Lupus Nephritis
Conditions
Keywords
lupus nephritis, calcineurin inhibitors, voclosporin
Brief summary
To assess the efficacy of 2 doses of voclosporin compared to placebo in achieving complete remission after 24 weeks of therapy in subjects with active lupus nephritis.
Detailed description
Voclosporin is a next generation CNI intended for use in the prevention of organ graft rejection and for the treatment of autoimmune diseases. The aim of the current study is to investigate whether voclosporin added to the standard of care treatment in active LN is able to reduce disease activity, as measured by a reduction in proteinuria. Two doses of voclosporin will be studied and compared in a placebo controlled trial on a background of MMF and corticosteroids. Patients with active, flaring LN will be eligible to enter the study. They are required to have a diagnosis of LN according to established diagnostic criteria (American College of Rheumatology) and clinical and biopsy features suggestive of active nephritis. Efficacy will be assessed by the ability of the drug combination to reduce the level of proteinuria while demonstrating an acceptable safety profile.
Interventions
DRUGVoclosporin High Dose
DRUGVoclosporin Low Dose
DRUGPlacebo
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
Male or female subjects aged 18 to 75 years. Diagnosis of systemic lupus erythematosus (SLE) according to the American College of Rheumatology criteria. Kidney biopsy within 6 months prior to Screening (Visit 1) with a histologic diagnosis of lupus nephritis (International Society of Nephrology/Renal Pathology Society 2003 classification of lupus nephritis) Classes III, IV-S or IV-G, (A) or (A/C); or Class V, alone or in combination with Class III or IV. Laboratory evidence of active nephritis at screening, defined as: * Class III, IV-S or IV-G: Confirmed proteinuria ≥1,500 mg/24 hours when assessed by 24 hour urine collection, defined by a UPCR of ≥1.5 mg/mg assessed in a first morning void urine specimen (2 samples). * Class V (alone or in combination with Class III or IV): Confirmed proteinuria ≥2,000 mg/24 hours when assessed by 24 hour urine collection, defined by a UPCR of ≥2 mg/mg assessed in a first morning void urine specimen (2 samples).
Exclusion criteria
Estimated glomerular filtration rate (eGFR) as calculated by the Chronic Kidney Disease Epidemiology Collaboration equation of ≤45 mL/min/1.73 m2. Currently requiring renal dialysis (hemodialysis or peritoneal dialysis) or expected to require dialysis during the study period. A previous kidney transplant or planned transplant within study treatment period. In the opinion of the Investigator, subject does not require long-term immunosuppressive treatment (in addition to corticosteroids). Current or medical history of: * Pancreatitis or gastrointestinal hemorrhage within 6 months prior to screening. * Active unhealed peptic ulcer within 3 months prior to screening. If an ulcer has healed and the subject is on adequate therapy, the subject may be randomized. * Congenital or acquired immunodeficiency. * Clinically significant drug or alcohol abuse 2 years prior to screening. * Malignancy within 5 years of screening, with the exception of basal and squamous cell carcinomas treated by complete excision. Subjects with cervical dysplasia that is cervical intraepithelial neoplasia 1, but have been treated with conization or loop electrosurgical excision procedure, and have had a normal repeat PAP are allowed. * Lymphoproliferative disease or previous total lymphoid irradiation. * Severe viral infection (such as CMV, HBV, HCV) within 3 months of screening; or known human immunodeficiency virus infection. * Active tuberculosis (TB), or known history of TB/evidence of old TB if not taking prophylaxis with isoniazid. Other known clinically significant active medical conditions, such as: * Severe cardiovascular disease including congestive heart failure, history of cardiac dysrhythmia or congenital long QT syndrome. * Liver dysfunction (aspartate aminotransferase, alanine aminotransferase, or bilirubin greater than 2.5 times the upper limit of normal) at screening and confirmed before randomization. * Chronic obstructive pulmonary disease or asthma requiring oral steroids. * Bone marrow insufficiency unrelated to active SLE (according to Investigator judgment) with white blood cell count \<2,500/mm3; absolute neutrophil count \<1.3 x 103/μL; thrombocytopenia (platelet count \<50,000/mm3). * Active bleeding disorders. * Current infection requiring IV antibiotics. Any overlapping autoimmune condition for which the condition or the treatment of the condition may affect the study assessments or outcomes. Overlapping conditions for which the condition or treatment is not expected to affect assessments or outcomes are not excluded. Subjects who are pregnant, breast feeding or, if of childbearing potential, not using adequate contraceptive precautions.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects Achieving Complete Renal Remission at 24 Weeks | week 24 | Complete remission is defined as: * Confirmed protein/creatinine ratio of ≤0.5 mg/mg and * eGFR ≥60 mL/min/1.73m2 or no confirmed decrease from baseline in eGFR of ≥20%. Subjects who received rescue medication for lupus nephritis or \>10 mg prednisone for \>3 consecutive days or \>7 days total from 56 days prior to remission assessment until the time of the remission assessment were considered not achieving complete remission. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects Achieving Complete Renal Remission at 24 and 48 Weeks in the Presence of Low Dose Steroids | Weeks 24 and 48 | Complete remission is defined as: * Confirmed protein/creatinine ratio of ≤0.5 mg/mg and * eGFR ≥60 mL/min/1.73m2 or no confirmed decrease from baseline in eGFR of ≥20%. Subjects who received rescue medication for lupus nephritis or \>10 mg prednisone for \>3 consecutive days or \>7 days total from 56 days prior to remission assessment until the time of the remission assessment were considered not achieving complete remission. Low-dose steroids is defined as use of ≤5 mg prednisone for 8 weeks leading up to the Week 24 visit date or for 12 weeks leading up to the Week 48 visit date. |
