Dose-Exploration Evaluating the Efficacy and Safety of Voclosporin in Subjects With Focal Segmental Glomerulosclerosis (AURONA™)
Primary Purpose
Focal Segmental Glomerulosclerosis
Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Voclosporin
Sponsored by
About this trial
This is an interventional treatment trial for Focal Segmental Glomerulosclerosis focused on measuring calcineurin inhibitors, Focal Segmental Glomerulosclerosis
Eligibility Criteria
Inclusion Criteria:
- Primary FSGS diagnosed by renal biopsy.
- 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.
- Stable proteinuria, renal function, and BP.
Exclusion Criteria:
- Clinical or histologic evidence of secondary FSGS.
- Histologic evidence of collapsing variant FSGS.
- 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.
- Currently requiring renal dialysis (hemodialysis or peritoneal dialysis) or expected to require dialysis during the study period.
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.
Sites / Locations
- FSGS Investigative Center
- FSGS Investigative Center
- FSGS Investigative Center
- FSGS Investigative Center
- FSGS Investigative Center
- FSGS Investigative Center
- FSGS Investigative Center
- FSGS Investigative Center
- FSGS Investigative Center
- FSGS Investigative Centre
- FSGS Investigative Center
- FSGS Investigative Center
- FSGS Investigative Center
- FSGS Investigative Center
- FSGS Investigative Center
- FSGS Investigative Center
- FSGS Investigative Center
- FSGS Investigative Center
- FSGS Investigative Center
- FSGS Investigative Center
- FSGS Investigative Site
- FSGS Investigative Centre
- FSGS Investigative Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Voclosporin
Arm Description
Cohort 1: Maximum dose of 3 capsules (7.9mg) BID Cohort 2 Dosing to be decided based on the safety from the first 5 or 6 subjects in Cohort 1.
Outcomes
Primary Outcome Measures
Proportion of Subjects With Remission of Proteinuria
Complete remission OR Partial remission
Secondary Outcome Measures
Proportion of Subjects With Complete Remission or Partial Remission of Proteinuria
Complete remission or partial remission of proteinuria
Proportion of Subjects With Complete Remission of Proteinuria
Complete remission of proteinuria
Proportion of Subjects With Reduction of Proteinuria
Reduction of proteinuria
Proportion of Subjects With Partial Remission of Proteinuria
Partial remission of proteinuria
Time to First Occurrence of Complete or Partial Remission of Proteinuria
Complete OR partial remission of proteinuria
Time to First Occurrence of Complete Remission of Proteinuria
Complete remission of proteinuria
Time to First Occurrence of Partial Remission of Proteinuria
Partial remission of proteinuria
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
Duration of Reduced Urine Protein Creatinine Ratio (UPCR)
Duration of reduced Urine Protein Creatinine Ratio (UPCR)
Change From Baseline in Urine Protein Creatinine Ratio (UPCR)
Change from baseline in Urine Protein Creatinine Ratio (UPCR)
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
Proportion of Subjects With a Confirmed Increase in Estimated Glomerular Filtration Rate (eGFR)
Increase in Estimated Glomerular Filtration Rate (eGFR)
Change in Urine Protein Creatinine Ratio (UPCR)
Change in Urine Protein Creatinine Ratio (UPCR)
Change in Estimated Glomerular Filtration Rate (eGFR)
Change in estimated Glomerular Filtration Rate (eGFR)
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)
Quality of Life Assessments
Mean change in Patient Reported Outcome Measurement Information System (PROMIS) measures
Quality of Life Assessments
Change from baseline in Kidney Disease Quality of Life-Short Form (KDQOL-SF)
Safety and Tolerability (Treatment-Emergent Adverse Events)
Incidence and number of treatment-emergent adverse events
Renal Biopsy
Descriptive analyses of changes in histopathology will be evaluated in post treatment renal biopsies in a subset of patients
Full Information
NCT ID
NCT03598036
First Posted
June 14, 2018
Last Updated
August 20, 2021
Sponsor
Aurinia Pharmaceuticals Inc.
