Aurinia Renal Assessments 2: Aurinia Renal Response in Lupus With Voclosporin (AURORA 2)

• ClinicalTrials.gov Identifier: NCT03597464
• Recruitment Status: Completed
• First Posted: July 24, 2018
• Results First Posted: December 14, 2022
• Last Update Posted: December 14, 2022
• Sponsor: Aurinia Pharmaceuticals Inc.
• Information provided by (Responsible Party): Aurinia Pharmaceuticals Inc.

Study Description

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).

Condition or disease	Intervention/treatment	Phase
Lupus Nephritis	Drug: Voclosporin; Drug: Placebo Oral Capsule	Phase 3

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 216 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: September 29, 2019
• Actual Primary Completion Date: October 7, 2021
• Actual Study Completion Date: October 7, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: Voclosporin; Voclosporin	Drug: Voclosporin; Calcineurin inhibitor, oral, 23.7 mg twice daily (BID); Other Name: ISA247
Placebo Comparator: Placebo Oral Capsule; Placebo	Drug: Placebo Oral Capsule; Voclosporin placebo, oral, 3 capsules twice daily (BID)

Outcome Measures

Primary Outcome Measures :

1. Adverse Events (AE) Profile and Routine Biochemical and Hematological Assessments. [ Time Frame: Month 12 (AURORA 2 baseline) to Month 36 ]

   Number (and percent) of adverse events experienced during the AURORA 2 treatment period.

   To 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 LN.

Secondary Outcome Measures :

1. Number (and Percent) of Subjects in Renal Response [ Time Frame: Months 12 (AURORA 2 Baseline), 18, 24, 30 and 36 ]

   Proportion of subjects in renal response defined as:

   • urine protein creatinine ratio (UPCR) of ≤0.5 mg/mg
   • estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m^2 or no confirmed decrease from baseline in eGFR of >20%
   • Received no rescue medication for LN
   • Did not receive more than 10 mg prednisone for ≥3 consecutive days or for ≥7 days in total during the 8 weeks prior to the renal response assessment.
2. Number (and Percent) of Subjects in Partial Renal Response [ Time Frame: Months 12 (AURORA 2 baseline), 18, 24, 30 and 36 ]
   Partial renal response defined as a 50% reduction from baseline in urine protein creatinine ratio (UPCR).
3. Renal Flare as Adjudicated by the Clinical Endpoints Committee (CEC). [ Time Frame: Month 12 (AURORA 2 baseline) to Month 36 ]

   A patient could experience a flare from the point they achieved a response (or recovery). Renal flares were judged according to the following criteria:

   • A reproducible increase to UPCR >1 mg/mg from a post-response baseline of <0.2 mg/mg or
   • an increase to UPCR >2 mg/mg from a post-response baseline between 0.2 to 1.0 mg/mg or
   • a doubling of UPCR for baseline values of UPCR >1 mg/mg
4. 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) [ Time Frame: Months 18, 24 and 36 ]

   Participants analyzed included all subjects who were randomized treatment during AURORA 1 AND who consented to continue their treatment in AURORA 2. Baseline values were collected at the start of AURORA 1 but only for those subjects that continued in AURORA 2.

   Assessment of Systemic Lupus Erythematosus (SLE) Disease Activity within the last 10 days. It scores 24 disease descriptors across 9 organ systems which are summed to a minimum of <2 (considered indicative of no activity) and maximum of 105 points. Scores are weighted and a score of 6 is considered clinically significant. Higher scores indicate worse disease activity.

5. Change From AURORA 1 Baseline (i.e., Month 0) in Urine Protein to Creatinine Ratio (UPCR) [ Time Frame: Months 12 (AURORA 2 baseline), 18, 24, 30 and 36 ]

   Participants analyzed included all subjects who were randomized treatment during AURORA 1 AND who consented to continue their treatment in AURORA 2. Baseline values were collected at the start of AURORA 1 but only for those subjects that continued in AURORA 2.

   Reductions in UPCR are indicative of better renal outcomes.

6. Change From AURORA 1 Baseline (i.e., Month 0) in Estimated Glomerular Filtration Rate (eGFR) [ Time Frame: Months 12 (AURORA 2 baseline), 18, 24, 30 and 36 ]

   Participants analyzed included all subjects who were randomized treatment during AURORA 1 AND who consented to continue their treatment in AURORA 2. Baseline values were collected at the start of AURORA 1 but only for those subjects that continued in AURORA 2.

   This endpoint incorporated Corrected eGFR values with a ceiling set to 90 mL/min/1.73 m^2

   Increases in eGFR levels are indicative of better renal outcomes.

7. Change From AURORA 1 Baseline (i.e., Month 0) in Urine Protein [ Time Frame: Months 12 (AURORA 2 baseline), 18, 24, 30 and 36 ]

   Participants analyzed included all subjects who were randomized treatment during AURORA 1 AND who consented to continue their treatment in AURORA 2. Baseline values were collected at the start of AURORA 1 but only for those subjects that continued in AURORA 2.

   Reductions in Urine Protein levels are indicative of better renal outcomes.

8. Change From AURORA 1 Baseline (i.e., Month 0) in Serum Creatinine (SCr) [ Time Frame: Months 12 (AURORA 2 baseline), 18, 24, 30 and 36 ]

   Participants analyzed included all subjects who were randomized treatment during AURORA 1 AND who consented to continue their treatment in AURORA 2. Baseline values were collected at the start of AURORA 1 but only for those subjects that continued in AURORA 2.

   Decreases in SCr levels can be indicative of better renal outcomes.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

United States, Oklahoma

AURORA Investigative Center

Oklahoma City, Oklahoma, United States, 73104

Sponsors and Collaborators

Aurinia Pharmaceuticals Inc.

  Study Documents (Full-Text)

Documents provided by Aurinia Pharmaceuticals Inc.:

Study Protocol: Protocol v1.0  [PDF] October 13, 2017

Study Protocol: Protocol v2.0  [PDF] October 10, 2018

Study Protocol: Protocol v3.0  [PDF] December 21, 2018

Statistical Analysis Plan  [PDF] May 11, 2021

More Information

Publications:

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.

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.

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.

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.

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.

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.

• Responsible Party: Aurinia Pharmaceuticals Inc.
• ClinicalTrials.gov Identifier: NCT03597464
• Other Study ID Numbers: AUR-VCS-2016-02
• First Posted: July 24, 2018
• Results First Posted: December 14, 2022
• Last Update Posted: December 14, 2022
• Last Verified: November 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Aurinia Pharmaceuticals Inc.:

lupus nephritis; calcineurin inhibitors; voclosporin

Additional relevant MeSH terms:

Nephritis; Lupus Nephritis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Glomerulonephritis; Lupus Erythematosus, Systemic; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases