Lupus Nephritis
Conditions
Keywords
lupus nephritis, calcineurin inhibitors, voclosporin
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.
Interventions
DRUGVoclosporin
Calcineurin inhibitor, oral, 23.7 mg twice daily (BID)
DRUGPlacebo Oral Capsule
Voclosporin placebo, oral, 3 capsules twice daily (BID)
Sponsors
Aurinia Pharmaceuticals Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Events (AE) Profile and Routine Biochemical and Hematological Assessments. | 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
| Measure | Time frame | Description |
|---|---|---|
| Number (and Percent) of Subjects in Partial Renal Response | 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). |
| Renal Flare as Adjudicated by the Clinical Endpoints Committee (CEC). | 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 |
| 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) | 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. |
| Number (and Percent) of Subjects in Renal Response | 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. |
| Change From AURORA 1 Baseline (i.e., Month 0) in Estimated Glomerular Filtration Rate (eGFR) | 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. |
| Change From AURORA 1 Baseline (i.e., Month 0) in Urine Protein | 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. |
| Change From AURORA 1 Baseline (i.e., Month 0) in Serum Creatinine (SCr) | 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. |
| Change From AURORA 1 Baseline (i.e., Month 0) in Urine Protein to Creatinine Ratio (UPCR) | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Voclosporin Voclosporin 23.7 mg twice daily (BID) + Mycophenolate Mofetil (MMF) + corticosteroid | 116 |
| Placebo Oral Capsule Placebo 23.7 mg twice daily (BID) + Mycophenolate Mofetil (MMF) + corticosteroid | 100 |
| Total | 216 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 2 |
| Overall Study | Death | 0 | 3 |
| Overall Study | Lack of Efficacy | 2 | 0 |
| Overall Study | Lost to Follow-up | 3 | 1 |
| Overall Study | Physician Decision | 2 | 2 |
| Overall Study | Pregnancy | 3 | 1 |
| Overall Study | Protocol Violation | 1 | 1 |
| Overall Study | Withdrawal by Subject | 4 | 5 |
Baseline characteristics
| Characteristic | Voclosporin | Placebo Oral Capsule | Total |
|---|---|---|---|
| Age, Continuous | 32.3 years STANDARD_DEVIATION 10.31 | 35.4 years STANDARD_DEVIATION 11.64 | 33.7 years STANDARD_DEVIATION 11.03 |
| Baseline estimated glomerular filtration rate (eGFR) | 94.1 mL/min/1.73 m^2 STANDARD_DEVIATION 31.36 | 92.0 mL/min/1.73 m^2 STANDARD_DEVIATION 28.04 | 93.2 mL/min/1.73 m^2 STANDARD_DEVIATION 29.82 |
| Baseline Urine Protein Creatinine Ratio (UPCR) | 3.941 mg/mg STANDARD_DEVIATION 2.5766 | 3.868 mg/mg STANDARD_DEVIATION 2.4764 | 3.907 mg/mg STANDARD_DEVIATION 2.5251 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 39 Participants | 33 Participants | 72 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 77 Participants | 67 Participants | 144 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Lupus Nephritis (LN) history Years since diagnosis of lupus nephritis (LN) | 4.8 years STANDARD_DEVIATION 5.27 | 5.0 years STANDARD_DEVIATION 5.23 | 4.9 years STANDARD_DEVIATION 5.24 |
| Lupus Nephritis (LN) history Years since diagnosis of systemic lupus erythematosus (SLE) | 6.6 years STANDARD_DEVIATION 6.66 | 7.3 years STANDARD_DEVIATION 6.85 | 6.9 years STANDARD_DEVIATION 6.75 |
| Lupus Nephritis (LN) history Years since first instance of significant proteinuria (>500 mg/day) | 5.0 years STANDARD_DEVIATION 5.15 | 4.7 years STANDARD_DEVIATION 4.49 | 4.8 years STANDARD_DEVIATION 4.85 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 30 Participants | 30 Participants | 60 Participants |
| Race (NIH/OMB) Black or African American | 18 Participants | 7 Participants | 25 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 24 Participants | 23 Participants | 47 Participants |
| Race (NIH/OMB) White | 44 Participants | 40 Participants | 84 Participants |
| Region of Enrollment Europe | 38 participants | 37 participants | 75 participants |
| Region of Enrollment South America | 34 participants | 27 participants | 61 participants |
| Region of Enrollment Southeast Asia | 29 participants | 27 participants | 56 participants |
| Region of Enrollment United States | 15 participants | 9 participants | 24 participants |
| Sex: Female, Male Female | 105 Participants | 88 Participants | 193 Participants |
| Sex: Female, Male Male | 11 Participants | 12 Participants | 23 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 116 | 3 / 100 |
| other Total, other adverse events | 84 / 116 | 60 / 100 |
| serious Total, serious adverse events | 21 / 116 | 23 / 100 |
Outcome results
Primary
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.
