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

Phase 2

Terminated

• Conditions: Focal Segmental Glomerulosclerosis
• Interventions: Drug: Voclosporin

• Registration Number: NCT03598036
• Lead Sponsor: Aurinia Pharmaceuticals Inc.

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.

Study Timeline

• Study First Submitted: 2018-06-14
• Study Start: 2018-06-21
• Study First Submitted QC: 2018-07-24
• Study First Posted: 2018-07-26
• Primary Completion: 2020-05-19
• Study Completion: 2020-05-19
• Status Verified: 2020-06
• Results First Submitted: 2021-05-17
• Results First Submitted QC: 2021-08-20
• Last Update Submitted: 2021-08-20
• Results First Posted: 2021-09-16
• Last Update Posted: 2021-09-16

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 5

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Voclosporin	Voclosporin	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.

Primary Outcome Measures

Name	Time	Method
Proportion of Subjects With Remission of Proteinuria	24 weeks	Complete remission OR Partial remission

Secondary Outcome Measures

Name	Time	Method
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
Proportion of Subjects With Partial Remission of Proteinuria	Weeks 8, 12, and 24	Partial remission of proteinuria
Time to First Occurrence of Complete or Partial Remission of Proteinuria	Up to 26 weeks	Complete OR 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
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)
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)
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	Change from baseline in Kidney Disease Quality of Life-Short Form (KDQOL-SF)
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

Trial Locations

Locations (3)

FSGS Investigative Center; 🇩🇴 Santo Domingo, Dominican Republic

FSGS Investigative Site; 🇺🇸 Salt Lake City, Utah, United States

FSGS Investigative Centre; 🇩🇴 Santiago De Los Caballeros, Dominican Republic