Lupus Nephritis
Conditions
Keywords
Systemic Lupus Erythematosus (SLE), Lupus Nephritis (LN), secukinumab, renal biopsy, estimated Glomerular Filtration Rate (eGFR), Urine Protein-to-Creatinine Ratio (UPCR), Standard of Care (SoC) background therapy
Brief summary
This was a pivotal, randomized, double-blind, placebo-controlled trial evaluating at Week 52 the efficacy and safety of secukinumab versus placebo in patients with active lupus nephritis (ISN/RPS Class III or IV, with or without co-existing class V features) also receiving background standard of care therapy (SoC).
Detailed description
The study consisted of the following parts: * Screening (up to 42 days/6 weeks) * Run-in period (optional): For subjects who received Mycophenolic acid (MPA) as SoC induction therapy as per investigator's decision and who were not already on MPA at Screening, MPA dosing was initiated during a run-in period before Randomization (for up to 4 weeks prior to the first dose of secukinumab) * Treatment Period: Duration of 104 weeks of treatment with secukinumab/placebo in addition to SoC treatment (with last dose given at Week 100) * Secukinumab dosing was started with initial dosing of 300 mg s.c. injections at Baseline, Weeks 1, 2, 3, and 4, followed by dosing every 4 weeks * Follow-up period: Duration of 8 weeks (last visit performed 12 weeks after last dose of study medication) for all except for subjects entering extension study CAIN457Q12301E1 (NCT05232864). A total of 275 subjects were enrolled and were randomized to secukinumab 300 mg (n = 137) or placebo (n = 138) until study termination. Recruitment in this study was stopped on 26-May-2023. The CAIN457Q12301 study was terminated early by Novartis due to futile results from interim analysis 1 (IA1). There was no safety related reasons for early termination or concerns for the subjects in the study. The decision was made to terminate both the core and the related extension study in view of treatment futility of the core study.
Interventions
DRUGsecukinumab
STUDY DRUG
DRUGPlacebo
Placebo
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
double-blind
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
Key inclusion criteria: 1. Adult male and female subjects aged 18 - 75 years old at the time of Baseline. 2. Confirmed diagnosis of: * SLE with documented history of at least 4 of the 11 criteria for SLE as defined by the American College of Rheumatology (ACR) (Tan et al 1982) revised by (Hochberg 1997). \[NOTE: The 4 criteria did not have to be present at the time of Screening\], OR * LN as the sole clinical criterion in the presence of ANA or anti-dsDNA antibodies. 3. Active lupus nephritis, as defined by meeting the 4 following criteria: * Biopsy within 6 months prior to Screening visit indicating active glomerulonephritis WHO or ISN/RPS Class III or IV LN \[excluding III (C), IV-S (C) and IV-G (C)\]; patients are permitted to have co-existing Class V. If no biopsy was performed within 6 months of screening, a biopsy was to be performed during the Screening period * UPCR ≥ 1 mg/mg at Screening. * eGFR \> 30 mL/min/1.73 m2 by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI). * Active urinary sediment (presence of cellular casts (RBC or WBC casts)) or hematuria (\> 5 RBC per high power field or above the laboratory reference range). 4. Subjects must have currently been on MPA, or willing to initiate SoC induction therapy for LN according to the institutional practices using MPA or low-dose CYC in addition to corticosteroids. For guidance, see published guidelines such as by (Bertsias et al 2012, Hahn et al 2012). 5. Subjects must had been treated with anti-malarials (e.g. hydroxychloroquine), unless contra-indicated, and the dose had been stable for at least 10 days prior to Randomization. 6. Able to provide signed informed consent. Key
Exclusion criteria
1. Severe renal impairment as defined by i.) Stage 4 CKD, or ii.) presence of oliguria (defined as a documented urine volume \< 400 mL/24 h), or iii.) ESRD required dialysis or transplantation. 2. Known intolerance/hypersensitivity to MPA, or oral corticosteroids, or any component of the study drug(s). 3. Subjects received any other biologic immunomodulatory therapy within 6 months prior to Screening, excluding belimumab where 3 months were acceptable. 4. Previous exposure to secukinumab (AIN457) or any other biologic drug targeting IL-17 or the IL-17 receptor. 5. Subjects received any investigational drug within 1 month or five times the half-life of enrollment, whichever was longer. 6. Receipt of more than 3000 mg i.v. pulse methylprednisolone (cumulative dose) within the 12 weeks prior to Baseline. 7. Treatment with a systemic calcineurin inhibitor (e.g. cyclosporine, tacrolimus) within 12 weeks prior to Baseline 8. CYC use (i.v. or oral) within the month prior to Baseline. 9. Subjects requiring dialysis within the previous 12 months before Screening. 10. History of renal transplant. 11. Any severe progressive or uncontrolled concurrent medical condition, including recent severe thromboembolic events, that, in the opinion of the principal investigator, renders the subject unsuitable for the trial. 12. Active ongoing inflammatory diseases that might confound the evaluation of the benefit of secukinumab therapy, including inflammatory bowel disease. 13. Presence of investigator-identified significant medical problems which at the investigator's discretion would prevent the subject from participating in the study, included but not limited to the following: myocarditis, pericarditis, poorly controlled seizure disorder, acute confusional state, depression, severe manifestations of neuropsychiatric SLE (NPSLE). 14. Chest X-ray, computerized tomography (CT) scan, or MRI with evidence of ongoing infectious or malignant process, obtained within 3 months preceding the Screening visit and evaluated by a qualified physician. 15. History of chronic, recurrent systemic infections, active tuberculosis infection, or active systemic infections during the last two weeks (exception: common cold) prior to Randomization. 16. Known infection with human immunodeficiency virus (HIV), hepatitis B or hepatitis C at Screening or Randomization. 17. History of lymphoproliferative disease or any known malignancy or history of malignancy of any organ system treated or untreated within the past 5 years, regardless of whether there was evidence of local recurrence or metastases (except for skin Bowen's disease or basal cell carcinoma or actinic keratoses that had been treated with no evidence of recurrence in the past 12 weeks, carcinoma in situ of the cervix or non-invasive malignant colon polyps that had been removed). 