| Time to Complete Remission (Number of Weeks) | week 48 | Time to Complete Remission is defined as time from first dose of voclosporin/placebo to UPCR ≤ 0.5mg in the absence of rescue medication. |
| Time to Sustained Early Complete Remission (Number of Weeks) | week 48 | Time to Sustained Complete Remission is defined as time from first dose of voclosporin/placebo to UPCR ≤ 0.5mg occurring at week 24 or earlier and sustained until week 48 in the absence of rescue medication. |
| Number of Subjects Achieving Sustained Early Complete Remission | week 48 | Sustained early complete remission defined as complete remission that occurred on or before Week 24 and was sustained through Week 48 |
| Time to Partial Remission (Number of Weeks) | week 48 | Time to partial Remission is defined as time from first dose of voclosporin/placebo to 50% UPCR reduction sustained until week 48 in the absence of rescue medication. |
| Number of Subjects Achieving Partial Remission | week 48 | Partial remission is defined as a 50% reduction in UPCR from baseline at Week 24 and Week 48. |
| Number of Subjects Achieving, and Remaining in, Complete Remission | week 48 | Sustained complete remission defined as the first occurrence of complete remission that was sustained through Week 48 |
| Number of Subjects Achieving Complete Renal Remission at 48 Weeks | Week 48 | Complete remission is defined as: * Confirmed protein/creatinine ratio of ≤0.5 mg/mg and * eGFR ≥60 mL/min/1.73m2 or no confirmed decrease from baseline in eGFR of ≥20%. Subjects who received rescue medication for lupus nephritis or \>10 mg prednisone for \>3 consecutive days or \>7 days total from 56 days prior to remission assessment until the time of the remission assessment were considered not achieving complete remission. |
| Number of Subjects Achieving Partial Renal Remission at 24 and 48 Weeks | week 24 and 48 | Number of patients with partial Remission is defined as time from first dose of voclosporin/placebo to 50% UPCR reduction at week 24 or week 48 in the absence of rescue medication. |
| Time to Sustained Partial Remission (Number of Weeks) | week 48 | Time to sustained partial Remission is defined as time from first dose of voclosporin/placebo to 50% UPCR reduction sustained until week 48 in the absence of rescue medication. |
| Number of Subjects Achieving Sustained Partial Remission | week 48 | Sustained partial remission defined as the first occurrence of partial remission that was sustained through Week 48 |
| Time to Sustained Early Partial Remission (Number of Weeks) | week 48 | Time to sustained early partial Remission is defined as time from first dose of voclosporin/placebo to 50% UPCR reduction occurring at week 24 or earlier and sustained until week 48 in the absence of rescue medication. |
| Number of Subjects Achieving Sustained Early Partial Remission | week 48 | Early partial remission defined as partial remission that occurred on or before Week 24 and was sustained through Week 48 |
| Change From Baseline in UPCR at Weeks 24 and 48 | Baseline, Week 24 and Week 48 | Change from baseline in urine protein creatinine ratio at weeks 24 and 48 |
| Change From Baseline in Safety of Estrogens in Systemic Lupus Erythematosus National Assessment Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) Score | Baseline, Week 24 and Week 48 | The SELENA-SLEDAI assesses disease activity within the last 10 days. Twenty-four items are scored for nine organ systems, and summed to a maximum of 105 points. A score of 6 is considered clinically significant and indicates active disease. For analysis purposes, a score ≥6 was categorized as high. The 24 items are as follows: seizure, psychosis, organic brain syndrome, visual disturbance, cranial nerve disorder, lupus headache, cerebrovascular accident, vasculitis, arthritis, myositis, urinary casts, hematuria, proteinuria, pyuria, new rash, alopecia, mucosal ulcers, pleurisy, pericarditis, low complement, increased DNA binding, fever, thrombocytopenia, and leukopenia. |
| Duration of Complete Remission (Number of Weeks) | week 48 | Duration of Complete Remission is defined as time of first occurrence of UPCR ≤ 0.5 mg/mg until the second increase above 0.5 mg/mg (i.e. a single occurrence above 0.5 is permitted) or use of rescue medication. |
Countries
Bangladesh, Belarus, Bulgaria, China, Ecuador, Georgia, Guatemala, Mexico, Philippines, Poland, Russia, Serbia, Singapore, South Korea, Spain, Sri Lanka, Taiwan, Thailand, Ukraine, United States
Participant flow
Pre-assignment details
Eligible subjects were randomized in a ratio of 1:1:1 to receive either voclosporin 23.7 mg BID or 39.5 mg BID, or matching placebo for 48 weeks. All subjects were also to receive 2 g/day MMF. In addition, all subjects were to receive 0.5 g/day IV methylprednisolone on Days 1 and 2 before changing to a reducing course of oral corticosteroid therapy on Day 3.