Time frame: Month 12 (AURORA 2 baseline) to Month 36
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Voclosporin | Adverse Events (AE) Profile and Routine Biochemical and Hematological Assessments. | Treatment-related TEAE leading to death | 0 Participants |
| Voclosporin | Adverse Events (AE) Profile and Routine Biochemical and Hematological Assessments. | Serious TEAE | 21 Participants |
| Voclosporin | Adverse Events (AE) Profile and Routine Biochemical and Hematological Assessments. | Any treatment-emergent adverse event (TEAE) | 100 Participants |
| Voclosporin | Adverse Events (AE) Profile and Routine Biochemical and Hematological Assessments. | TEAE leading to study drug discontinuation | 11 Participants |
| Voclosporin | Adverse Events (AE) Profile and Routine Biochemical and Hematological Assessments. | Disease-related TEAE | 50 Participants |
| Voclosporin | Adverse Events (AE) Profile and Routine Biochemical and Hematological Assessments. | TEAE leading to death | 0 Participants |
| Voclosporin | Adverse Events (AE) Profile and Routine Biochemical and Hematological Assessments. | Disease-related serious TEAE | 7 Participants |
| Voclosporin | Adverse Events (AE) Profile and Routine Biochemical and Hematological Assessments. | Treatment-related TEAE | 28 Participants |
| Placebo Oral Capsule | Adverse Events (AE) Profile and Routine Biochemical and Hematological Assessments. | Disease-related TEAE | 34 Participants |
| Placebo Oral Capsule | Adverse Events (AE) Profile and Routine Biochemical and Hematological Assessments. | Treatment-related TEAE | 21 Participants |
| Placebo Oral Capsule | Adverse Events (AE) Profile and Routine Biochemical and Hematological Assessments. | Serious TEAE | 23 Participants |
| Placebo Oral Capsule | Adverse Events (AE) Profile and Routine Biochemical and Hematological Assessments. | Treatment-related TEAE leading to death | 0 Participants |
| Placebo Oral Capsule | Adverse Events (AE) Profile and Routine Biochemical and Hematological Assessments. | Disease-related serious TEAE | 11 Participants |
| Placebo Oral Capsule | Adverse Events (AE) Profile and Routine Biochemical and Hematological Assessments. | Any treatment-emergent adverse event (TEAE) | 80 Participants |
| Placebo Oral Capsule | Adverse Events (AE) Profile and Routine Biochemical and Hematological Assessments. | TEAE leading to study drug discontinuation | 17 Participants |
| Placebo Oral Capsule | Adverse Events (AE) Profile and Routine Biochemical and Hematological Assessments. | TEAE leading to death | 3 Participants |
Secondary
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.
