Clinical trial NCT03597464: Aurinia Renal Assessments 2: Aurinia Renal Response in Lupus With Voclosporin
Official title: A Randomized, Controlled, Double-blind, Continuation Study Comparing the Long-term Safety and Efficacy of Voclosporin (23.7 mg Twice Daily) With Placebo in Subjects With Lupus Nephritis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Lupus Nephritis
Keywords: lupus nephritis
calcineurin inhibitors
voclosporin
Lead sponsor: Aurinia Pharmaceuticals Inc.
Sponsor class: INDUSTRY
First posted: 2018-07-24
Enrollment: 216
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is assess the long-term safety and tolerability of voclosporin compared with placebo for up to an additional 24 months following completion of treatment in the AURORA 1 study in subjects with lupus nephritis (LN).

Detailed description: The aim of the Phase 3 continuation study (AURORA 2) is to assess the long-term safety and tolerability of voclosporin, added to the standard of care treatment in LN, for an additional 24 months, following a treatment period of 52 weeks in the AURORA 1 study (AUR-VCS-2016-01). All subjects will continue to receive background therapy of mycophenolate mofetil (MMF) and/or oral corticosteroids starting at the same dose as at the end of the AURORA 1 study. Subjects with LN, who have completed 52 weeks of treatment with study drug in the AURORA 1 study, will be eligible to enter the study. The long-term safety and tolerability of the drug combination will be assessed from its safety profile while demonstrating the continued ability to achieve and maintain long-term renal response.

Eligibility criteria: Inclusion Criteria:

1. Subjects who have completed 52 weeks of treatment with study drug in the AURORA 1 study. Subjects who had a temporary interruption and successfully restarted study drug during the AURORA 1 study will be allowed with Medical Monitor approval.
2. Written informed consent before any study-specific procedures were performed.
3. In the opinion of the investigator, subject required continued immunosuppressive therapy.
4. Women of childbearing potential must continue to use effective contraception and have a negative urine pregnancy test at Month 12.
5. Subject is willing to continue taking oral mycophenolate mofetil (MMF) for the duration of the study.

Exclusion Criteria:

1. Currently taking or known need for any of the medications or food items listed in Section 7.8, Prohibited Therapy and Concomitant Treatment during the study.
2. Subjects currently requiring renal dialysis (hemodialysis or peritoneal dialysis) or expected to require dialysis during the study period.
3. A planned kidney transplant within study treatment period.
4. Subjects with any medical condition which, in the Investigator's judgment, may be associated with increased risk to the subject or may interfere with study assessments or outcomes.
5. Subjects who are pregnant, breast feeding or, if of childbearing potential, not using adequate contraceptive precautions.
6. Vaccines using live organisms, virus or bacterial, while taking the study treatment.

Primary outcomes:
measure: Adverse Events (AE) Profile and Routine Biochemical and Hematological Assessments.
timeFrame: Month 12 (AURORA 2 baseline) to Month 36
Secondary outcomes:
measure: Number (and Percent) of Subjects in Renal Response
timeFrame: Months 12 (AURORA 2 Baseline), 18, 24, 30 and 36
measure: Number (and Percent) of Subjects in Partial Renal Response
timeFrame: Months 12 (AURORA 2 baseline), 18, 24, 30 and 36
measure: Renal Flare as Adjudicated by the Clinical Endpoints Committee (CEC).
timeFrame: Month 12 (AURORA 2 baseline) to Month 36
measure: Change From AURORA 1 Baseline (i.e., Month 0) in Safety of Estrogens in Lupus Erythematosus National Assessment Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI)
timeFrame: Months 18, 24 and 36
measure: Change From AURORA 1 Baseline (i.e., Month 0) in Urine Protein to Creatinine Ratio (UPCR)
timeFrame: Months 12 (AURORA 2 baseline), 18, 24, 30 and 36
measure: Change From AURORA 1 Baseline (i.e., Month 0) in Estimated Glomerular Filtration Rate (eGFR)
timeFrame: Months 12 (AURORA 2 baseline), 18, 24, 30 and 36
measure: Change From AURORA 1 Baseline (i.e., Month 0) in Urine Protein
timeFrame: Months 12 (AURORA 2 baseline), 18, 24, 30 and 36
measure: Change From AURORA 1 Baseline (i.e., Month 0) in Serum Creatinine (SCr)
timeFrame: Months 12 (AURORA 2 baseline), 18, 24, 30 and 36
Other outcomes:
Locations:
city: Oklahoma City
country: United States
facility: AURORA Investigative Center
state: Oklahoma
Study officials:
References:
citation: Rovin BH, Parikh SV, Hebert LA, Chan TM, Mok CC, Ginzler EM, Hooi LS, Brunetta P, Maciuca R, Solomons N. Lupus nephritis: induction therapy in severe lupus nephritis--should MMF be considered the drug of choice? Clin J Am Soc Nephrol. 2013 Jan;8(1):147-53. doi: 10.2215/CJN.03290412. Epub 2012 Aug 9.
citation: Dooley MA, Jayne D, Ginzler EM, Isenberg D, Olsen NJ, Wofsy D, Eitner F, Appel GB, Contreras G, Lisk L, Solomons N; ALMS Group. Mycophenolate versus azathioprine as maintenance therapy for lupus nephritis. N Engl J Med. 2011 Nov 17;365(20):1886-95. doi: 10.1056/NEJMoa1014460.
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.