18. Any of the following abnormal laboratory values on Screening evaluations as reported by Central Laboratory: * Aspartate aminotransferase (AST), alanine aminotransferase (ALT), or amylase \> 2.5xULN * Hemoglobin \< 8g/dL * Neutrophils \< 1.0 x 109/L * Platelet count \< 50 x 109/L 21\. Pregnant or lactating women. 22. Women of childbearing potential, defined as all women physiologically capable of becoming pregnant, unless they were using highly effective methods of contraception during the entire study or longer if required by locally approved prescribing information (e.g., in European Union (EU) 20 weeks). Of note: the highly effective methods of contraception were mandated due to SoC medications used as per protocol (MPA and CYC). In case local regulations deviated from the contraception methods listed above, local regulations applied and were described in the informed consent form (ICF). If stricter female or male contraception requirements were specified in the country-specific label for induction and maintenance standard of care medications, they had to be followed. Note: Women were considered post-menopausal and not of childbearing potential if they had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g., age appropriate, history of vasomotor symptoms) or had surgical bilateral oophorectomy (with or without hysterectomy), total hysterectomy or tubal ligation at least six weeks prior to enrollment. In the case of oophorectomy alone, only when the reproductive status of the woman had been confirmed by follow-up hormone level assessment was she considered not of childbearing potential.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving Complete Renal Response (CRR) at Week 52 | Baseline, Week 52 | Complete Renal Response (CRR) is a composite endpoint defined as: * Estimated Glomerular Filtration Rate (eGFR) \>= 60 mL/min/1.73 m\^2 or no less than 85% of core Baseline values and * 24-hour Urine-to-Protein Creatinine Ratio (UPCR) =\< 0.5mg/mg * No treatment discontinuation before Week 52 * The subject did not receive more than 10 mg/day prednisone or equivalent for \>= 3 consecutive days or for \>= 7 days in total during Week 44 through Week 52. Non-responder imputation (NRI) was used for participants who did not have the required data to compute responses at Week 52 or who had discontinued study treatment before Week 52. A logistic regression model was used for the analysis of this endpoint. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving Partial Renal Response (PRR) at Week 52 | Baseline, Week 52 | Partial Renal Response (PRR) is a composite endpoint defined as: * \>= 50% reduction in 24-hour Urine-to-Protein Creatinine Ratio (UPCR) to sub-nephrotic levels (=\< 3 mg/mg) and * Estimated Glomerular Filtration Rate (eGFR) \>= 60 mL/min/1.73 m\^2 or no less than 85% of Baseline |
| Average Daily Dose of Oral Corticosteroids | Week 16 to Week 52 | Average daily dose of oral corticosteroids doses was used to assess efficacy of secukinumab compared to placebo in the averaged daily dose of oral corticosteroids administered between Week 16 and Week 52. |
| Percentage of Participants Achieving Partial Renal Response (PRR) at Week 24 | Baseline, Week 24 | Partial Renal Response (PRR) is a composite endpoint defined as: * \>= 50% reduction in 24-hour Urine-to-Protein Creatinine Ratio (UPCR) to sub-nephrotic levels (=\< 3 mg/mg) and * Estimated Glomerular Filtration Rate (eGFR) \>= 60 mL/min/1.73 m\^2 or no less than 85% of Baseline |
| Incidence Rate of Participants Achieving Complete Renal Response (CRR) up to Week 52 | Baseline to Week 52 | Time to achieve Complete Renal Response (CRR) up to week 52 was evaluated by 4-week interval by using Kaplan-Meier estimates. Participants who did not achieve CRR were censored at the date of their last non-missing CRR result (including participants who completed week 52 without achieving CRR). * Subjects at risk = Subjects who did not achieve CRR and were not censored before or at the start of the specified interval. Participants had an event when achieving CRR. * Incidence rate (%) = (number of subjects with event/number of subjects at risk) x 100. |
| Incidence Rate of Participants Achieving Partial Renal Response (PRR) up to Week 52 | Baseline to Week 52 | Time to achieve Partial Renal Response (PRR) up to week 52 was evaluated by 4-week interval by using Kaplan-Meier estimates. Participants who did not achieve PRR were censored at the date of their last non-missing PRR result (including participants who completed week 52 without achieving PRR). Participants had event when achieving PRR. * Subjects at risk = Subjects who did not achieve PRR and were not censored before or at the start of the specified interval. * Incidence rate (%) = (number of subjects with event/ number of subjects at risk) x 100. |
| Time to Achieve First Morning Void Urine Protein-to-Creatinine Ratio (UPCR) <= 0.5 mg/mg up to Week 52 | Baseline to Week 52 | Time to achieve first morning void Urine Protein-to-Creatinine Ratio (UPCR) \<= 0.5 mg/mg up to week 52 was evaluated by 4-week interval by using Kaplan-Meier estimates. Participants who did not achieve UCPR were censored at the date of their last non-missing UCPR result (including participants who completed week 52 without achieving UCPR). Participants had event when achieving UCPR. * Subjects at risk = Subjects who did not achieve UCPR and were not censored before or at the start of the specified interval. * Incidence rate (%) = (number of subjects with event/ number of subjects at risk) x 100. |
| Change From Baseline in 24-hour Urine Protein-to Creatinine Ratio (UPCR) | Baseline, Week 52 | Urine Protein-to-Creatinine Ratio (UPCR) was determined by a central laboratory by dividing the protein concentration by the creatinine concentration as measured in the urine collected (24-hour urine collection sample). |
| Short Form Health Survey (SF-36) Version 2 (Acute Form) Mean Change From Baseline in Physical Component Score (PCS) up to Week 52 | Baseline, Week 12, Week 24, Week 36, Week 52 | The SF-36 questionnaire consists of eight scales yielding two summary measures: physical and mental health. The physical health measure includes four scales of physical functioning (10 items), role-physical (4 items), bodily pain (2 items), and general health (5 items). The mental health measure is composed of vitality (4 items), social functioning (2 items), role-emotional (3 items), and mental health (5 items). In this trial, SF-36-PCS responder (improvement of \>= 2.5 points) were evaluated. Responses to items allow for direct calculation of scale scores, while the physical component summary (PCS) scores are computed from weighted scale scores. For all scales and summary measures, higher scores indicate better health outcomes (PCS scores range 0 to 100). |
