected.
Secondary
Proportion of Subjects With Reduction of Proteinuria
Reduction of proteinuria
Time frame: Weeks 8, 12, and 24
Population: Due to difficulties enrolling appropriate Focal Segmental Glomerulosclerosis (FSGS) patients, Aurinia terminated the clinical trial early. Focal Segmental Glomerulosclerosis (FSGS) is a rare disease with an estimated 40,000 adult patients in the USA. Only five subjects were enrolled into the clinical trial. The primary and secondary endpoints were not assessed due to insufficient data collected.
Secondary
Quality of Life Assessments
Mean change in Patient Reported Outcome Measurement Information System (PROMIS) measures
Time frame: Week 24
Population: Due to difficulties enrolling appropriate Focal Segmental Glomerulosclerosis (FSGS) patients, Aurinia terminated the clinical trial early. Focal Segmental Glomerulosclerosis (FSGS) is a rare disease with an estimated 40,000 adult patients in the USA. Only five subjects were enrolled into the clinical trial. The primary and secondary endpoints were not assessed due to insufficient data collected.
Secondary
Quality of Life Assessments
Change from baseline in Kidney Disease Quality of Life-Short Form (KDQOL-SF)
Time frame: Week 24
Population: Due to difficulties enrolling appropriate Focal Segmental Glomerulosclerosis (FSGS) patients, Aurinia terminated the clinical trial early. Focal Segmental Glomerulosclerosis (FSGS) is a rare disease with an estimated 40,000 adult patients in the USA. Only five subjects were enrolled into the clinical trial. The primary and secondary endpoints were not assessed due to insufficient data collected.
Secondary
Renal Biopsy
Descriptive analyses of changes in histopathology will be evaluated in post treatment renal biopsies in a subset of patients
Time frame: 24 weeks
Population: Due to difficulties enrolling appropriate Focal Segmental Glomerulosclerosis (FSGS) patients, Aurinia terminated the clinical trial early. Focal Segmental Glomerulosclerosis (FSGS) is a rare disease with an estimated 40,000 adult patients in the USA. Only five subjects were enrolled into the clinical trial. The primary and secondary endpoints were not assessed due to insufficient data collected.
Secondary
Safety and Tolerability (Treatment-Emergent Adverse Events)
Incidence and number of treatment-emergent adverse events
Time frame: 24 weeks
Population: Due to difficulties enrolling appropriate Focal Segmental Glomerulosclerosis (FSGS) patients, Aurinia terminated the clinical trial early. Focal Segmental Glomerulosclerosis (FSGS) is a rare disease with an estimated 40,000 adult patients in the USA. Only five subjects were enrolled into the clinical trial. The primary and secondary endpoints were not assessed due to insufficient data collected.
Secondary
Time to First Occurrence of 50% Reduction in Urine Protein Creatinine Ratio (UPCR) From Baseline
50% reduction in Urine Protein Creatinine Ratio (UPCR) from baseline
Time frame: Up to 26 weeks
Population: Due to difficulties enrolling appropriate Focal Segmental Glomerulosclerosis (FSGS) patients, Aurinia terminated the clinical trial early. Focal Segmental Glomerulosclerosis (FSGS) is a rare disease with an estimated 40,000 adult patients in the USA. Only five subjects were enrolled into the clinical trial. The primary and secondary endpoints were not assessed due to insufficient data collected.
Secondary
Time to First Occurrence of Complete or Partial Remission of Proteinuria
Complete OR partial remission of proteinuria
Time frame: Up to 26 weeks
Population: Due to difficulties enrolling appropriate Focal Segmental Glomerulosclerosis (FSGS) patients, Aurinia terminated the clinical trial early. Focal Segmental Glomerulosclerosis (FSGS) is a rare disease with an estimated 40,000 adult patients in the USA. Only five subjects were enrolled into the clinical trial. The primary and secondary endpoints were not assessed due to insufficient data collected.
Secondary
Time to First Occurrence of Complete Remission of Proteinuria
Complete remission of proteinuria
Time frame: Up to 26 weeks
Population: Due to difficulties enrolling appropriate Focal Segmental Glomerulosclerosis (FSGS) patients, Aurinia terminated the clinical trial early. Focal Segmental Glomerulosclerosis (FSGS) is a rare disease with an estimated 40,000 adult patients in the USA. Only five subjects were enrolled into the clinical trial. The primary and secondary endpoints were not assessed due to insufficient data collected.
Secondary
Time to First Occurrence of Partial Remission of Proteinuria
Partial remission of proteinuria
Time frame: Up to 26 weeks
Population: Due to difficulties enrolling appropriate Focal Segmental Glomerulosclerosis (FSGS) patients, Aurinia terminated the clinical trial early. Focal Segmental Glomerulosclerosis (FSGS) is a rare disease with an estimated 40,000 adult patients in the USA. Only five subjects were enrolled into the clinical trial. The primary and secondary endpoints were not assessed due to insufficient data collected.