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

Focal Segmental Glomerulosclerosis Clinical Trial

— 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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03598036
• Other study ID #: AUR-VCS-2017-03
• Status: Terminated
• Phase: Phase 2
• Start date: June 21, 2018
• Est. completion date: May 19, 2020

Study information

• Verified date: June 2020
• Source: Aurinia Pharmaceuticals Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 5
• Est. completion date: May 19, 2020
• Est. primary completion date: May 19, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Focal Segmental Glomerulosclerosis
• Glomerulosclerosis, Focal Segmental

Intervention

Drug:
• Voclosporin
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.

Locations

Country	Name	City	State
Dominican Republic	FSGS Investigative Centre	Santiago De Los Caballeros
Dominican Republic	FSGS Investigative Center	Santo Domingo
United States	FSGS Investigative Center	Bethlehem	Pennsylvania
United States	FSGS Investigative Center	Chapel Hill	North Carolina
United States	FSGS Investigative Center	Charlotte	North Carolina
United States	FSGS Investigative Center	Chicago	Illinois
United States	FSGS Investigative Center	Columbus	Ohio
United States	FSGS Investigative Center	Dallas	Texas
United States	FSGS Investigative Center	Dallas	Texas
United States	FSGS Investigative Center	Denver	Colorado
United States	FSGS Investigative Center	Detroit	Michigan
United States	FSGS Investigative Center	El Paso	Texas
United States	FSGS Investigative Center	Houston	Texas
United States	FSGS Investigative Center	Iowa City	Iowa
United States	FSGS Investigative Center	Lawrenceville	Georgia
United States	FSGS Investigative Center	Louisville	Kentucky
United States	FSGS Investigative Center	Minneapolis	Minnesota
United States	FSGS Investigative Center	New York	New York
United States	FSGS Investigative Center	Newark	New Jersey
United States	FSGS Investigative Centre	Saint Louis	Missouri
United States	FSGS Investigative Site	Salt Lake City	Utah
United States	FSGS Investigative Center	Shreveport	Louisiana
United States	FSGS Investigative Center	Winter Park	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Aurinia Pharmaceuticals Inc.

Countries where clinical trial is conducted

United States,  Dominican Republic, 

References & Publications (4)

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. — View 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. — View 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. — View 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. — View Citation

Outcome

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