1. Study Identification
Unique Protocol Identification Number
NCT03598036
Brief Title
Dose-Exploration Evaluating the Efficacy and Safety of Voclosporin in Subjects With Focal Segmental Glomerulosclerosis
Acronym
AURONA™
Official Title
An Open-Label Dose-Exploration Cohort Study Evaluating the Efficacy and Safety of Voclosporin in Achieving Complete or Partial Remission of Proteinuria in Subjects With Focal Segmental Glomerulosclerosis
Study Type
Interventional
2. Study Status
Record Verification Date
June 2020
Overall Recruitment Status
Terminated
Why Stopped
Low recruitment rate
Study Start Date
June 21, 2018 (Actual)
Primary Completion Date
May 19, 2020 (Actual)
Study Completion Date
May 19, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Aurinia Pharmaceuticals Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Focal Segmental Glomerulosclerosis
Keywords
calcineurin inhibitors, Focal Segmental Glomerulosclerosis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
5 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Voclosporin
Arm Type
Experimental
Arm Description
Cohort 1:
Maximum dose of 3 capsules (7.9mg) BID
Cohort 2
Dosing to be decided based on the safety from the first 5 or 6 subjects in Cohort 1.
Intervention Type
Drug
Intervention Name(s)
Voclosporin
Intervention Description
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.
Primary Outcome Measure Information:
Title
Proportion of Subjects With Remission of Proteinuria
Description
Complete remission OR Partial remission
Time Frame
24 weeks
Secondary Outcome Measure Information:
Title
Proportion of Subjects With Complete Remission or Partial Remission of Proteinuria
Description
Complete remission or partial remission of proteinuria
Time Frame
Weeks 8 and 12
Title
Proportion of Subjects With Complete Remission of Proteinuria
Description
Complete remission of proteinuria
Time Frame
Weeks 8, 12, and 24
Title
Proportion of Subjects With Reduction of Proteinuria
Description
Reduction of proteinuria
Time Frame
Weeks 8, 12, and 24
Title
Proportion of Subjects With Partial Remission of Proteinuria
Description
Partial remission of proteinuria
Time Frame
Weeks 8, 12, and 24
Title
Time to First Occurrence of Complete or Partial Remission of Proteinuria
Description
Complete OR partial remission of proteinuria
Time Frame
Up to 26 weeks
Title
Time to First Occurrence of Complete Remission of Proteinuria
Description
Complete remission of proteinuria
Time Frame
Up to 26 weeks
Title
Time to First Occurrence of Partial Remission of Proteinuria
Description
Partial remission of proteinuria
Time Frame
Up to 26 weeks
Title
Time to First Occurrence of 50% Reduction in Urine Protein Creatinine Ratio (UPCR) From Baseline
Description
50% reduction in Urine Protein Creatinine Ratio (UPCR) from baseline
Time Frame
Up to 26 weeks
Title
Duration of Reduced Urine Protein Creatinine Ratio (UPCR)
Description
Duration of reduced Urine Protein Creatinine Ratio (UPCR)
Time Frame
Up to 26 weeks
Title
Change From Baseline in Urine Protein Creatinine Ratio (UPCR)
Description
Change from baseline in Urine Protein Creatinine Ratio (UPCR)
Time Frame
Weeks 2,4,8,12,18,24
Title
Proportion of Subjects With a Confirmed Decrease From Baseline in Estimated Glomerular Filtration Rate (eGFR)
Description
Utilizing the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) formula
Time Frame
Weeks 2,4,8,12,18,24
Title
Proportion of Subjects With a Confirmed Increase in Estimated Glomerular Filtration Rate (eGFR)
Description
Increase in Estimated Glomerular Filtration Rate (eGFR)
Time Frame
Week 24 to Week 26
Title
Change in Urine Protein Creatinine Ratio (UPCR)
Description
Change in Urine Protein Creatinine Ratio (UPCR)
Time Frame
Week 24 and Week 26
Title
Change in Estimated Glomerular Filtration Rate (eGFR)
Description
Change in estimated Glomerular Filtration Rate (eGFR)
Time Frame
Week 24 and Week 26
Title
Change From Baseline in Serum Creatinine, Serum Albumin and Estimate Glomerular Filtration Rate (eGFR)
Description
Change from baseline in serum creatinine, serum albumin and estimate Glomerular Filtration Rate (eGFR)
Time Frame
Weeks 2,4,8,12,18,24
Title
Quality of Life Assessments
Description
Mean change in Patient Reported Outcome Measurement Information System (PROMIS) measures
Time Frame
Week 24
Title
Quality of Life Assessments
Description
Change from baseline in Kidney Disease Quality of Life-Short Form (KDQOL-SF)
Time Frame
Week 24
Title
Safety and Tolerability (Treatment-Emergent Adverse Events)
Description
Incidence and number of treatment-emergent adverse events
Time Frame
24 weeks
Title
Renal Biopsy
Description
Descriptive analyses of changes in histopathology will be evaluated in post treatment renal biopsies in a subset of patients
Time Frame
24 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Primary FSGS diagnosed by renal biopsy.
