Lupus Nephritis
Conditions
Keywords
immunoproteasome inhibition, selective immunoproteasome inhibition, complete renal response, partial renal response, glucocorticoids, steroids, SLE (systemic lupus erythematosus), UPCR (urine protein to creatinine ratio), eGFR (estimated glomerular filtration rate)
Brief summary
The purpose of this study was to assess the efficacy and safety of zetomipzomib (30 mg or 60 mg) compared with placebo in achieving renal response after 52 weeks of treatment in patients with active lupus nephritis (LN).
Detailed description
This study aimed to investigate whether zetomipzomib, added to standard of care treatment in patients with active LN, was able to reduce disease activity over a treatment period of 52 weeks. The background standard of care therapy was mycophenolate mofetil (MMF) and initial optional treatment with IV methylprednisolone, followed by a tapering course of oral corticosteroids. Patients were required to have a diagnosis of LN according to established diagnostic criteria and clinical and biopsy features suggestive of active nephritis. Patients were randomized in a 2:1 ratio to receive either zetomipzomib (30 mg or 60 mg) or placebo administered as a subcutaneous injection once weekly for 52 weeks, followed by a 4-week safety follow-up period. Efficacy was to be assessed by measuring the level of proteinuria (as measured by urine protein to creatinine ratio \[UPCR\]) and estimated glomerular filtration rate (eGFR) as compared to current standard of care treatment. Safety was also assessed throughout the study to ensure an acceptable safety profile.
Interventions
DRUGzetomipzomib
Subcutaneous injection of zetomipzomib
DRUGplacebo
Subcutaneous injection of placebo
Sponsors
Kezar Life Sciences, 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 No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Body mass index of ≥18 kg/m\^2 * eGFR ≥30 mL/min/1.73 m\^2 * Unequivocally positive ANA test result and/or a positive anti-dsDNA serum antibody test * Diagnosis of LN according to 2003 or 2018 ISN/RPS criteria and confirmed by renal biopsy performed within 12 months prior to Screening. * UPCR ≥1.0 (Class III/IV +/-V) or UPCR ≥2.0 (Class V) * Adequate hematologic, hepatic, and renal function Key
Exclusion criteria
* Current or medical history of: * Central nervous system manifestations of SLE * Overlapping autoimmune condition that may affect study assessments/outcomes * Antiphospholipid syndrome with history of thromboembolic event of within the 52 weeks prior to Screening * Thrombocytopenia or at high risk for developing clinically significant bleeding or organ dysfunction requiring therapies (i.e., plasmapheresis or acute blood or platelet transfusions * Solid organ transplant or planned transplant during study * Malignancy of any type, with exceptions for non-melanoma skin cancers and certain cancers \>5 years ago * Has received dialysis within the 52 weeks prior to Screening * Positive test at Screening for HIV, hepatitis B/C * Known intolerance to MMF or equivalent and corticosteroids
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Patients Achieving Complete Renal Response | Week 37 | Proportion of patients achieving complete renal response (CRR), defined as: * A UPCR ≤0.5 in one 24-hour urine sample (for primary endpoint and Week 53) or 2 consecutive first morning void urine samples (for all other time points) * An eGFR ≥60 mL/min/1.73 m\^2 or no confirmed decrease of \>20% from Baseline eGFR. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Patients Achieving Complete Renal Response | Week 25 | Proportion of patients achieving complete renal response (CRR) |
| Change in UPCR | Week 13, Week 25, and Week 37 | Percentage change from Baseline in Urine Protein to Creatinine Ratio (UPCR) by visit |
| Proportion of Patients Achieving Partial Renal Response (PRR) | Week 25 and Week 37 | Proportion of patients achieving PRR, defined as a: ≥50% reduction of UPCR from Baseline, and to \<1.0 if the Baseline UPCR was \<3.0 or to \<3.0 if the Baseline value was ≥3.0. |
| Proportion of Patients With UPCR ≤0.5 | Week 13, Week 25, and Week 37 | Proportion of patients with UPCR ≤0.5 |
| Percent Change in the Systemic Lupus Erythematosus (SLE) Disease Activity Index 2000 (SLEDAI-2K) | Week 13, Week 25, and Week 37 | Percent change from Baseline in clinical SLEDAI-2K score. The SLEDAI-2K score falls between 0 and 105. A higher score represents greater disease activity. |