Participants by arm
| Arm | Count |
|---|---|
| Voclosporin Low Dose Voclosporin oral 23.7 mg (3 capsules) BID | 89 |
| Voclosporin High Dose Voclosporin oral 23.7 mg BID until week 2 followed by 39.5 mg (5 capsules) BID | 88 |
| Placebo Placebo capsules matched to high dose or low dose voclosporin regimen. | 88 |
| Total | 265 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 0 |
| Overall Study | Death | 10 | 2 | 1 |
| Overall Study | Lack of Efficacy | 0 | 0 | 2 |
| Overall Study | Lost to Follow-up | 1 | 1 | 3 |
| Overall Study | Physician Decision | 1 | 2 | 5 |
| Overall Study | Protocol Violation | 0 | 0 | 1 |
| Overall Study | refused to follow-up | 1 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 3 | 2 | 5 |
Baseline characteristics
| Characteristic | Total | Voclosporin High Dose | Placebo | Voclosporin Low Dose |
|---|---|---|---|---|
| Age, Continuous | 31.7 years STANDARD_DEVIATION 10.53 | 30.6 years STANDARD_DEVIATION 9.59 | 33.1 years STANDARD_DEVIATION 10.03 | 31.4 years STANDARD_DEVIATION 11.78 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 35 Participants | 13 Participants | 13 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 230 Participants | 75 Participants | 75 Participants | 80 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Lupus Nephritis history Years since diagnosis of LN (years) | 3.7 years STANDARD_DEVIATION 4.54 | 3.2 years STANDARD_DEVIATION 4.36 | 3.5 years STANDARD_DEVIATION 4.03 | 4.2 years STANDARD_DEVIATION 5.14 |
| Lupus Nephritis history Years since first significant proteinuria (years) | 3.8 years STANDARD_DEVIATION 4.66 | 3.3 years STANDARD_DEVIATION 4.22 | 3.6 years STANDARD_DEVIATION 4.06 | 4.5 years STANDARD_DEVIATION 5.53 |
| Lupus Nephritis history - Baseline eGFR | 99.8 mL/min/1.73 m2 STANDARD_DEVIATION 27.71 | 104 mL/min/1.73 m2 STANDARD_DEVIATION 27.3 | 100.2 mL/min/1.73 m2 STANDARD_DEVIATION 27.05 | 95.3 mL/min/1.73 m2 STANDARD_DEVIATION 28.4 |
| Lupus Nephritis history - Baseline UPCR | 4.69 mg/mg STANDARD_DEVIATION 3.6 | 4.48 mg/mg STANDARD_DEVIATION 3.03 | 4.43 mg/mg STANDARD_DEVIATION 3.58 | 5.16 mg/mg STANDARD_DEVIATION 4.15 |
| Race (NIH/OMB) American Indian or Alaska Native | 9 Participants | 2 Participants | 3 Participants | 4 Participants |
| Race (NIH/OMB) Asian | 132 Participants | 44 Participants | 36 Participants | 52 Participants |
| Race (NIH/OMB) Black or African American | 14 Participants | 6 Participants | 5 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) White | 108 Participants | 36 Participants | 42 Participants | 30 Participants |
| Region of Enrollment Bangladesh | 46 participants | 16 participants | 13 participants | 17 participants |
| Region of Enrollment Belarus | 13 participants | 8 participants | 4 participants | 1 participants |
| Region of Enrollment Bulgaria | 5 participants | 1 participants | 2 participants | 2 participants |
| Region of Enrollment Ecuador | 5 participants | 1 participants | 2 participants | 2 participants |
| Region of Enrollment Georgia | 5 participants | 1 participants | 3 participants | 1 participants |
| Region of Enrollment Guatemala | 11 participants | 6 participants | 3 participants | 2 participants |
| Region of Enrollment Hong Kong | 1 participants | 0 participants | 1 participants | 0 participants |
| Region of Enrollment Mexico | 14 participants | 3 participants | 8 participants | 3 participants |
| Region of Enrollment Philippines | 43 participants | 13 participants | 10 participants | 20 participants |
| Region of Enrollment Poland | 4 participants | 0 participants | 2 participants | 2 participants |
| Region of Enrollment Russia | 32 participants | 9 participants | 13 participants | 10 participants |