| Lupus Quality of Life (LupusQoL) Physical Health Score Mean Change From Baseline up to Week 52 | Baseline, Week 12, Week 24, Week 36, Week 52 | The LupusQoL is a disease-specific, 34-item, self-report questionnaire designed to measure the health-related quality of life (HRQoL) of subjects with SLE within 8 domains (i.e., physical health (8 items), emotional health (6 items), body image (5 items), pain (3 items), planning (3 items), fatigue (4 items), intimate relationships (2 items), and burden to others (3 items)). Responses are based on a 5-point Likert scale where 0 (all of the time) to 4 (never). Each domain of the LupusQoL was scored separately. Transformed scores range from 0 (worst HRQoL) to 100 (best HRQoL). |
| Incidence of Adverse Events (AEs), Serious Adverse Events (SAEs) | From first dose of study treatment up to approximately 2 years | The distribution of adverse events was done via the analysis of frequencies for treatment emergent Adverse Event (TEAEs), Serious Adverse Event (TESAEs) and Deaths due to AEs, through the monitoring of relevant clinical and laboratory safety parameters. |
| Percentage of Participants With Complete Renal Response (CRR) at Week 104 Within Those Who Had Achieved CRR at Week 52 in the Secukinumab Group | Week 52 to Week 104 | The percentage of participants with maintained renal response (CRR) at Week 104 in the secukinumab group was evaluated |
| Percentage of Participants With Improved or Maintained Response (PRR or CRR) at Week 104 in Those Who Had Achieved at Least PRR at Week 52 in the Secukinumab Group | Week 52 to Week 104 | The percentage of participants with improved or maintained renal response (CRR) at Week 104 in the secukinumab group was evaluated |
| Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue) Mean Change From Baseline up to Week 52 | Baseline, Week 12, Week 24, Week 36, Week 52 | The FACIT-Fatigue is a 13-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function over the past week. The purpose of the FACIT-Fatigue in this study was to assess the impact of fatigue on subjects with lupus nephritis (LN). The level of fatigue was measured on a 5-point Likert scale (0 = not at all, 1 = a little bit, 2 = somewhat, 3 = quite a bit, 4 = very much) based on their experience of fatigue during the past 2 weeks. The scale score is computed by summing the item scores, after reversing those items that are worded in the negative direction. FACIT-Fatigue scale score range from 0 to 52, where higher scores represent less fatigue. |
Countries
Argentina, Australia, Brazil, Canada, Chile, China, Colombia, Croatia, Czechia, Denmark, France, Germany, Greece, Guatemala, India, Italy, Japan, Mexico, Norway, Peru, Philippines, Portugal, Romania, Russia, Slovakia, South Korea, Spain, Sweden, Switzerland, Taiwan, Thailand, Turkey (Türkiye), United States, Vietnam
Participant flow
Recruitment details
This study was conducted in 106 centers in 34 countries worldwide.
Pre-assignment details
At Baseline, all eligible subjects were randomized in a 1:1 ratio to secukinumab 300 mg s.c. or placebo via Interactive Response Technology (IRT).
Participants by arm
| Arm | Count |
|---|---|
| Secukinumab 300 mg A blinded, weekly, subcutaneous (s.c.) secukinumab 300 mg loading regimen was administered for the first 4 weeks followed by a monthly maintenance dose in all randomized subjects thereafter (maximum treatment exposure during the core study: 786 days). | 137 |
| Placebo A blinded, weekly, subcutaneous (s.c.) matching placebo loading regimen was administered for the first 4 weeks followed by a monthly maintenance dose in all randomized subjects thereafter (maximum treatment exposure during the core study: 794 days). | 138 |
| Total | 275 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 3 |
| Overall Study | Death | 1 | 1 |
| Overall Study | Lack of Efficacy | 2 | 2 |
| Overall Study | Lost to Follow-up | 1 | 1 |
| Overall Study | Physician Decision | 1 | 3 |
| Overall Study | Pregnancy | 0 | 1 |
| Overall Study | Protocol deviation | 1 | 0 |
| Overall Study | Study terminated by sponsor | 95 | 97 |
| Overall Study | Subject decision | 11 | 4 |
| Overall Study | Withdrawal of informed consent | 1 | 3 |
Baseline characteristics
| Characteristic | Secukinumab 300 mg | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 34.1 Years STANDARD_DEVIATION 10.84 | 33.2 Years STANDARD_DEVIATION 11.28 | 33.6 Years STANDARD_DEVIATION 11.05 |
| Age, Customized < 30 years | 55 Participants | 64 Participants | 119 Participants |
| Age, Customized >= 30 years | 82 Participants | 74 Participants | 156 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 21 Participants | 21 Participants | 42 Participants |
| Race (NIH/OMB) Asian | 67 Participants | 56 Participants | 123 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants | 9 Participants | 15 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 42 Participants | 52 Participants | 94 Participants |
| Sex: Female, Male Female | 116 Participants | 124 Participants | 240 Participants |
| Sex: Female, Male Male | 21 Participants | 14 Participants | 35 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 137 | 1 / 138 |
| other Total, other adverse events | 111 / 137 | 116 / 138 |
| serious Total, serious adverse events | 30 / 137 | 39 / 138 |
Outcome results
Primary
Percentage of Participants Achieving Complete Renal Response (CRR) at Week 52
Complete Renal Response (CRR) is a composite endpoint defined as: * Estimated Glomerular Filtration Rate (eGFR) \>= 60 mL/min/1.73 m\^2 or no less than 85% of core Baseline values and * 24-hour Urine-to-Protein Creatinine Ratio (UPCR) =\< 0.5mg/mg * No treatment discontinuation before Week 52 * The subject did not receive more than 10 mg/day prednisone or equivalent for \>= 3 consecutive days or for \>= 7 days in total during Week 44 through Week 52. Non-responder imputation (NRI) was used for participants who did not have the required data to compute responses at Week 52 or who had discontinued study treatment before Week 52. A logistic regression model was used for the analysis of this endpoint.
Time frame: Baseline, Week 52
Population: Full Analysis Set 2.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Secukinumab 300 mg | Percentage of Participants Achieving Complete Renal Response (CRR) at Week 52 | 25.9 Percentage of participants |
| Placebo | Percentage of Participants Achieving Complete Renal Response (CRR) at Week 52 | 38.6 Percentage of participants |
Comparison: Complete Renal Response (CRR) at Week 52p-value: 0.066295% CI: [-26.3, 0.9]Regression, Logistic
Secondary
Average Daily Dose of Oral Corticosteroids
Average daily dose of oral corticosteroids doses was used to assess efficacy of secukinumab compared to placebo in the averaged daily dose of oral corticosteroids administered between Week 16 and Week 52.