| Time to Complete Renal Response and Partial Renal Response | Baseline through Week 37 | The comparison of the time to Complete Renal Response and Partial Renal Response for the zetomipzomib treatment groups (zetomipzomib 30mg and zetomipzomib 60mg) versus placebo. Hazard ratio (HR) and associated two-sided CIs are estimated using the Cox proportional hazards model. The model includes terms for treatment, the randomization stratification factors, and baseline UPCR (continuous). |
Countries
Argentina, Brazil, China, Colombia, Greece, Guatemala, India, Malaysia, Philippines, South Africa, South Korea, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Zetomipzomib 30 mg + Standard-of-care Participants randomized to be treated with initial 30 mg dose of zetomipzomib, followed by weekly doses of 30 mg zetomipzomib through the treatment period in addition to background standard of care therapy. | 27 |
| Zetomipzomib 60 mg + Standard-of-care Participants randomized to be treated with initial 30 mg dose of zetomipzomib, followed by weekly doses of 60 mg zetomipzomib through the treatment period in addition to background standard of care therapy. | 29 |
| Placebo + Standard-of-care Participants randomized to be treated with initial 30 mg dose of placebo, followed by weekly doses (30 mg or 60 mg) of placebo through the treatment period in addition to background standard of care therapy. | 28 |
| Total | 84 |
Baseline characteristics
| Characteristic | Zetomipzomib 30 mg + Standard-of-care | Zetomipzomib 60 mg + Standard-of-care | Placebo + Standard-of-care | Total |
|---|---|---|---|---|
| Age, Continuous | 31.0 years STANDARD_DEVIATION 10.54 | 32.5 years STANDARD_DEVIATION 9.44 | 32.8 years STANDARD_DEVIATION 9.1 | 32.1 years STANDARD_DEVIATION 9.61 |
| Average 24-hour UPCR at Baseline | 3.7 mg/mg STANDARD_DEVIATION 2 | 3.6 mg/mg STANDARD_DEVIATION 2.1 | 3.1 mg/mg STANDARD_DEVIATION 1.6 | 3.5 mg/mg STANDARD_DEVIATION 1.9 |
| Average 24-hour UPCR at Screening ≤3.0 mg/mg | 13 Participants | 15 Participants | 13 Participants | 41 Participants |
| Average 24-hour UPCR at Screening >3.0 mg/mg | 14 Participants | 14 Participants | 15 Participants | 43 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 10 Participants | 13 Participants | 28 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 22 Participants | 19 Participants | 15 Participants | 56 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| LN Class Class III/IV ± V | 23 participants | 26 participants | 24 participants | 73 participants |
| LN Class Pure Class V | 4 participants | 3 participants | 4 participants | 11 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 5 Participants | 2 Participants | 8 Participants |
| Race (NIH/OMB) Asian | 19 Participants | 15 Participants | 13 Participants | 47 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 3 Participants | 5 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 | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) White | 6 Participants | 7 Participants | 9 Participants | 22 Participants |
| Sex: Female, Male Female | 25 Participants | 28 Participants | 25 Participants | 78 Participants |
| Sex: Female, Male Male | 2 Participants | 1 Participants | 3 Participants | 6 Participants |
| SLEDAI-2K | 11.8 score on a scale STANDARD_DEVIATION 5.28 | 11.7 score on a scale STANDARD_DEVIATION 5.48 | 10.5 score on a scale STANDARD_DEVIATION 5.02 | 11.3 score on a scale STANDARD_DEVIATION 5.23 |
| Time from LN diagnosis to Screening | 1.8 years STANDARD_DEVIATION 2.3 | 5.0 years STANDARD_DEVIATION 5.4 | 4.3 years STANDARD_DEVIATION 4.5 | 3.7 years STANDARD_DEVIATION 4.5 |
| Time from SLE diagnosis to Screening | 4.7 years STANDARD_DEVIATION 5 | 8.1 years STANDARD_DEVIATION 6.2 | 6.7 years STANDARD_DEVIATION 5.8 | 6.5 years STANDARD_DEVIATION 5.8 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 27 | 1 / 29 | 1 / 28 |
| other Total, other adverse events | 23 / 27 | 25 / 29 | 17 / 28 |
| serious Total, serious adverse events | 5 / 27 | 8 / 29 | 3 / 28 |
Outcome results
Primary
Proportion of Patients Achieving Complete Renal Response
Proportion of patients achieving complete renal response (CRR), defined as: * A UPCR ≤0.5 in one 24-hour urine sample (for primary endpoint and Week 53) or 2 consecutive first morning void urine samples (for all other time points) * An eGFR ≥60 mL/min/1.73 m\^2 or no confirmed decrease of \>20% from Baseline eGFR.