| Region of Enrollment Serbia | 12 participants | 1 participants | 7 participants | 4 participants |
| Region of Enrollment Singapore | 1 participants | 1 participants | 0 participants | 0 participants |
| Region of Enrollment South Korea | 7 participants | 2 participants | 2 participants | 3 participants |
| Region of Enrollment Spain | 1 participants | 0 participants | 0 participants | 1 participants |
| Region of Enrollment Sri Lanka | 14 participants | 4 participants | 5 participants | 5 participants |
| Region of Enrollment Taiwan | 5 participants | 1 participants | 2 participants | 2 participants |
| Region of Enrollment Thailand | 13 participants | 6 participants | 2 participants | 5 participants |
| Region of Enrollment Ukraine | 12 participants | 5 participants | 3 participants | 4 participants |
| Region of Enrollment United States | 21 participants | 10 participants | 6 participants | 5 participants |
| Sex: Female, Male Female | 230 Participants | 81 Participants | 73 Participants | 76 Participants |
| Sex: Female, Male Male | 35 Participants | 7 Participants | 15 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 10 / 89 | 2 / 88 | 1 / 88 |
| other Total, other adverse events | 82 / 89 | 85 / 88 | 75 / 88 |
| serious Total, serious adverse events | 25 / 89 | 22 / 88 | 14 / 88 |
Outcome results
Primary
Number of Subjects Achieving Complete Renal Remission at 24 Weeks
Complete remission is defined as: * Confirmed protein/creatinine ratio of ≤0.5 mg/mg and * eGFR ≥60 mL/min/1.73m2 or no confirmed decrease from baseline in eGFR of ≥20%. Subjects who received rescue medication for lupus nephritis or \>10 mg prednisone for \>3 consecutive days or \>7 days total from 56 days prior to remission assessment until the time of the remission assessment were considered not achieving complete remission.
Time frame: week 24
Population: Intent to Treat
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Voclosporin Low Dose | Number of Subjects Achieving Complete Renal Remission at 24 Weeks | Achieved response | 29 Participants |
| Voclosporin Low Dose | Number of Subjects Achieving Complete Renal Remission at 24 Weeks | Did not achieve response | 60 Participants |
| Voclosporin High Dose | Number of Subjects Achieving Complete Renal Remission at 24 Weeks | Achieved response | 24 Participants |
| Voclosporin High Dose | Number of Subjects Achieving Complete Renal Remission at 24 Weeks | Did not achieve response | 64 Participants |
| Placebo | Number of Subjects Achieving Complete Renal Remission at 24 Weeks | Achieved response | 17 Participants |
| Placebo | Number of Subjects Achieving Complete Renal Remission at 24 Weeks | Did not achieve response | 71 Participants |
Comparison: Voclosporin low dose vs. placebop-value: 0.04595% CI: [1.01, 4.05]Regression, Logistic
Comparison: Voclosporin high dose vs. placebop-value: 0.20495% CI: [0.78, 3.27]Regression, Logistic
Secondary
Change From Baseline in Safety of Estrogens in Systemic Lupus Erythematosus National Assessment Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) Score
The SELENA-SLEDAI assesses disease activity within the last 10 days. Twenty-four items are scored for nine organ systems, and summed to a maximum of 105 points. A score of 6 is considered clinically significant and indicates active disease. For analysis purposes, a score ≥6 was categorized as high. The 24 items are as follows: seizure, psychosis, organic brain syndrome, visual disturbance, cranial nerve disorder, lupus headache, cerebrovascular accident, vasculitis, arthritis, myositis, urinary casts, hematuria, proteinuria, pyuria, new rash, alopecia, mucosal ulcers, pleurisy, pericarditis, low complement, increased DNA binding, fever, thrombocytopenia, and leukopenia.