Time frame: Week 16 to Week 52
Population: Full Analysis Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Secukinumab 300 mg | Average Daily Dose of Oral Corticosteroids | 8.1243 mg/day | Standard Deviation 6.38329 |
| Placebo | Average Daily Dose of Oral Corticosteroids | 7.4791 mg/day | Standard Deviation 5.61958 |
Secondary
Change From Baseline in 24-hour Urine Protein-to Creatinine Ratio (UPCR)
Urine Protein-to-Creatinine Ratio (UPCR) was determined by a central laboratory by dividing the protein concentration by the creatinine concentration as measured in the urine collected (24-hour urine collection sample).
Time frame: Baseline, Week 52
Population: Full Analysis Set. Only participants with a value at both Baseline and post-baseline visit included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Secukinumab 300 mg | Change From Baseline in 24-hour Urine Protein-to Creatinine Ratio (UPCR) | -2.204 mg/mg | Standard Deviation 3.5162 |
| Placebo | Change From Baseline in 24-hour Urine Protein-to Creatinine Ratio (UPCR) | -2.741 mg/mg | Standard Deviation 5.9448 |
Secondary
Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue) Mean Change From Baseline up to Week 52
The FACIT-Fatigue is a 13-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function over the past week. The purpose of the FACIT-Fatigue in this study was to assess the impact of fatigue on subjects with lupus nephritis (LN). The level of fatigue was measured on a 5-point Likert scale (0 = not at all, 1 = a little bit, 2 = somewhat, 3 = quite a bit, 4 = very much) based on their experience of fatigue during the past 2 weeks. The scale score is computed by summing the item scores, after reversing those items that are worded in the negative direction. FACIT-Fatigue scale score range from 0 to 52, where higher scores represent less fatigue.
Time frame: Baseline, Week 12, Week 24, Week 36, Week 52
Population: Full Analysis Set. Only participants with a value at both Baseline and post-baseline visit included.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Secukinumab 300 mg | Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue) Mean Change From Baseline up to Week 52 | Week 12 | -2.8 Unit on a scale | Standard Deviation 8.47 |
| Secukinumab 300 mg | Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue) Mean Change From Baseline up to Week 52 | Week 24 | -1.4 Unit on a scale | Standard Deviation 9.66 |
| Secukinumab 300 mg | Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue) Mean Change From Baseline up to Week 52 | Week 36 | -2.6 Unit on a scale | Standard Deviation 9.21 |
| Secukinumab 300 mg | Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue) Mean Change From Baseline up to Week 52 | Week 52 | -2.0 Unit on a scale | Standard Deviation 10.18 |
| Placebo | Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue) Mean Change From Baseline up to Week 52 | Week 52 | -2.0 Unit on a scale | Standard Deviation 9.51 |
| Placebo | Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue) Mean Change From Baseline up to Week 52 | Week 12 | -1.9 Unit on a scale | Standard Deviation 8.46 |
| Placebo | Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue) Mean Change From Baseline up to Week 52 | Week 36 | -2.1 Unit on a scale | Standard Deviation 9.67 |
| Placebo | Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue) Mean Change From Baseline up to Week 52 | Week 24 | -2.0 Unit on a scale | Standard Deviation 8.93 |
Secondary
Incidence of Adverse Events (AEs), Serious Adverse Events (SAEs)
The distribution of adverse events was done via the analysis of frequencies for treatment emergent Adverse Event (TEAEs), Serious Adverse Event (TESAEs) and Deaths due to AEs, through the monitoring of relevant clinical and laboratory safety parameters.
Time frame: From first dose of study treatment up to approximately 2 years
Population: Safety Set (SAF).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Secukinumab 300 mg | Incidence of Adverse Events (AEs), Serious Adverse Events (SAEs) | Deaths | 1 Participants |
| Secukinumab 300 mg | Incidence of Adverse Events (AEs), Serious Adverse Events (SAEs) | Serious Adverse Event (TESAEs) | 30 Participants |
| Secukinumab 300 mg | Incidence of Adverse Events (AEs), Serious Adverse Events (SAEs) | Treatment Emergent Adverse Event (TEAEs) | 120 Participants |
| Secukinumab 300 mg | Incidence of Adverse Events (AEs), Serious Adverse Events (SAEs) | TESAEs leading to study medication discontinuation | 8 Participants |
| Placebo | Incidence of Adverse Events (AEs), Serious Adverse Events (SAEs) | TESAEs leading to study medication discontinuation | 10 Participants |
| Placebo | Incidence of Adverse Events (AEs), Serious Adverse Events (SAEs) | Deaths | 1 Participants |
| Placebo | Incidence of Adverse Events (AEs), Serious Adverse Events (SAEs) | Treatment Emergent Adverse Event (TEAEs) | 123 Participants |
| Placebo | Incidence of Adverse Events (AEs), Serious Adverse Events (SAEs) | Serious Adverse Event (TESAEs) | 39 Participants |
Secondary
Incidence Rate of Participants Achieving Complete Renal Response (CRR) up to Week 52
Time to achieve Complete Renal Response (CRR) up to week 52 was evaluated by 4-week interval by using Kaplan-Meier estimates. Participants who did not achieve CRR were censored at the date of their last non-missing CRR result (including participants who completed week 52 without achieving CRR). * Subjects at risk = Subjects who did not achieve CRR and were not censored before or at the start of the specified interval. Participants had an event when achieving CRR. * Incidence rate (%) = (number of subjects with event/number of subjects at risk) x 100.