Time frame: Months 12 (AURORA 2 baseline), 18, 24, 30 and 36
Population: The number of subjects analyzed may not be aligned with overall number analyzed due to early withdrawals from study and missed study visits
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Voclosporin | Change From AURORA 1 Baseline (i.e., Month 0) in Estimated Glomerular Filtration Rate (eGFR) | Month 36 | -0.2 mL/min/1.73 m^2 | Standard Error 1.69 |
| Voclosporin | Change From AURORA 1 Baseline (i.e., Month 0) in Estimated Glomerular Filtration Rate (eGFR) | Month 12 (AURORA 2 baseline) | 1.8 mL/min/1.73 m^2 | Standard Error 1.08 |
| Voclosporin | Change From AURORA 1 Baseline (i.e., Month 0) in Estimated Glomerular Filtration Rate (eGFR) | Month 18 | -0.2 mL/min/1.73 m^2 | Standard Error 1.31 |
| Voclosporin | Change From AURORA 1 Baseline (i.e., Month 0) in Estimated Glomerular Filtration Rate (eGFR) | Month 24 | -1.3 mL/min/1.73 m^2 | Standard Error 1.48 |
| Voclosporin | Change From AURORA 1 Baseline (i.e., Month 0) in Estimated Glomerular Filtration Rate (eGFR) | Month 30 | 0.2 mL/min/1.73 m^2 | Standard Error 1.56 |
| Placebo Oral Capsule | Change From AURORA 1 Baseline (i.e., Month 0) in Estimated Glomerular Filtration Rate (eGFR) | Month 30 | -0.8 mL/min/1.73 m^2 | Standard Error 1.67 |
| Placebo Oral Capsule | Change From AURORA 1 Baseline (i.e., Month 0) in Estimated Glomerular Filtration Rate (eGFR) | Month 24 | 0.9 mL/min/1.73 m^2 | Standard Error 1.6 |
| Placebo Oral Capsule | Change From AURORA 1 Baseline (i.e., Month 0) in Estimated Glomerular Filtration Rate (eGFR) | Month 12 (AURORA 2 baseline) | 4.4 mL/min/1.73 m^2 | Standard Error 1.15 |
| Placebo Oral Capsule | Change From AURORA 1 Baseline (i.e., Month 0) in Estimated Glomerular Filtration Rate (eGFR) | Month 36 | -2.0 mL/min/1.73 m^2 | Standard Error 1.81 |
| Placebo Oral Capsule | Change From AURORA 1 Baseline (i.e., Month 0) in Estimated Glomerular Filtration Rate (eGFR) | Month 18 | 1.6 mL/min/1.73 m^2 | Standard Error 1.4 |
Comparison: Month 12 (AURORA 2 baseline)p-value: 0.04195% CI: [-5.3, -0.1]Mixed Models Analysis
Comparison: Month 18p-value: 0.29295% CI: [-5.1, 1.6]Mixed Models Analysis
Comparison: Month 24p-value: 0.28295% CI: [-6.1, 1.8]Mixed Models Analysis
Comparison: Month 30p-value: 0.65995% CI: [-3.2, 5.1]Mixed Models Analysis
Comparison: Month 36p-value: 0.43895% CI: [-2.8, 6.4]Mixed Models Analysis
Secondary
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.
Time frame: Months 18, 24 and 36
Population: The number of subjects analyzed may not be aligned with overall number analyzed due to subjects withdrawing from study and missed study visits
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Voclosporin | 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) | Month 18 | -6.4 Scores on a scale |
| Voclosporin | 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) | Month 24 | -6.8 Scores on a scale |
| Voclosporin | 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) | Month 36 | -6.8 Scores on a scale |
| Placebo Oral Capsule | 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) | Month 18 | -5.6 Scores on a scale |
| Placebo Oral Capsule | 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) | Month 24 | -6.1 Scores on a scale |
| Placebo Oral Capsule | 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) | Month 36 | -6.1 Scores on a scale |
Comparison: Month 18p-value: 0.23895% CI: [-2.1, 0.5]Mixed Models Analysis
Comparison: Month 24p-value: 0.21595% CI: [-1.8, 0.4]Mixed Models Analysis
Comparison: Month 36p-value: 0.24695% CI: [-1.8, 0.5]Mixed Models Analysis
Secondary
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.