Time frame: Baseline, Week 24 and Week 48
Population: Intent to Treat
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Voclosporin Low Dose | Change From Baseline in Safety of Estrogens in Systemic Lupus Erythematosus National Assessment Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) Score | SELENA-SLEDAI Score Change from baseline at week 48 | -7.9 score on a scale | Standard Deviation 6.39 |
| Voclosporin Low Dose | Change From Baseline in Safety of Estrogens in Systemic Lupus Erythematosus National Assessment Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) Score | SELENA-SLEDAI Score at week 24 | 6.2 score on a scale | Standard Deviation 4.53 |
| Voclosporin Low Dose | Change From Baseline in Safety of Estrogens in Systemic Lupus Erythematosus National Assessment Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) Score | SELENA-SLEDAI Score at baseline | 12.7 score on a scale | Standard Deviation 6.37 |
| Voclosporin Low Dose | Change From Baseline in Safety of Estrogens in Systemic Lupus Erythematosus National Assessment Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) Score | SELENA-SLEDAI Score change from baseline at week 24 | -6.3 score on a scale | Standard Deviation 5.86 |
| Voclosporin Low Dose | Change From Baseline in Safety of Estrogens in Systemic Lupus Erythematosus National Assessment Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) Score | SELENA-SLEDAI Score at week 48 | 4.7 score on a scale | Standard Deviation 5.06 |
| Voclosporin High Dose | Change From Baseline in Safety of Estrogens in Systemic Lupus Erythematosus National Assessment Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) Score | SELENA-SLEDAI Score change from baseline at week 24 | -7.1 score on a scale | Standard Deviation 7.41 |
| Voclosporin High Dose | Change From Baseline in Safety of Estrogens in Systemic Lupus Erythematosus National Assessment Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) Score | SELENA-SLEDAI Score at week 48 | 5.3 score on a scale | Standard Deviation 3.97 |
| Voclosporin High Dose | Change From Baseline in Safety of Estrogens in Systemic Lupus Erythematosus National Assessment Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) Score | SELENA-SLEDAI Score at baseline | 13.9 score on a scale | Standard Deviation 6.51 |
| Voclosporin High Dose | Change From Baseline in Safety of Estrogens in Systemic Lupus Erythematosus National Assessment Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) Score | SELENA-SLEDAI Score at week 24 | 6.5 score on a scale | Standard Deviation 5.42 |
| Voclosporin High Dose | Change From Baseline in Safety of Estrogens in Systemic Lupus Erythematosus National Assessment Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) Score | SELENA-SLEDAI Score Change from baseline at week 48 | -8.3 score on a scale | Standard Deviation 6.93 |
| Placebo | Change From Baseline in Safety of Estrogens in Systemic Lupus Erythematosus National Assessment Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) Score | SELENA-SLEDAI Score Change from baseline at week 48 | -5.3 score on a scale | Standard Deviation 6.85 |
| Placebo | Change From Baseline in Safety of Estrogens in Systemic Lupus Erythematosus National Assessment Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) Score | SELENA-SLEDAI Score change from baseline at week 24 | -4.5 score on a scale | Standard Deviation 7.09 |
| Placebo | Change From Baseline in Safety of Estrogens in Systemic Lupus Erythematosus National Assessment Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) Score | SELENA-SLEDAI Score at baseline | 12.9 score on a scale | Standard Deviation 6.57 |
| Placebo | Change From Baseline in Safety of Estrogens in Systemic Lupus Erythematosus National Assessment Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) Score | SELENA-SLEDAI Score at week 24 | 8.8 score on a scale | Standard Deviation 5.43 |
| Placebo | Change From Baseline in Safety of Estrogens in Systemic Lupus Erythematosus National Assessment Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) Score | SELENA-SLEDAI Score at week 48 | 7.8 score on a scale | Standard Deviation 5.93 |
Secondary
Change From Baseline in UPCR at Weeks 24 and 48
Change from baseline in urine protein creatinine ratio at weeks 24 and 48
Time frame: Baseline, Week 24 and Week 48
Population: Intent to Treat
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Voclosporin Low Dose | Change From Baseline in UPCR at Weeks 24 and 48 | Baseline UPCR | 5.161 mg/mg | Standard Deviation 4.151 |
| Voclosporin Low Dose | Change From Baseline in UPCR at Weeks 24 and 48 | CFB at week 48 | -3.998 mg/mg | Standard Deviation 3.4208 |
| Voclosporin Low Dose | Change From Baseline in UPCR at Weeks 24 and 48 | week 24 UPCR | 1.021 mg/mg | Standard Deviation 1.2369 |
| Voclosporin Low Dose | Change From Baseline in UPCR at Weeks 24 and 48 | week 48 UPCR | 0.689 mg/mg | Standard Deviation 0.9172 |
| Voclosporin Low Dose | Change From Baseline in UPCR at Weeks 24 and 48 | CFB at week 24 | -3.769 mg/mg | Standard Deviation 3.351 |
| Voclosporin High Dose | Change From Baseline in UPCR at Weeks 24 and 48 | week 48 UPCR | 1.101 mg/mg | Standard Deviation 1.3835 |
| Voclosporin High Dose | Change From Baseline in UPCR at Weeks 24 and 48 | CFB at week 48 | -2.993 mg/mg | Standard Deviation 2.6608 |
| Voclosporin High Dose | Change From Baseline in UPCR at Weeks 24 and 48 | Baseline UPCR | 4.476 mg/mg | Standard Deviation 3.029 |
| Voclosporin High Dose | Change From Baseline in UPCR at Weeks 24 and 48 | week 24 UPCR | 1.356 mg/mg | Standard Deviation 1.5204 |
| Voclosporin High Dose | Change From Baseline in UPCR at Weeks 24 and 48 | CFB at week 24 | -2.792 mg/mg | Standard Deviation 2.6207 |
| Placebo | Change From Baseline in UPCR at Weeks 24 and 48 | week 24 UPCR | 2.266 mg/mg | Standard Deviation 2.8534 |
| Placebo | Change From Baseline in UPCR at Weeks 24 and 48 | CFB at week 48 | -2.384 mg/mg | Standard Deviation 3.454 |
| Placebo | Change From Baseline in UPCR at Weeks 24 and 48 | week 48 UPCR | 1.763 mg/mg | Standard Deviation 1.9927 |
| Placebo | Change From Baseline in UPCR at Weeks 24 and 48 | Baseline UPCR | 4.433 mg/mg | Standard Deviation 3.58 |
| Placebo | Change From Baseline in UPCR at Weeks 24 and 48 | CFB at week 24 | -2.216 mg/mg | Standard Deviation 3.9284 |
Secondary
Duration of Complete Remission (Number of Weeks)
Duration of Complete Remission is defined as time of first occurrence of UPCR ≤ 0.5 mg/mg until the second increase above 0.5 mg/mg (i.e. a single occurrence above 0.5 is permitted) or use of rescue medication.