Time frame: Week 37
Population: Participants in the intent to treat analysis set who reached Week 37 of treatment. Intent-to-treat set was defined as the set of all participants who are randomized to the study. This analysis focuses on the participants with Class III/IV ± Class V lupus nephritis. Due to the early termination of the study, not all participants reached the 37 week timepoint for efficacy analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Zetomipzomib 30 mg + Standard-of-care | Proportion of Patients Achieving Complete Renal Response | 0 Participants |
| Zetomipzomib 60 mg + Standard-of-care | Proportion of Patients Achieving Complete Renal Response | 1 Participants |
| Placebo + Standard-of-care | Proportion of Patients Achieving Complete Renal Response | 0 Participants |
Secondary
Change in UPCR
Percentage change from Baseline in Urine Protein to Creatinine Ratio (UPCR) by visit
Time frame: Week 13, Week 25, and Week 37
Population: Participants in the intent to treat set, defined as the set of all participants who are randomized to the study. This analysis focuses on the participants with Class III/IV ± Class V lupus nephritis. Due to the early termination of the study, not all participants reached the timepoints for efficacy analysis and no participants completed the full 52-week treatment period.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Zetomipzomib 30 mg + Standard-of-care | Change in UPCR | Week 25 | -37.27 percent change in 24-hr UPCR value | Standard Deviation 45 |
| Zetomipzomib 30 mg + Standard-of-care | Change in UPCR | Week 13 | -33.08 percent change in 24-hr UPCR value | Standard Deviation 34.37 |
| Zetomipzomib 30 mg + Standard-of-care | Change in UPCR | Week 37 | -68.39 percent change in 24-hr UPCR value | — |
| Zetomipzomib 60 mg + Standard-of-care | Change in UPCR | Week 25 | -61.56 percent change in 24-hr UPCR value | Standard Deviation 50.85 |
| Zetomipzomib 60 mg + Standard-of-care | Change in UPCR | Week 13 | -46.33 percent change in 24-hr UPCR value | Standard Deviation 55.16 |
| Zetomipzomib 60 mg + Standard-of-care | Change in UPCR | Week 37 | -72.59 percent change in 24-hr UPCR value | Standard Deviation 29.91 |
| Placebo + Standard-of-care | Change in UPCR | Week 13 | -32.27 percent change in 24-hr UPCR value | Standard Deviation 35.24 |
| Placebo + Standard-of-care | Change in UPCR | Week 37 | -23.08 percent change in 24-hr UPCR value | Standard Deviation 17.43 |
| Placebo + Standard-of-care | Change in UPCR | Week 25 | -40.33 percent change in 24-hr UPCR value | Standard Deviation 42.47 |
Secondary
Percent Change in the Systemic Lupus Erythematosus (SLE) Disease Activity Index 2000 (SLEDAI-2K)
Percent change from Baseline in clinical SLEDAI-2K score. The SLEDAI-2K score falls between 0 and 105. A higher score represents greater disease activity.
