Aurinia Renal Assessments 2: Aurinia Renal Response in Lupus With Voclosporin

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Lupus Nephritis

Intervention / Treatment
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* Drug: Voclosporin
* Drug: Placebo Oral Capsule


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. Written informed consent before any study-specific procedures were performed. In the opinion of the investigator, subject required continued immunosuppressive therapy. Women of childbearing potential must continue to use effective contraception and have a negative urine pregnancy test at Month 12. Subject is willing to continue taking oral mycophenolate mofetil (MMF) for the duration of the study. Exclusion Criteria: 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. Subjects currently requiring renal dialysis (hemodialysis or peritoneal dialysis) or expected to require dialysis during the study period. A planned kidney transplant within study treatment period. 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. Subjects who are pregnant, breast feeding or, if of childbearing potential, not using adequate contraceptive precautions. Vaccines using live organisms, virus or bacterial, while taking the study treatment.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Voclosporin<br>Voclosporin | Drug: Voclosporin<br>* Calcineurin inhibitor, oral, 23.7 mg twice daily (BID)<br>* Other names: ISA247;|
| Placebo Comparator: Placebo Oral Capsule<br>Placebo | Drug: Placebo Oral Capsule<br>* Voclosporin placebo, oral, 3 capsules twice daily (BID)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events (AE) Profile and Routine Biochemical and Hematological Assessments. | 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. | Month 12 (AURORA 2 baseline) to Month 36 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number (and Percent) of Subjects in Renal Response | 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. | Months 12 (AURORA 2 Baseline), 18, 24, 30 and 36 | 
| Number (and Percent) of Subjects in Partial Renal Response | Partial renal response defined as a 50% reduction from baseline in urine protein creatinine ratio (UPCR). | Months 12 (AURORA 2 baseline), 18, 24, 30 and 36 | 
| Renal Flare as Adjudicated by the Clinical Endpoints Committee (CEC). | 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 | Month 12 (AURORA 2 baseline) to Month 36 | 
| 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) | 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. | Months 18, 24 and 36 | 
| Change From AURORA 1 Baseline (i.e., Month 0) in Urine Protein to Creatinine Ratio (UPCR) | 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. | Months 12 (AURORA 2 baseline), 18, 24, 30 and 36 | 
| Change From AURORA 1 Baseline (i.e., Month 0) in Estimated Glomerular Filtration Rate (eGFR) | 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. | Months 12 (AURORA 2 baseline), 18, 24, 30 and 36 | 
| Change From AURORA 1 Baseline (i.e., Month 0) in Urine Protein | 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. | Months 12 (AURORA 2 baseline), 18, 24, 30 and 36 | 
| Change From AURORA 1 Baseline (i.e., Month 0) in Serum Creatinine (SCr) | 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. | Months 12 (AURORA 2 baseline), 18, 24, 30 and 36 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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lupus nephritis, calcineurin inhibitors, voclosporin