Time frame: Months 12 (AURORA 2 baseline), 18, 24, 30 and 36
Population: The number of subjects analyzed may not be aligned with overall number analyzed due to early withdrawals from study and missed study visits
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Voclosporin | Change From AURORA 1 Baseline (i.e., Month 0) in Serum Creatinine (SCr) | Month 12 (AURORA 2 baseline) | 0.051 mg/dL | Standard Error 0.0207 |
| Voclosporin | Change From AURORA 1 Baseline (i.e., Month 0) in Serum Creatinine (SCr) | Month 30 | 0.094 mg/dL | Standard Error 0.0494 |
| Voclosporin | Change From AURORA 1 Baseline (i.e., Month 0) in Serum Creatinine (SCr) | Month 18 | 0.078 mg/dL | Standard Error 0.03 |
| Voclosporin | Change From AURORA 1 Baseline (i.e., Month 0) in Serum Creatinine (SCr) | Month 36 | 0.119 mg/dL | Standard Error 0.0597 |
| Voclosporin | Change From AURORA 1 Baseline (i.e., Month 0) in Serum Creatinine (SCr) | Month 24 | 0.117 mg/dL | Standard Error 0.0429 |
| Placebo Oral Capsule | Change From AURORA 1 Baseline (i.e., Month 0) in Serum Creatinine (SCr) | Month 36 | 0.197 mg/dL | Standard Error 0.0644 |
| Placebo Oral Capsule | Change From AURORA 1 Baseline (i.e., Month 0) in Serum Creatinine (SCr) | Month 12 (AURORA 2 baseline) | -0.034 mg/dL | Standard Error 0.0221 |
| Placebo Oral Capsule | Change From AURORA 1 Baseline (i.e., Month 0) in Serum Creatinine (SCr) | Month 24 | 0.060 mg/dL | Standard Error 0.0466 |
| Placebo Oral Capsule | Change From AURORA 1 Baseline (i.e., Month 0) in Serum Creatinine (SCr) | Month 30 | 0.129 mg/dL | Standard Error 0.0534 |
| Placebo Oral Capsule | Change From AURORA 1 Baseline (i.e., Month 0) in Serum Creatinine (SCr) | Month 18 | 0.027 mg/dL | Standard Error 0.0323 |
Comparison: Month 12 (AURORA 2 baseline)p-value: <0.00195% CI: [0.035, 0.134]Mixed Models Analysis
Comparison: Month 18p-value: 0.20995% CI: [-0.029, 0.131]Mixed Models Analysis
Comparison: Month 24p-value: 0.35395% CI: [-0.064, 0.178]Mixed Models Analysis
Comparison: Month 30p-value: 0.61695% CI: [-0.176, 0.105]Mixed Models Analysis
Comparison: Month 36p-value: 0.37295% CI: [-0.248, 0.094]Mixed Models Analysis
Secondary
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.
Time frame: Months 12 (AURORA 2 baseline), 18, 24, 30 and 36
Population: The number of subjects analyzed may not be aligned with overall number analyzed due to early withdrawals from study and missed study visits
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Voclosporin | Change From AURORA 1 Baseline (i.e., Month 0) in Urine Protein | Month 18 | -297.8 mg/dL | Standard Error 23.41 |
| Voclosporin | Change From AURORA 1 Baseline (i.e., Month 0) in Urine Protein | Month 30 | -304.7 mg/dL | Standard Error 19.23 |
| Voclosporin | Change From AURORA 1 Baseline (i.e., Month 0) in Urine Protein | Month 24 | -295.8 mg/dL | Standard Error 17.1 |
| Voclosporin | Change From AURORA 1 Baseline (i.e., Month 0) in Urine Protein | Month 36 | -280.7 mg/dL | Standard Error 22.66 |
| Voclosporin | Change From AURORA 1 Baseline (i.e., Month 0) in Urine Protein | Month 12 (AURORA 2 baseline) | -302.4 mg/dL | Standard Error 16.91 |
| Placebo Oral Capsule | Change From AURORA 1 Baseline (i.e., Month 0) in Urine Protein | Month 36 | -261.7 mg/dL | Standard Error 24.01 |
| Placebo Oral Capsule | Change From AURORA 1 Baseline (i.e., Month 0) in Urine Protein | Month 12 (AURORA 2 baseline) | -234.6 mg/dL | Standard Error 18.05 |
| Placebo Oral Capsule | Change From AURORA 1 Baseline (i.e., Month 0) in Urine Protein | Month 18 | -210.1 mg/dL | Standard Error 25.15 |
| Placebo Oral Capsule | Change From AURORA 1 Baseline (i.e., Month 0) in Urine Protein | Month 24 | -248.8 mg/dL | Standard Error 18.51 |
| Placebo Oral Capsule | Change From AURORA 1 Baseline (i.e., Month 0) in Urine Protein | Month 30 | -231.6 mg/dL | Standard Error 20.67 |
Comparison: Month 12 (AURORA 2 baseline)p-value: 0.00295% CI: [-110.4, -25.1]Mixed Models Analysis
Comparison: Month 18p-value: 0.00795% CI: [-151.2, -24.2]Mixed Models Analysis
Comparison: Month 24p-value: 0.03595% CI: [-90.8, -3.3]Mixed Models Analysis
Comparison: Month 30p-value: 0.00595% CI: [-123.5, -22.6]Mixed Models Analysis
Comparison: Month 36p-value: 0.53795% CI: [-79.7, 41.7]Mixed Models Analysis
Secondary
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.