Time frame: Baseline to Week 52
Population: Participants in the Full Analysis Set with an available value for the outcome measure. Day 1 = Date of randomization.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Secukinumab 300 mg | Incidence Rate of Participants Achieving Complete Renal Response (CRR) up to Week 52 | 57 to 84 days | 3.1 Percentage of participants |
| Secukinumab 300 mg | Incidence Rate of Participants Achieving Complete Renal Response (CRR) up to Week 52 | 197 to 224 days | 1.4 Percentage of participants |
| Secukinumab 300 mg | Incidence Rate of Participants Achieving Complete Renal Response (CRR) up to Week 52 | 113 to 140 days | 0.0 Percentage of participants |
| Secukinumab 300 mg | Incidence Rate of Participants Achieving Complete Renal Response (CRR) up to Week 52 | 225 to 252 days | 0.0 Percentage of participants |
| Secukinumab 300 mg | Incidence Rate of Participants Achieving Complete Renal Response (CRR) up to Week 52 | 29 to 56 days | 0.0 Percentage of participants |
| Secukinumab 300 mg | Incidence Rate of Participants Achieving Complete Renal Response (CRR) up to Week 52 | 253 to 280 days | 14.8 Percentage of participants |
| Secukinumab 300 mg | Incidence Rate of Participants Achieving Complete Renal Response (CRR) up to Week 52 | 141 to 168 days | 0.0 Percentage of participants |
| Secukinumab 300 mg | Incidence Rate of Participants Achieving Complete Renal Response (CRR) up to Week 52 | 281 to 308 days | 0.0 Percentage of participants |
| Secukinumab 300 mg | Incidence Rate of Participants Achieving Complete Renal Response (CRR) up to Week 52 | 85 to 112 days | 11.7 Percentage of participants |
| Secukinumab 300 mg | Incidence Rate of Participants Achieving Complete Renal Response (CRR) up to Week 52 | 309 to 336 days | 0.0 Percentage of participants |
| Secukinumab 300 mg | Incidence Rate of Participants Achieving Complete Renal Response (CRR) up to Week 52 | 169 to 196 days | 20.4 Percentage of participants |
| Secukinumab 300 mg | Incidence Rate of Participants Achieving Complete Renal Response (CRR) up to Week 52 | 337 to 364 days | 2.3 Percentage of participants |
| Secukinumab 300 mg | Incidence Rate of Participants Achieving Complete Renal Response (CRR) up to Week 52 | 1 to 28 days | 0.0 Percentage of participants |
| Placebo | Incidence Rate of Participants Achieving Complete Renal Response (CRR) up to Week 52 | 337 to 364 days | 7.3 Percentage of participants |
| Placebo | Incidence Rate of Participants Achieving Complete Renal Response (CRR) up to Week 52 | 1 to 28 days | 0.8 Percentage of participants |
| Placebo | Incidence Rate of Participants Achieving Complete Renal Response (CRR) up to Week 52 | 29 to 56 days | 0.0 Percentage of participants |
| Placebo | Incidence Rate of Participants Achieving Complete Renal Response (CRR) up to Week 52 | 57 to 84 days | 5.4 Percentage of participants |
| Placebo | Incidence Rate of Participants Achieving Complete Renal Response (CRR) up to Week 52 | 85 to 112 days | 16.8 Percentage of participants |
| Placebo | Incidence Rate of Participants Achieving Complete Renal Response (CRR) up to Week 52 | 113 to 140 days | 2.2 Percentage of participants |
| Placebo | Incidence Rate of Participants Achieving Complete Renal Response (CRR) up to Week 52 | 141 to 168 days | 3.4 Percentage of participants |
| Placebo | Incidence Rate of Participants Achieving Complete Renal Response (CRR) up to Week 52 | 169 to 196 days | 20.0 Percentage of participants |
| Placebo | Incidence Rate of Participants Achieving Complete Renal Response (CRR) up to Week 52 | 197 to 224 days | 0.0 Percentage of participants |
| Placebo | Incidence Rate of Participants Achieving Complete Renal Response (CRR) up to Week 52 | 225 to 252 days | 0.0 Percentage of participants |
| Placebo | Incidence Rate of Participants Achieving Complete Renal Response (CRR) up to Week 52 | 253 to 280 days | 3.6 Percentage of participants |
| Placebo | Incidence Rate of Participants Achieving Complete Renal Response (CRR) up to Week 52 | 281 to 308 days | 2.1 Percentage of participants |
| Placebo | Incidence Rate of Participants Achieving Complete Renal Response (CRR) up to Week 52 | 309 to 336 days | 0.0 Percentage of participants |
Secondary
Incidence Rate of Participants Achieving Partial Renal Response (PRR) up to Week 52
Time to achieve Partial Renal Response (PRR) up to week 52 was evaluated by 4-week interval by using Kaplan-Meier estimates. Participants who did not achieve PRR were censored at the date of their last non-missing PRR result (including participants who completed week 52 without achieving PRR). Participants had event when achieving PRR. * Subjects at risk = Subjects who did not achieve PRR and were not censored before or at the start of the specified interval. * Incidence rate (%) = (number of subjects with event/ number of subjects at risk) x 100.