Time frame: Week 13, Week 25, and Week 37
Population: Participants in the intent to treat set, defined as the set of all participants who are randomized to the study. This analysis focuses on the participants with Class III/IV ± Class V lupus nephritis. Due to the early termination of the study, not all participants reached the timepoints for efficacy analysis and no participants completed the full 52-week treatment period.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Zetomipzomib 30 mg + Standard-of-care | Percent Change in the Systemic Lupus Erythematosus (SLE) Disease Activity Index 2000 (SLEDAI-2K) | Week 25 | -18.6 percent change of SLEDAI-2K score | Standard Deviation 45.9 |
| Zetomipzomib 30 mg + Standard-of-care | Percent Change in the Systemic Lupus Erythematosus (SLE) Disease Activity Index 2000 (SLEDAI-2K) | Week 13 | -14.0 percent change of SLEDAI-2K score | Standard Deviation 45.4 |
| Zetomipzomib 30 mg + Standard-of-care | Percent Change in the Systemic Lupus Erythematosus (SLE) Disease Activity Index 2000 (SLEDAI-2K) | Week 37 | -28.6 percent change of SLEDAI-2K score | — |
| Zetomipzomib 60 mg + Standard-of-care | Percent Change in the Systemic Lupus Erythematosus (SLE) Disease Activity Index 2000 (SLEDAI-2K) | Week 25 | -59.2 percent change of SLEDAI-2K score | Standard Deviation 33.6 |
| Zetomipzomib 60 mg + Standard-of-care | Percent Change in the Systemic Lupus Erythematosus (SLE) Disease Activity Index 2000 (SLEDAI-2K) | Week 13 | -56.4 percent change of SLEDAI-2K score | Standard Deviation 24.1 |
| Zetomipzomib 60 mg + Standard-of-care | Percent Change in the Systemic Lupus Erythematosus (SLE) Disease Activity Index 2000 (SLEDAI-2K) | Week 37 | -36.4 percent change of SLEDAI-2K score | Standard Deviation 51.4 |
| Placebo + Standard-of-care | Percent Change in the Systemic Lupus Erythematosus (SLE) Disease Activity Index 2000 (SLEDAI-2K) | Week 13 | -19.5 percent change of SLEDAI-2K score | Standard Deviation 33.7 |
| Placebo + Standard-of-care | Percent Change in the Systemic Lupus Erythematosus (SLE) Disease Activity Index 2000 (SLEDAI-2K) | Week 37 | -5.0 percent change of SLEDAI-2K score | Standard Deviation 32.8 |
| Placebo + Standard-of-care | Percent Change in the Systemic Lupus Erythematosus (SLE) Disease Activity Index 2000 (SLEDAI-2K) | Week 25 | -27.2 percent change of SLEDAI-2K score | Standard Deviation 32.6 |
Secondary
Proportion of Patients Achieving Complete Renal Response
Proportion of patients achieving complete renal response (CRR)
Time frame: Week 25
Population: Participants in the intent to treat set, defined as the set of all participants who are randomized to the study. This analysis focuses on the participants with Class III/IV ± Class V lupus nephritis. Due to the early termination of the study, not all participants reached the timepoints for efficacy analysis and no participants completed the full 52-week treatment period.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Zetomipzomib 30 mg + Standard-of-care | Proportion of Patients Achieving Complete Renal Response | 1 Participants |
| Zetomipzomib 60 mg + Standard-of-care | Proportion of Patients Achieving Complete Renal Response | 4 Participants |
| Placebo + Standard-of-care | Proportion of Patients Achieving Complete Renal Response | 3 Participants |
Secondary
Proportion of Patients Achieving Partial Renal Response (PRR)
Proportion of patients achieving PRR, defined as a: ≥50% reduction of UPCR from Baseline, and to \<1.0 if the Baseline UPCR was \<3.0 or to \<3.0 if the Baseline value was ≥3.0.