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.
Stable proteinuria, renal function, and BP.
Exclusion Criteria:
Clinical or histologic evidence of secondary FSGS.
Histologic evidence of collapsing variant FSGS.
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.
Currently requiring renal dialysis (hemodialysis or peritoneal dialysis) or expected to require dialysis during the study period.
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.
Facility Information:
Facility Name
FSGS Investigative Center
City
Denver
State/Province
Colorado
ZIP/Postal Code
80213
Country
United States
Facility Name
FSGS Investigative Center
City
Winter Park
State/Province
Florida
ZIP/Postal Code
32789
Country
United States
Facility Name
FSGS Investigative Center
City
Lawrenceville
State/Province
Georgia
ZIP/Postal Code
30046
Country
United States
Facility Name
FSGS Investigative Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
FSGS Investigative Center
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Facility Name
FSGS Investigative Center
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40202
Country
United States
Facility Name
FSGS Investigative Center
City
Shreveport
State/Province
Louisiana
ZIP/Postal Code
71101
Country
United States
Facility Name
FSGS Investigative Center
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
FSGS Investigative Center
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55414
Country
United States
Facility Name
FSGS Investigative Centre
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
FSGS Investigative Center
City
Newark
State/Province
New Jersey
ZIP/Postal Code
07103
Country
United States
Facility Name
FSGS Investigative Center
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
FSGS Investigative Center
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599-7155
Country
United States
Facility Name
FSGS Investigative Center
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28204
Country
United States
Facility Name
FSGS Investigative Center
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
FSGS Investigative Center
City
Bethlehem
State/Province
Pennsylvania
ZIP/Postal Code
18017
Country
United States
Facility Name
FSGS Investigative Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75231
Country
United States
Facility Name
FSGS Investigative Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75246
Country
United States
Facility Name
FSGS Investigative Center
City
El Paso
State/Province
Texas
ZIP/Postal Code
79935
Country
United States
Facility Name
FSGS Investigative Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
FSGS Investigative Site
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84115
Country
United States
Facility Name
FSGS Investigative Centre
City
Santiago De Los Caballeros
ZIP/Postal Code
51000
Country
Dominican Republic
Facility Name
FSGS Investigative Center
City
Santo Domingo
Country
Dominican Republic
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
24330024
Citation
Ling SY, Huizinga RB, Mayo PR, Larouche R, Freitag DG, Aspeslet LJ, Foster RT. Cytochrome P450 3A and P-glycoprotein drug-drug interactions with voclosporin. Br J Clin Pharmacol. 2014 Jun;77(6):1039-50. doi: 10.1111/bcp.12309.
Results Reference
background
PubMed Identifier
23996158
Citation
Ling SY, Huizinga RB, Mayo PR, Freitag DG, Aspeslet LJ, Foster RT. Pharmacokinetics of voclosporin in renal impairment and hepatic impairment. J Clin Pharmacol. 2013 Dec;53(12):1303-12. doi: 10.1002/jcph.166. Epub 2013 Oct 8.
Results Reference
background
PubMed Identifier
23736966
Citation
Mayo PR, Huizinga RB, Ling SY, Freitag DG, Aspeslet LJ, Foster RT. Voclosporin food effect and single oral ascending dose pharmacokinetic and pharmacodynamic studies in healthy human subjects. J Clin Pharmacol. 2013 Aug;53(8):819-26. doi: 10.1002/jcph.114. Epub 2013 Jun 4.
Results Reference
background
PubMed Identifier
21943027
Citation
Busque S, Cantarovich M, Mulgaonkar S, Gaston R, Gaber AO, Mayo PR, Ling S, Huizinga RB, Meier-Kriesche HU; PROMISE Investigators. The PROMISE study: a phase 2b multicenter study of voclosporin (ISA247) versus tacrolimus in de novo kidney transplantation. Am J Transplant. 2011 Dec;11(12):2675-84. doi: 10.1111/j.1600-6143.2011.03763.x. Epub 2011 Sep 22.
Results Reference
background
Learn more about this trial
Dose-Exploration Evaluating the Efficacy and Safety of Voclosporin in Subjects With Focal Segmental Glomerulosclerosis
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