Time frame: Baseline to Week 52
Population: Participants in the Full Analysis Set with an available value for the outcome measure. Day 1 = Date of randomization.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Secukinumab 300 mg | Incidence Rate of Participants Achieving Partial Renal Response (PRR) up to Week 52 | 57 to 84 days | 7.0 Percentage of participants |
| Secukinumab 300 mg | Incidence Rate of Participants Achieving Partial Renal Response (PRR) up to Week 52 | 197 to 224 days | 2.4 Percentage of participants |
| Secukinumab 300 mg | Incidence Rate of Participants Achieving Partial Renal Response (PRR) up to Week 52 | 113 to 140 days | 1.3 Percentage of participants |
| Secukinumab 300 mg | Incidence Rate of Participants Achieving Partial Renal Response (PRR) up to Week 52 | 225 to 252 days | 2.6 Percentage of participants |
| Secukinumab 300 mg | Incidence Rate of Participants Achieving Partial Renal Response (PRR) up to Week 52 | 29 to 56 days | 0.0 Percentage of participants |
| Secukinumab 300 mg | Incidence Rate of Participants Achieving Partial Renal Response (PRR) up to Week 52 | 253 to 280 days | 11.8 Percentage of participants |
| Secukinumab 300 mg | Incidence Rate of Participants Achieving Partial Renal Response (PRR) up to Week 52 | 141 to 168 days | 0.0 Percentage of participants |
| Secukinumab 300 mg | Incidence Rate of Participants Achieving Partial Renal Response (PRR) up to Week 52 | 281 to 308 days | 4.0 Percentage of participants |
| Secukinumab 300 mg | Incidence Rate of Participants Achieving Partial Renal Response (PRR) up to Week 52 | 85 to 112 days | 27.8 Percentage of participants |
| Secukinumab 300 mg | Incidence Rate of Participants Achieving Partial Renal Response (PRR) up to Week 52 | 309 to 336 days | 0.0 Percentage of participants |
| Secukinumab 300 mg | Incidence Rate of Participants Achieving Partial Renal Response (PRR) up to Week 52 | 169 to 196 days | 32.4 Percentage of participants |
| Secukinumab 300 mg | Incidence Rate of Participants Achieving Partial Renal Response (PRR) up to Week 52 | 337 to 364 days | 0.0 Percentage of participants |
| Secukinumab 300 mg | Incidence Rate of Participants Achieving Partial Renal Response (PRR) up to Week 52 | 1 to 28 days | 0.0 Percentage of participants |
| Placebo | Incidence Rate of Participants Achieving Partial Renal Response (PRR) up to Week 52 | 337 to 364 days | 6.5 Percentage of participants |
| Placebo | Incidence Rate of Participants Achieving Partial Renal Response (PRR) up to Week 52 | 1 to 28 days | 0.8 Percentage of participants |
| Placebo | Incidence Rate of Participants Achieving Partial Renal Response (PRR) up to Week 52 | 29 to 56 days | 0.0 Percentage of participants |
| Placebo | Incidence Rate of Participants Achieving Partial Renal Response (PRR) up to Week 52 | 57 to 84 days | 5.4 Percentage of participants |
| Placebo | Incidence Rate of Participants Achieving Partial Renal Response (PRR) up to Week 52 | 85 to 112 days | 30.5 Percentage of participants |
| Placebo | Incidence Rate of Participants Achieving Partial Renal Response (PRR) up to Week 52 | 113 to 140 days | 2.6 Percentage of participants |
| Placebo | Incidence Rate of Participants Achieving Partial Renal Response (PRR) up to Week 52 | 141 to 168 days | 4.1 Percentage of participants |
| Placebo | Incidence Rate of Participants Achieving Partial Renal Response (PRR) up to Week 52 | 169 to 196 days | 14.9 Percentage of participants |
| Placebo | Incidence Rate of Participants Achieving Partial Renal Response (PRR) up to Week 52 | 197 to 224 days | 0.0 Percentage of participants |
| Placebo | Incidence Rate of Participants Achieving Partial Renal Response (PRR) up to Week 52 | 225 to 252 days | 0.0 Percentage of participants |
| Placebo | Incidence Rate of Participants Achieving Partial Renal Response (PRR) up to Week 52 | 253 to 280 days | 16.3 Percentage of participants |
| Placebo | Incidence Rate of Participants Achieving Partial Renal Response (PRR) up to Week 52 | 281 to 308 days | 2.9 Percentage of participants |
| Placebo | Incidence Rate of Participants Achieving Partial Renal Response (PRR) up to Week 52 | 309 to 336 days | 0.0 Percentage of participants |
Secondary
Lupus Quality of Life (LupusQoL) Physical Health Score Mean Change From Baseline up to Week 52
The LupusQoL is a disease-specific, 34-item, self-report questionnaire designed to measure the health-related quality of life (HRQoL) of subjects with SLE within 8 domains (i.e., physical health (8 items), emotional health (6 items), body image (5 items), pain (3 items), planning (3 items), fatigue (4 items), intimate relationships (2 items), and burden to others (3 items)). Responses are based on a 5-point Likert scale where 0 (all of the time) to 4 (never). Each domain of the LupusQoL was scored separately. Transformed scores range from 0 (worst HRQoL) to 100 (best HRQoL).
Time frame: Baseline, Week 12, Week 24, Week 36, Week 52
Population: Full Analysis Set. Only participants with a value at both Baseline and post-baseline visit included.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Secukinumab 300 mg | Lupus Quality of Life (LupusQoL) Physical Health Score Mean Change From Baseline up to Week 52 | Week 12 | 5.32 Unit on a scale | Standard Deviation 16.031 |
| Secukinumab 300 mg | Lupus Quality of Life (LupusQoL) Physical Health Score Mean Change From Baseline up to Week 52 | Week 24 | 4.84 Unit on a scale | Standard Deviation 18.184 |
| Secukinumab 300 mg | Lupus Quality of Life (LupusQoL) Physical Health Score Mean Change From Baseline up to Week 52 | Week 36 | 5.59 Unit on a scale | Standard Deviation 20.684 |
| Secukinumab 300 mg | Lupus Quality of Life (LupusQoL) Physical Health Score Mean Change From Baseline up to Week 52 | Week 52 | 7.62 Unit on a scale | Standard Deviation 23.275 |
| Placebo | Lupus Quality of Life (LupusQoL) Physical Health Score Mean Change From Baseline up to Week 52 | Week 52 | 8.55 Unit on a scale | Standard Deviation 20.589 |
| Placebo | Lupus Quality of Life (LupusQoL) Physical Health Score Mean Change From Baseline up to Week 52 | Week 12 | 6.18 Unit on a scale | Standard Deviation 19.248 |
| Placebo | Lupus Quality of Life (LupusQoL) Physical Health Score Mean Change From Baseline up to Week 52 | Week 36 | 7.89 Unit on a scale | Standard Deviation 23.112 |
| Placebo | Lupus Quality of Life (LupusQoL) Physical Health Score Mean Change From Baseline up to Week 52 | Week 24 | 5.55 Unit on a scale | Standard Deviation 20.485 |
Secondary
Percentage of Participants Achieving Partial Renal Response (PRR) at Week 24
Partial Renal Response (PRR) is a composite endpoint defined as: * \>= 50% reduction in 24-hour Urine-to-Protein Creatinine Ratio (UPCR) to sub-nephrotic levels (=\< 3 mg/mg) and * Estimated Glomerular Filtration Rate (eGFR) \>= 60 mL/min/1.73 m\^2 or no less than 85% of Baseline