Time frame: Months 12 (AURORA 2 baseline), 18, 24, 30 and 36
Population: The number of subjects analyzed may not be aligned with overall number analyzed due to early withdrawals from study and missed study visits
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Voclosporin | Change From AURORA 1 Baseline (i.e., Month 0) in Urine Protein to Creatinine Ratio (UPCR) | Month 18 | -3.05 mg/mg | Standard Error 0.216 |
| Voclosporin | Change From AURORA 1 Baseline (i.e., Month 0) in Urine Protein to Creatinine Ratio (UPCR) | Month 30 | -3.12 mg/mg | Standard Error 0.219 |
| Voclosporin | Change From AURORA 1 Baseline (i.e., Month 0) in Urine Protein to Creatinine Ratio (UPCR) | Month 24 | -3.18 mg/mg | Standard Error 0.188 |
| Voclosporin | Change From AURORA 1 Baseline (i.e., Month 0) in Urine Protein to Creatinine Ratio (UPCR) | Month 36 | -3.00 mg/mg | Standard Error 0.222 |
| Voclosporin | Change From AURORA 1 Baseline (i.e., Month 0) in Urine Protein to Creatinine Ratio (UPCR) | Month 12 (AURORA 2 baseline) | -3.17 mg/mg | Standard Error 0.164 |
| Placebo Oral Capsule | Change From AURORA 1 Baseline (i.e., Month 0) in Urine Protein to Creatinine Ratio (UPCR) | Month 36 | -2.52 mg/mg | Standard Error 0.236 |
| Placebo Oral Capsule | Change From AURORA 1 Baseline (i.e., Month 0) in Urine Protein to Creatinine Ratio (UPCR) | Month 12 (AURORA 2 baseline) | -2.52 mg/mg | Standard Error 0.175 |
| Placebo Oral Capsule | Change From AURORA 1 Baseline (i.e., Month 0) in Urine Protein to Creatinine Ratio (UPCR) | Month 18 | -2.42 mg/mg | Standard Error 0.232 |
| Placebo Oral Capsule | Change From AURORA 1 Baseline (i.e., Month 0) in Urine Protein to Creatinine Ratio (UPCR) | Month 24 | -2.41 mg/mg | Standard Error 0.202 |
| Placebo Oral Capsule | Change From AURORA 1 Baseline (i.e., Month 0) in Urine Protein to Creatinine Ratio (UPCR) | Month 30 | -2.21 mg/mg | Standard Error 0.235 |
Comparison: Month 12 (AURORA 2 baseline)p-value: 0.00195% CI: [-1.05, -0.26]Mixed Models Analysis
Comparison: Month 18p-value: 0.02995% CI: [-1.2, -0.07]Mixed Models Analysis
Comparison: Month 24p-value: 0.00295% CI: [-1.24, -0.29]Mixed Models Analysis
Comparison: Month 30p-value: 0.00295% CI: [-1.49, -0.33]Mixed Models Analysis
Comparison: Month 36p-value: 0.10695% CI: [-1.06, -0.1]Mixed Models Analysis
Secondary
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).