Time frame: week 48
Population: Intent to Treat
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Voclosporin Low Dose | Duration of Complete Remission (Number of Weeks) | 49 weeks |
| Voclosporin High Dose | Duration of Complete Remission (Number of Weeks) | 25 weeks |
| Placebo | Duration of Complete Remission (Number of Weeks) | NA weeks |
Secondary
Number of Subjects Achieving, and Remaining in, Complete Remission
Sustained complete remission defined as the first occurrence of complete remission that was sustained through Week 48
Time frame: week 48
Population: Intent to Treat
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Voclosporin Low Dose | Number of Subjects Achieving, and Remaining in, Complete Remission | Number of Participants Achieving Complete Remission | 57 Participants |
| Voclosporin Low Dose | Number of Subjects Achieving, and Remaining in, Complete Remission | Number of Participants Remaining in Complete Remission | 19 Participants |
| Voclosporin Low Dose | Number of Subjects Achieving, and Remaining in, Complete Remission | Number of Participants with Second Increase of UPCR >0.5 mg/mg | 38 Participants |
| Voclosporin High Dose | Number of Subjects Achieving, and Remaining in, Complete Remission | Number of Participants Remaining in Complete Remission | 28 Participants |
| Voclosporin High Dose | Number of Subjects Achieving, and Remaining in, Complete Remission | Number of Participants Achieving Complete Remission | 61 Participants |
| Voclosporin High Dose | Number of Subjects Achieving, and Remaining in, Complete Remission | Number of Participants with Second Increase of UPCR >0.5 mg/mg | 33 Participants |
| Placebo | Number of Subjects Achieving, and Remaining in, Complete Remission | Number of Participants Remaining in Complete Remission | 10 Participants |
| Placebo | Number of Subjects Achieving, and Remaining in, Complete Remission | Number of Participants with Second Increase of UPCR >0.5 mg/mg | 22 Participants |
| Placebo | Number of Subjects Achieving, and Remaining in, Complete Remission | Number of Participants Achieving Complete Remission | 32 Participants |
Comparison: Voclosporin low dose vs. placebop-value: 0.9895% CI: [0.45, 2.15]Regression, Cox
Comparison: Voclosporin high dose vs. placebop-value: 0.11895% CI: [0.95, 4.16]Regression, Cox
Secondary
Number of Subjects Achieving Complete Renal Remission at 24 and 48 Weeks in the Presence of Low Dose Steroids
Complete remission is defined as: * Confirmed protein/creatinine ratio of ≤0.5 mg/mg and * eGFR ≥60 mL/min/1.73m2 or no confirmed decrease from baseline in eGFR of ≥20%. Subjects who received rescue medication for lupus nephritis or \>10 mg prednisone for \>3 consecutive days or \>7 days total from 56 days prior to remission assessment until the time of the remission assessment were considered not achieving complete remission. Low-dose steroids is defined as use of ≤5 mg prednisone for 8 weeks leading up to the Week 24 visit date or for 12 weeks leading up to the Week 48 visit date.
Time frame: Weeks 24 and 48
Population: Intent to Treat
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Voclosporin Low Dose | Number of Subjects Achieving Complete Renal Remission at 24 and 48 Weeks in the Presence of Low Dose Steroids | Achieved response at week 48 | 29 Participants |
| Voclosporin Low Dose | Number of Subjects Achieving Complete Renal Remission at 24 and 48 Weeks in the Presence of Low Dose Steroids | Achieved response at week 24 | 26 Participants |
| Voclosporin High Dose | Number of Subjects Achieving Complete Renal Remission at 24 and 48 Weeks in the Presence of Low Dose Steroids | Achieved response at week 48 | 26 Participants |
| Voclosporin High Dose | Number of Subjects Achieving Complete Renal Remission at 24 and 48 Weeks in the Presence of Low Dose Steroids | Achieved response at week 24 | 23 Participants |
| Placebo | Number of Subjects Achieving Complete Renal Remission at 24 and 48 Weeks in the Presence of Low Dose Steroids | Achieved response at week 24 | 17 Participants |
| Placebo | Number of Subjects Achieving Complete Renal Remission at 24 and 48 Weeks in the Presence of Low Dose Steroids | Achieved response at week 48 | 18 Participants |
p-value: 0.06695% CI: [0.96, 3.78]Regression, Logistic
p-value: 0.16295% CI: [0.82, 3.28]Regression, Logistic
Secondary
Number of Subjects Achieving Complete Renal Remission at 48 Weeks
Complete remission is defined as: * Confirmed protein/creatinine ratio of ≤0.5 mg/mg and * eGFR ≥60 mL/min/1.73m2 or no confirmed decrease from baseline in eGFR of ≥20%. Subjects who received rescue medication for lupus nephritis or \>10 mg prednisone for \>3 consecutive days or \>7 days total from 56 days prior to remission assessment until the time of the remission assessment were considered not achieving complete remission.