Time frame: Baseline, Week 24
Population: Full Analysis Set. Only participants with a value at both Baseline and post-baseline visit included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Secukinumab 300 mg | Percentage of Participants Achieving Partial Renal Response (PRR) at Week 24 | 52.8 Percentage of participants |
| Placebo | Percentage of Participants Achieving Partial Renal Response (PRR) at Week 24 | 43.6 Percentage of participants |
Secondary
Percentage of Participants Achieving Partial Renal Response (PRR) at Week 52
Partial Renal Response (PRR) is a composite endpoint defined as: * \>= 50% reduction in 24-hour Urine-to-Protein Creatinine Ratio (UPCR) to sub-nephrotic levels (=\< 3 mg/mg) and * Estimated Glomerular Filtration Rate (eGFR) \>= 60 mL/min/1.73 m\^2 or no less than 85% of Baseline
Time frame: Baseline, Week 52
Population: Full Analysis Set. Only participants with a value at both Baseline and post-baseline visit included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Secukinumab 300 mg | Percentage of Participants Achieving Partial Renal Response (PRR) at Week 52 | 56.2 Percentage of participants |
| Placebo | Percentage of Participants Achieving Partial Renal Response (PRR) at Week 52 | 63.9 Percentage of participants |
Comparison: Partial Renal Response (PRR) at Week 5295% CI: [-23.7, 8.4]
Secondary
Percentage of Participants With Complete Renal Response (CRR) at Week 104 Within Those Who Had Achieved CRR at Week 52 in the Secukinumab Group
The percentage of participants with maintained renal response (CRR) at Week 104 in the secukinumab group was evaluated
Time frame: Week 52 to Week 104
Population: Participants in the Full Analysis Set who received secukinumab. Subset of participants who achieved CRR at Week 52 and had an available CRR assessment at Week 104.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Secukinumab 300 mg | Percentage of Participants With Complete Renal Response (CRR) at Week 104 Within Those Who Had Achieved CRR at Week 52 in the Secukinumab Group | Achieve CRR | 5 Participants |
| Secukinumab 300 mg | Percentage of Participants With Complete Renal Response (CRR) at Week 104 Within Those Who Had Achieved CRR at Week 52 in the Secukinumab Group | Not Achieve CRR | 1 Participants |
Secondary
Percentage of Participants With Improved or Maintained Response (PRR or CRR) at Week 104 in Those Who Had Achieved at Least PRR at Week 52 in the Secukinumab Group
The percentage of participants with improved or maintained renal response (CRR) at Week 104 in the secukinumab group was evaluated
Time frame: Week 52 to Week 104
Population: Participants in the Full Analysis Set who received secukinumab. Subset of participants who achieved PRR or CRR at Week 52 and had an available PRR or CRR assessment at Week 104.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Secukinumab 300 mg | Percentage of Participants With Improved or Maintained Response (PRR or CRR) at Week 104 in Those Who Had Achieved at Least PRR at Week 52 in the Secukinumab Group | Achieve PRR or CRR | 11 Participants |
| Secukinumab 300 mg | Percentage of Participants With Improved or Maintained Response (PRR or CRR) at Week 104 in Those Who Had Achieved at Least PRR at Week 52 in the Secukinumab Group | Not achieve PRR or CRR | 1 Participants |
Secondary
Short Form Health Survey (SF-36) Version 2 (Acute Form) Mean Change From Baseline in Physical Component Score (PCS) up to Week 52
The SF-36 questionnaire consists of eight scales yielding two summary measures: physical and mental health. The physical health measure includes four scales of physical functioning (10 items), role-physical (4 items), bodily pain (2 items), and general health (5 items). The mental health measure is composed of vitality (4 items), social functioning (2 items), role-emotional (3 items), and mental health (5 items). In this trial, SF-36-PCS responder (improvement of \>= 2.5 points) were evaluated. Responses to items allow for direct calculation of scale scores, while the physical component summary (PCS) scores are computed from weighted scale scores. For all scales and summary measures, higher scores indicate better health outcomes (PCS scores range 0 to 100).
Time frame: Baseline, Week 12, Week 24, Week 36, Week 52
Population: Full Analysis Set. Only participants with a value at both Baseline and post-baseline visit included.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Secukinumab 300 mg | Short Form Health Survey (SF-36) Version 2 (Acute Form) Mean Change From Baseline in Physical Component Score (PCS) up to Week 52 | Week 12 | 2.306 Unit on a scale | Standard Deviation 6.4306 |
| Secukinumab 300 mg | Short Form Health Survey (SF-36) Version 2 (Acute Form) Mean Change From Baseline in Physical Component Score (PCS) up to Week 52 | Week 24 | 2.873 Unit on a scale | Standard Deviation 6.4502 |
| Secukinumab 300 mg | Short Form Health Survey (SF-36) Version 2 (Acute Form) Mean Change From Baseline in Physical Component Score (PCS) up to Week 52 | Week 36 | 2.910 Unit on a scale | Standard Deviation 6.8234 |
| Secukinumab 300 mg | Short Form Health Survey (SF-36) Version 2 (Acute Form) Mean Change From Baseline in Physical Component Score (PCS) up to Week 52 | Week 52 | 3.410 Unit on a scale | Standard Deviation 7.7123 |
| Placebo | Short Form Health Survey (SF-36) Version 2 (Acute Form) Mean Change From Baseline in Physical Component Score (PCS) up to Week 52 | Week 52 | 2.707 Unit on a scale | Standard Deviation 6.8887 |
| Placebo | Short Form Health Survey (SF-36) Version 2 (Acute Form) Mean Change From Baseline in Physical Component Score (PCS) up to Week 52 | Week 12 | 2.210 Unit on a scale | Standard Deviation 6.876 |
| Placebo | Short Form Health Survey (SF-36) Version 2 (Acute Form) Mean Change From Baseline in Physical Component Score (PCS) up to Week 52 | Week 36 | 3.152 Unit on a scale | Standard Deviation 7.0623 |
| Placebo | Short Form Health Survey (SF-36) Version 2 (Acute Form) Mean Change From Baseline in Physical Component Score (PCS) up to Week 52 | Week 24 | 1.687 Unit on a scale | Standard Deviation 6.5346 |
Secondary
Time to Achieve First Morning Void Urine Protein-to-Creatinine Ratio (UPCR) <= 0.5 mg/mg up to Week 52
Time to achieve first morning void Urine Protein-to-Creatinine Ratio (UPCR) \<= 0.5 mg/mg up to week 52 was evaluated by 4-week interval by using Kaplan-Meier estimates. Participants who did not achieve UCPR were censored at the date of their last non-missing UCPR result (including participants who completed week 52 without achieving UCPR). Participants had event when achieving UCPR. * Subjects at risk = Subjects who did not achieve UCPR and were not censored before or at the start of the specified interval. * Incidence rate (%) = (number of subjects with event/ number of subjects at risk) x 100.