Time frame: Months 12 (AURORA 2 baseline), 18, 24, 30 and 36
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Voclosporin | Number (and Percent) of Subjects in Partial Renal Response | Partial Renal Response - Month 18 | 96 Participants |
| Voclosporin | Number (and Percent) of Subjects in Partial Renal Response | Partial Renal Response - Month 30 | 85 Participants |
| Voclosporin | Number (and Percent) of Subjects in Partial Renal Response | Partial Renal Response - Month 24 | 90 Participants |
| Voclosporin | Number (and Percent) of Subjects in Partial Renal Response | Partial Renal Response - Month 36 | 86 Participants |
| Voclosporin | Number (and Percent) of Subjects in Partial Renal Response | Partial Renal Response - Month 12 | 104 Participants |
| Placebo Oral Capsule | Number (and Percent) of Subjects in Partial Renal Response | Partial Renal Response - Month 36 | 69 Participants |
| Placebo Oral Capsule | Number (and Percent) of Subjects in Partial Renal Response | Partial Renal Response - Month 12 | 70 Participants |
| Placebo Oral Capsule | Number (and Percent) of Subjects in Partial Renal Response | Partial Renal Response - Month 18 | 68 Participants |
| Placebo Oral Capsule | Number (and Percent) of Subjects in Partial Renal Response | Partial Renal Response - Month 24 | 58 Participants |
| Placebo Oral Capsule | Number (and Percent) of Subjects in Partial Renal Response | Partial Renal Response - Month 30 | 61 Participants |
Comparison: Month 12 (AURORA 2 baseline)p-value: <0.00195% CI: [1.88, 8.46]Regression, Logistic
Comparison: Month 18p-value: 0.00895% CI: [1.28, 4.88]Regression, Logistic
Comparison: Month 24p-value: 0.00195% CI: [1.46, 4.91]Regression, Logistic
Comparison: Month 30p-value: 0.0495% CI: [1.03, 3.34]Regression, Logistic
Comparison: Month 36p-value: 0.2995% CI: [0.75, 2.58]Regression, Logistic
Secondary
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.
Time frame: Months 12 (AURORA 2 Baseline), 18, 24, 30 and 36
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Voclosporin | Number (and Percent) of Subjects in Renal Response | Renal Response - Month 18 | 74 Participants |
| Voclosporin | Number (and Percent) of Subjects in Renal Response | Renal Response - Month 30 | 69 Participants |
| Voclosporin | Number (and Percent) of Subjects in Renal Response | Renal Response - Month 24 | 65 Participants |
| Voclosporin | Number (and Percent) of Subjects in Renal Response | Renal Response - Month 36 | 59 Participants |
| Voclosporin | Number (and Percent) of Subjects in Renal Response | Renal Response - Month 12 | 61 Participants |
| Placebo Oral Capsule | Number (and Percent) of Subjects in Renal Response | Renal Response - Month 36 | 39 Participants |
| Placebo Oral Capsule | Number (and Percent) of Subjects in Renal Response | Renal Response - Month 12 | 34 Participants |
| Placebo Oral Capsule | Number (and Percent) of Subjects in Renal Response | Renal Response - Month 18 | 46 Participants |
| Placebo Oral Capsule | Number (and Percent) of Subjects in Renal Response | Renal Response - Month 24 | 43 Participants |
| Placebo Oral Capsule | Number (and Percent) of Subjects in Renal Response | Renal Response - Month 30 | 42 Participants |
Comparison: Month 12 (AURORA 2 baseline)p-value: 0.00495% CI: [1.3, 4.05]Regression, Logistic
Comparison: Month 18p-value: 0.00695% CI: [1.25, 3.83]Regression, Logistic
Comparison: Month 24p-value: 0.03595% CI: [1.04, 3.16]Regression, Logistic
Comparison: Month 30p-value: 0.00595% CI: [1.28, 3.92]Regression, Logistic
Comparison: Month 36p-value: 0.05195% CI: [1, 3.03]Regression, Logistic
Secondary
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
Time frame: Month 12 (AURORA 2 baseline) to Month 36
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Voclosporin | Renal Flare as Adjudicated by the Clinical Endpoints Committee (CEC). | Subjects without adequate response or with flares | 39 Participants |
| Voclosporin | Renal Flare as Adjudicated by the Clinical Endpoints Committee (CEC). | Subjects with adequate response and wothout flares | 77 Participants |
| Placebo Oral Capsule | Renal Flare as Adjudicated by the Clinical Endpoints Committee (CEC). | Subjects without adequate response or with flares | 46 Participants |
| Placebo Oral Capsule | Renal Flare as Adjudicated by the Clinical Endpoints Committee (CEC). | Subjects with adequate response and wothout flares | 54 Participants |
Comparison: Number of subjects with adequate renal response. This model is based on a logistic regression with terms for treatment, baseline urine protein creatinine ratio (UPCR), biopsy class, mycophenolate mofetil (MMF) use at baseline and region. An odds ratio \< unity indicates benefit for voclosporin.p-value: 0.04595% CI: [0.32, 0.99]Regression, Logistic