Time frame: Week 48
Population: Intent to Treat
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Voclosporin Low Dose | Number of Subjects Achieving Complete Renal Remission at 48 Weeks | Did not achieve response | 45 Participants |
| Voclosporin Low Dose | Number of Subjects Achieving Complete Renal Remission at 48 Weeks | Achieved response | 44 Participants |
| Voclosporin High Dose | Number of Subjects Achieving Complete Renal Remission at 48 Weeks | Achieved response | 35 Participants |
| Voclosporin High Dose | Number of Subjects Achieving Complete Renal Remission at 48 Weeks | Did not achieve response | 53 Participants |
| Placebo | Number of Subjects Achieving Complete Renal Remission at 48 Weeks | Achieved response | 21 Participants |
| Placebo | Number of Subjects Achieving Complete Renal Remission at 48 Weeks | Did not achieve response | 67 Participants |
Comparison: Voclosporin low dose vs. placebop-value: <0.00195% CI: [1.68, 6.13]Regression, Logistic
Comparison: Voclosporin high dose vs. placebop-value: 0.02695% CI: [1.09, 4.02]Regression, Logistic
Secondary
Number of Subjects Achieving Partial Remission
Partial remission is defined as a 50% reduction in UPCR from baseline at Week 24 and Week 48.
Time frame: week 48
Population: Intent to Treat
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Voclosporin Low Dose | Number of Subjects Achieving Partial Remission | 76 Participants |
| Voclosporin High Dose | Number of Subjects Achieving Partial Remission | 82 Participants |
| Placebo | Number of Subjects Achieving Partial Remission | 67 Participants |
Secondary
Number of Subjects Achieving Partial Renal Remission at 24 and 48 Weeks
Number of patients with partial Remission is defined as time from first dose of voclosporin/placebo to 50% UPCR reduction at week 24 or week 48 in the absence of rescue medication.
Time frame: week 24 and 48
Population: Intent to Treat
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Voclosporin Low Dose | Number of Subjects Achieving Partial Renal Remission at 24 and 48 Weeks | Achieved partial remission at week 24 | 62 Participants |
| Voclosporin Low Dose | Number of Subjects Achieving Partial Renal Remission at 24 and 48 Weeks | Achieved partial remission at week 48 | 61 Participants |
| Voclosporin High Dose | Number of Subjects Achieving Partial Renal Remission at 24 and 48 Weeks | Achieved partial remission at week 48 | 63 Participants |
| Voclosporin High Dose | Number of Subjects Achieving Partial Renal Remission at 24 and 48 Weeks | Achieved partial remission at week 24 | 58 Participants |
| Placebo | Number of Subjects Achieving Partial Renal Remission at 24 and 48 Weeks | Achieved partial remission at week 48 | 42 Participants |
| Placebo | Number of Subjects Achieving Partial Renal Remission at 24 and 48 Weeks | Achieved partial remission at week 24 | 43 Participants |
Comparison: week 24p-value: 0.00795% CI: [1.26, 4.33]Regression, Logistic
Comparison: week 24p-value: 0.02495% CI: [1.1, 3.76]Regression, Logistic
Comparison: week 48p-value: 0.00795% CI: [1.27, 4.33]Regression, Logistic
Comparison: week 48p-value: 0.00295% CI: [1.43, 5.02]Regression, Logistic
Secondary
Number of Subjects Achieving Sustained Early Complete Remission
Sustained early complete remission defined as complete remission that occurred on or before Week 24 and was sustained through Week 48
Time frame: week 48
Population: Intent to Treat
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Voclosporin Low Dose | Number of Subjects Achieving Sustained Early Complete Remission | 36 Participants |
| Voclosporin High Dose | Number of Subjects Achieving Sustained Early Complete Remission | 22 Participants |
| Placebo | Number of Subjects Achieving Sustained Early Complete Remission | 15 Participants |
Secondary
Number of Subjects Achieving Sustained Early Partial Remission
Early partial remission defined as partial remission that occurred on or before Week 24 and was sustained through Week 48
Time frame: week 48
Population: Intent to Treat
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Voclosporin Low Dose | Number of Subjects Achieving Sustained Early Partial Remission | 60 Participants |
| Voclosporin High Dose | Number of Subjects Achieving Sustained Early Partial Remission | 58 Participants |
| Placebo | Number of Subjects Achieving Sustained Early Partial Remission | 36 Participants |
Secondary
Number of Subjects Achieving Sustained Partial Remission
Sustained partial remission defined as the first occurrence of partial remission that was sustained through Week 48
Time frame: week 48
Population: Intent to Treat
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Voclosporin Low Dose | Number of Subjects Achieving Sustained Partial Remission | 61 Participants |
| Voclosporin High Dose | Number of Subjects Achieving Sustained Partial Remission | 63 Participants |
| Placebo | Number of Subjects Achieving Sustained Partial Remission | 42 Participants |
Secondary
Time to Complete Remission (Number of Weeks)
Time to Complete Remission is defined as time from first dose of voclosporin/placebo to UPCR ≤ 0.5mg in the absence of rescue medication.
