Clinical trial NCT03598036: Dose-Exploration Evaluating the Efficacy and Safety of Voclosporin in Subjects With Focal Segmental Glomerulosclerosis
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
Overall status: TERMINATED
Phase: PHASE2
Conditions: Focal Segmental Glomerulosclerosis
Keywords: calcineurin inhibitors
Focal Segmental Glomerulosclerosis
Lead sponsor: Aurinia Pharmaceuticals Inc.
Sponsor class: INDUSTRY
First posted: 2018-07-26
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Proportion of Subjects With Remission of Proteinuria
timeFrame: 24 weeks
Secondary outcomes:
measure: Proportion of Subjects With Complete Remission or Partial Remission of Proteinuria
timeFrame: Weeks 8 and 12
measure: Proportion of Subjects With Complete Remission of Proteinuria
timeFrame: Weeks 8, 12, and 24
measure: Proportion of Subjects With Reduction of Proteinuria
timeFrame: Weeks 8, 12, and 24
measure: Proportion of Subjects With Partial Remission of Proteinuria
timeFrame: Weeks 8, 12, and 24
measure: Time to First Occurrence of Complete or Partial Remission of Proteinuria
timeFrame: Up to 26 weeks
measure: Time to First Occurrence of Complete Remission of Proteinuria
timeFrame: Up to 26 weeks
measure: Time to First Occurrence of Partial Remission of Proteinuria
timeFrame: Up to 26 weeks
measure: Time to First Occurrence of 50% Reduction in Urine Protein Creatinine Ratio (UPCR) From Baseline
timeFrame: Up to 26 weeks
measure: Duration of Reduced Urine Protein Creatinine Ratio (UPCR)
timeFrame: Up to 26 weeks
measure: Change From Baseline in Urine Protein Creatinine Ratio (UPCR)
timeFrame: Weeks 2,4,8,12,18,24
measure: Proportion of Subjects With a Confirmed Decrease From Baseline in Estimated Glomerular Filtration Rate (eGFR)
timeFrame: Weeks 2,4,8,12,18,24
measure: Proportion of Subjects With a Confirmed Increase in Estimated Glomerular Filtration Rate (eGFR)
timeFrame: Week 24 to Week 26
measure: Change in Urine Protein Creatinine Ratio (UPCR)
timeFrame: Week 24 and Week 26
measure: Change in Estimated Glomerular Filtration Rate (eGFR)
timeFrame: Week 24 and Week 26
measure: Change From Baseline in Serum Creatinine, Serum Albumin and Estimate Glomerular Filtration Rate (eGFR)
timeFrame: Weeks 2,4,8,12,18,24
measure: Quality of Life Assessments
timeFrame: Week 24
measure: Quality of Life Assessments
timeFrame: Week 24
measure: Safety and Tolerability (Treatment-Emergent Adverse Events)
timeFrame: 24 weeks
measure: Renal Biopsy
timeFrame: 24 weeks
Other outcomes:
Locations:
city: Denver
country: United States
facility: FSGS Investigative Center
state: Colorado
city: Winter Park
country: United States
facility: FSGS Investigative Center
state: Florida
city: Lawrenceville
country: United States
facility: FSGS Investigative Center
state: Georgia
city: Chicago
country: United States
facility: FSGS Investigative Center
state: Illinois
city: Iowa City
country: United States
facility: FSGS Investigative Center
state: Iowa
city: Louisville
country: United States
facility: FSGS Investigative Center
state: Kentucky
city: Shreveport
country: United States
facility: FSGS Investigative Center
state: Louisiana
city: Detroit
country: United States
facility: FSGS Investigative Center
state: Michigan
city: Minneapolis
country: United States
facility: FSGS Investigative Center
state: Minnesota
city: Saint Louis
country: United States
facility: FSGS Investigative Centre
state: Missouri
city: Newark
country: United States
facility: FSGS Investigative Center
state: New Jersey
city: New York
country: United States
facility: FSGS Investigative Center
state: New York
city: Chapel Hill
country: United States
facility: FSGS Investigative Center
state: North Carolina
city: Charlotte
country: United States
facility: FSGS Investigative Center
state: North Carolina
city: Columbus
country: United States
facility: FSGS Investigative Center
state: Ohio
city: Bethlehem
country: United States
facility: FSGS Investigative Center
state: Pennsylvania
city: Dallas
country: United States
facility: FSGS Investigative Center
state: Texas
city: Dallas
country: United States
facility: FSGS Investigative Center
state: Texas
city: El Paso
country: United States
facility: FSGS Investigative Center
state: Texas
city: Houston
country: United States
facility: FSGS Investigative Center
state: Texas
city: Salt Lake City
country: United States
facility: FSGS Investigative Site
state: Utah
city: Santiago De Los Caballeros
country: Dominican Republic
facility: FSGS Investigative Centre
city: Santo Domingo
country: Dominican Republic
facility: FSGS Investigative Center
Study officials:
References:
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.
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.
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.
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.