Dose-Exploration Evaluating the Efficacy and Safety of Voclosporin in Subjects With Focal Segmental Glomerulosclerosis

Study Overview
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Brief Summary
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Evaluating the Efficacy and Safety of Voclosporin in Achieving Complete or Partial Remission of Proteinuria in Subjects with Focal Segmental Glomerulosclerosis

Detailed Description
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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.

Official Title
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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

Conditions
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Focal Segmental Glomerulosclerosis

Intervention / Treatment
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* Drug: Voclosporin


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Voclosporin<br>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. | Drug: Voclosporin<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Subjects With Remission of Proteinuria | Complete remission OR Partial remission | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Subjects With Complete Remission or Partial Remission of Proteinuria | Complete remission or partial remission of proteinuria | Weeks 8 and 12 | 
| Proportion of Subjects With Complete Remission of Proteinuria | Complete remission of proteinuria | Weeks 8, 12, and 24 | 
| Proportion of Subjects With Reduction of Proteinuria | Reduction of proteinuria | Weeks 8, 12, and 24 | 
| Proportion of Subjects With Partial Remission of Proteinuria | Partial remission of proteinuria | Weeks 8, 12, and 24 | 
| Time to First Occurrence of Complete or Partial Remission of Proteinuria | Complete OR partial remission of proteinuria | Up to 26 weeks | 
| Time to First Occurrence of Complete Remission of Proteinuria | Complete remission of proteinuria | Up to 26 weeks | 
| Time to First Occurrence of Partial Remission of Proteinuria | Partial remission of proteinuria | Up to 26 weeks | 
| 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 | Up to 26 weeks | 
| Duration of Reduced Urine Protein Creatinine Ratio (UPCR) | Duration of reduced Urine Protein Creatinine Ratio (UPCR) | Up to 26 weeks | 
| Change From Baseline in Urine Protein Creatinine Ratio (UPCR) | Change from baseline in Urine Protein Creatinine Ratio (UPCR) | Weeks 2,4,8,12,18,24 | 
| 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 | Weeks 2,4,8,12,18,24 | 
| Proportion of Subjects With a Confirmed Increase in Estimated Glomerular Filtration Rate (eGFR) | Increase in Estimated Glomerular Filtration Rate (eGFR) | Week 24 to Week 26 | 
| Change in Urine Protein Creatinine Ratio (UPCR) | Change in Urine Protein Creatinine Ratio (UPCR) | Week 24 and Week 26 | 
| Change in Estimated Glomerular Filtration Rate (eGFR) | Change in estimated Glomerular Filtration Rate (eGFR) | Week 24 and Week 26 | 
| 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) | Weeks 2,4,8,12,18,24 | 
| Quality of Life Assessments | Mean change in Patient Reported Outcome Measurement Information System (PROMIS) measures | Week 24 | 
| Quality of Life Assessments | Change from baseline in Kidney Disease Quality of Life-Short Form (KDQOL-SF) | Week 24 | 
| Safety and Tolerability (Treatment-Emergent Adverse Events) | Incidence and number of treatment-emergent adverse events | 24 weeks | 
| Renal Biopsy | Descriptive analyses of changes in histopathology will be evaluated in post treatment renal biopsies in a subset of patients | 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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calcineurin inhibitors, Focal Segmental Glomerulosclerosis