Time frame: Baseline to Week 52
Population: Participants in the Full Analysis Set with an available value for the outcome measure. Day 1 = Date of randomization.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Secukinumab 300 mg | Time to Achieve First Morning Void Urine Protein-to-Creatinine Ratio (UPCR) <= 0.5 mg/mg up to Week 52 | 57 to 84 days | 8.7 Percentage of participants |
| Secukinumab 300 mg | Time to Achieve First Morning Void Urine Protein-to-Creatinine Ratio (UPCR) <= 0.5 mg/mg up to Week 52 | 197 to 224 days | 7.5 Percentage of participants |
| Secukinumab 300 mg | Time to Achieve First Morning Void Urine Protein-to-Creatinine Ratio (UPCR) <= 0.5 mg/mg up to Week 52 | 113 to 140 days | 7.6 Percentage of participants |
| Secukinumab 300 mg | Time to Achieve First Morning Void Urine Protein-to-Creatinine Ratio (UPCR) <= 0.5 mg/mg up to Week 52 | 225 to 252 days | 4.2 Percentage of participants |
| Secukinumab 300 mg | Time to Achieve First Morning Void Urine Protein-to-Creatinine Ratio (UPCR) <= 0.5 mg/mg up to Week 52 | 29 to 56 days | 2.8 Percentage of participants |
| Secukinumab 300 mg | Time to Achieve First Morning Void Urine Protein-to-Creatinine Ratio (UPCR) <= 0.5 mg/mg up to Week 52 | 253 to 280 days | 4.4 Percentage of participants |
| Secukinumab 300 mg | Time to Achieve First Morning Void Urine Protein-to-Creatinine Ratio (UPCR) <= 0.5 mg/mg up to Week 52 | 141 to 168 days | 9.9 Percentage of participants |
| Secukinumab 300 mg | Time to Achieve First Morning Void Urine Protein-to-Creatinine Ratio (UPCR) <= 0.5 mg/mg up to Week 52 | 281 to 308 days | 12.2 Percentage of participants |
| Secukinumab 300 mg | Time to Achieve First Morning Void Urine Protein-to-Creatinine Ratio (UPCR) <= 0.5 mg/mg up to Week 52 | 85 to 112 days | 11.8 Percentage of participants |
| Secukinumab 300 mg | Time to Achieve First Morning Void Urine Protein-to-Creatinine Ratio (UPCR) <= 0.5 mg/mg up to Week 52 | 309 to 336 days | 0.0 Percentage of participants |
| Secukinumab 300 mg | Time to Achieve First Morning Void Urine Protein-to-Creatinine Ratio (UPCR) <= 0.5 mg/mg up to Week 52 | 169 to 196 days | 9.7 Percentage of participants |
| Secukinumab 300 mg | Time to Achieve First Morning Void Urine Protein-to-Creatinine Ratio (UPCR) <= 0.5 mg/mg up to Week 52 | 337 to 364 days | 3.1 Percentage of participants |
| Secukinumab 300 mg | Time to Achieve First Morning Void Urine Protein-to-Creatinine Ratio (UPCR) <= 0.5 mg/mg up to Week 52 | 1 to 28 days | 19.3 Percentage of participants |
| Placebo | Time to Achieve First Morning Void Urine Protein-to-Creatinine Ratio (UPCR) <= 0.5 mg/mg up to Week 52 | 337 to 364 days | 2.9 Percentage of participants |
| Placebo | Time to Achieve First Morning Void Urine Protein-to-Creatinine Ratio (UPCR) <= 0.5 mg/mg up to Week 52 | 1 to 28 days | 21.3 Percentage of participants |
| Placebo | Time to Achieve First Morning Void Urine Protein-to-Creatinine Ratio (UPCR) <= 0.5 mg/mg up to Week 52 | 29 to 56 days | 5.6 Percentage of participants |
| Placebo | Time to Achieve First Morning Void Urine Protein-to-Creatinine Ratio (UPCR) <= 0.5 mg/mg up to Week 52 | 57 to 84 days | 7.0 Percentage of participants |
| Placebo | Time to Achieve First Morning Void Urine Protein-to-Creatinine Ratio (UPCR) <= 0.5 mg/mg up to Week 52 | 85 to 112 days | 9.7 Percentage of participants |
| Placebo | Time to Achieve First Morning Void Urine Protein-to-Creatinine Ratio (UPCR) <= 0.5 mg/mg up to Week 52 | 113 to 140 days | 7.4 Percentage of participants |
| Placebo | Time to Achieve First Morning Void Urine Protein-to-Creatinine Ratio (UPCR) <= 0.5 mg/mg up to Week 52 | 141 to 168 days | 6.9 Percentage of participants |
| Placebo | Time to Achieve First Morning Void Urine Protein-to-Creatinine Ratio (UPCR) <= 0.5 mg/mg up to Week 52 | 169 to 196 days | 3.2 Percentage of participants |
| Placebo | Time to Achieve First Morning Void Urine Protein-to-Creatinine Ratio (UPCR) <= 0.5 mg/mg up to Week 52 | 197 to 224 days | 11.9 Percentage of participants |
| Placebo | Time to Achieve First Morning Void Urine Protein-to-Creatinine Ratio (UPCR) <= 0.5 mg/mg up to Week 52 | 225 to 252 days | 6.0 Percentage of participants |
| Placebo | Time to Achieve First Morning Void Urine Protein-to-Creatinine Ratio (UPCR) <= 0.5 mg/mg up to Week 52 | 253 to 280 days | 0.0 Percentage of participants |
| Placebo | Time to Achieve First Morning Void Urine Protein-to-Creatinine Ratio (UPCR) <= 0.5 mg/mg up to Week 52 | 281 to 308 days | 4.5 Percentage of participants |
| Placebo | Time to Achieve First Morning Void Urine Protein-to-Creatinine Ratio (UPCR) <= 0.5 mg/mg up to Week 52 | 309 to 336 days | 5.1 Percentage of participants |