Time frame: week 48
Population: Intent to Treat
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Voclosporin Low Dose | Time to Complete Remission (Number of Weeks) | 19.7 weeks |
| Voclosporin High Dose | Time to Complete Remission (Number of Weeks) | 23.4 weeks |
| Placebo | Time to Complete Remission (Number of Weeks) | NA weeks |
Comparison: Voclosporin low dose vs. placebop-value: <0.00195% CI: [1.45, 3.51]Regression, Cox
Comparison: Voclosporin high dose vs. placebop-value: <0.00195% CI: [1.46, 3.47]Regression, Cox
Secondary
Time to Partial Remission (Number of Weeks)
Time to partial Remission is defined as time from first dose of voclosporin/placebo to 50% UPCR reduction sustained until week 48 in the absence of rescue medication.
Time frame: week 48
Population: Intent to Treat
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Voclosporin Low Dose | Time to Partial Remission (Number of Weeks) | 4.3 weeks |
| Voclosporin High Dose | Time to Partial Remission (Number of Weeks) | 4.4 weeks |
| Placebo | Time to Partial Remission (Number of Weeks) | 6.6 weeks |
p-value: 0.00595% CI: [1.16, 2.27]Regression, Cox
Comparison: Voclosporin high dose vs. placebop-value: 0.00295% CI: [1.25, 2.43]Regression, Cox
Secondary
Time to Sustained Early Complete Remission (Number of Weeks)
Time to Sustained Complete Remission is defined as time from first dose of voclosporin/placebo to UPCR ≤ 0.5mg occurring at week 24 or earlier and sustained until week 48 in the absence of rescue medication.
Time frame: week 48
Population: Intent to Treat
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Voclosporin Low Dose | Time to Sustained Early Complete Remission (Number of Weeks) | NA weeks |
| Voclosporin High Dose | Time to Sustained Early Complete Remission (Number of Weeks) | NA weeks |
| Placebo | Time to Sustained Early Complete Remission (Number of Weeks) | NA weeks |
p-value: <0.00195% CI: [1.58, 5.29]Regression, Cox
Comparison: Voclosporin high dose vs. placebop-value: <0.24895% CI: [0.77, 2.86]Regression, Cox
Secondary
Time to Sustained Early Partial Remission (Number of Weeks)
Time to sustained early partial Remission is defined as time from first dose of voclosporin/placebo to 50% UPCR reduction occurring at week 24 or earlier and sustained until week 48 in the absence of rescue medication.
Time frame: week 48
Population: Intent to Treat
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Voclosporin Low Dose | Time to Sustained Early Partial Remission (Number of Weeks) | 6.3 weeks |
| Voclosporin High Dose | Time to Sustained Early Partial Remission (Number of Weeks) | 8.1 weeks |
| Placebo | Time to Sustained Early Partial Remission (Number of Weeks) | NA weeks |
Comparison: Voclosporin low dose vs. placebop-value: <0.00195% CI: [1.45, 3.36]Regression, Cox
Comparison: Voclosporin high dose vs. placebop-value: 0.00495% CI: [1.23, 2.84]Regression, Cox
Secondary
Time to Sustained Partial Remission (Number of Weeks)
Time to sustained partial Remission is defined as time from first dose of voclosporin/placebo to 50% UPCR reduction sustained until week 48 in the absence of rescue medication.
Time frame: week 48
Population: Intent to Treat
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Voclosporin Low Dose | Time to Sustained Partial Remission (Number of Weeks) | 6.3 weeks |
| Voclosporin High Dose | Time to Sustained Partial Remission (Number of Weeks) | 8.1 weeks |
| Placebo | Time to Sustained Partial Remission (Number of Weeks) | 26.9 weeks |
Comparison: Voclosporin low dose vs. placebop-value: <0.00195% CI: [1.36, 3.03]Regression, Cox
Comparison: Voclosporin high dose vs. placebop-value: 0.00495% CI: [1.22, 2.69]Regression, Cox