Time frame: Week 25 and Week 37
Population: Participants in the intent to treat set, defined as the set of all participants who are randomized to the study. This analysis focuses on the participants with Class III/IV ± Class V lupus nephritis. Due to the early termination of the study, not all participants reached the timepoints for efficacy analysis and no participants completed the full 52-week treatment period.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Zetomipzomib 30 mg + Standard-of-care | Proportion of Patients Achieving Partial Renal Response (PRR) | Week 25 | 5 Participants |
| Zetomipzomib 30 mg + Standard-of-care | Proportion of Patients Achieving Partial Renal Response (PRR) | Week 37 | 1 Participants |
| Zetomipzomib 60 mg + Standard-of-care | Proportion of Patients Achieving Partial Renal Response (PRR) | Week 25 | 8 Participants |
| Zetomipzomib 60 mg + Standard-of-care | Proportion of Patients Achieving Partial Renal Response (PRR) | Week 37 | 1 Participants |
| Placebo + Standard-of-care | Proportion of Patients Achieving Partial Renal Response (PRR) | Week 25 | 6 Participants |
| Placebo + Standard-of-care | Proportion of Patients Achieving Partial Renal Response (PRR) | Week 37 | 0 Participants |
Secondary
Proportion of Patients With UPCR ≤0.5
Proportion of patients with UPCR ≤0.5
Time frame: Week 13, Week 25, and Week 37
Population: Participants in the intent to treat set, defined as the set of all participants who are randomized to the study. This analysis focuses on the participants with Class III/IV ± Class V lupus nephritis. Due to the early termination of the study, not all participants reached the timepoints for efficacy analysis and no participants completed the full 52-week treatment period.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Zetomipzomib 30 mg + Standard-of-care | Proportion of Patients With UPCR ≤0.5 | Week 37 | 0 Participants |
| Zetomipzomib 30 mg + Standard-of-care | Proportion of Patients With UPCR ≤0.5 | Week 13 | 2 Participants |
| Zetomipzomib 30 mg + Standard-of-care | Proportion of Patients With UPCR ≤0.5 | Week 25 | 1 Participants |
| Zetomipzomib 60 mg + Standard-of-care | Proportion of Patients With UPCR ≤0.5 | Week 37 | 1 Participants |
| Zetomipzomib 60 mg + Standard-of-care | Proportion of Patients With UPCR ≤0.5 | Week 13 | 5 Participants |
| Zetomipzomib 60 mg + Standard-of-care | Proportion of Patients With UPCR ≤0.5 | Week 25 | 5 Participants |
| Placebo + Standard-of-care | Proportion of Patients With UPCR ≤0.5 | Week 37 | 0 Participants |
| Placebo + Standard-of-care | Proportion of Patients With UPCR ≤0.5 | Week 25 | 3 Participants |
| Placebo + Standard-of-care | Proportion of Patients With UPCR ≤0.5 | Week 13 | 2 Participants |
Secondary
Time to Complete Renal Response and Partial Renal Response
The comparison of the time to Complete Renal Response and Partial Renal Response for the zetomipzomib treatment groups (zetomipzomib 30mg and zetomipzomib 60mg) versus placebo. Hazard ratio (HR) and associated two-sided CIs are estimated using the Cox proportional hazards model. The model includes terms for treatment, the randomization stratification factors, and baseline UPCR (continuous).
Time frame: Baseline through Week 37
Population: Participants in the intent to treat set, defined as the set of all participants who are randomized to the study. This analysis focuses on the participants with Class III/IV ± Class V lupus nephritis. Due to the early termination of the study, not all participants reached the timepoints for efficacy analysis and no participants completed the full 52-week treatment period.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Zetomipzomib 30 mg + Standard-of-care | Time to Complete Renal Response and Partial Renal Response | Complete Renal Response | NA weeks |
| Zetomipzomib 30 mg + Standard-of-care | Time to Complete Renal Response and Partial Renal Response | Partial Renal Response | 24.3 weeks |
| Zetomipzomib 60 mg + Standard-of-care | Time to Complete Renal Response and Partial Renal Response | Complete Renal Response | 26.9 weeks |
| Zetomipzomib 60 mg + Standard-of-care | Time to Complete Renal Response and Partial Renal Response | Partial Renal Response | 12.6 weeks |
| Placebo + Standard-of-care | Time to Complete Renal Response and Partial Renal Response | Complete Renal Response | NA weeks |
| Placebo + Standard-of-care | Time to Complete Renal Response and Partial Renal Response | Partial Renal Response | 25.1 weeks |
Comparison: Time to complete renal response for zetomipzomib 30 mg + standard-of-care versus placebo + standard-of-care95% CI: [0.2, 3.3]
Comparison: Time to complete renal response for zetomipzomib 60 mg + standard-of-care versus placebo + standard-of-care95% CI: [0.7, 6.7]
Comparison: Time to partial renal response for zetomipzomib 30 mg + standard-of-care versus placebo + standard-of-care95% CI: [0.5, 3]
Comparison: Time to partial renal response zetomipzomib 60 mg + standard-of-care versus placebo + standard-of-care95% CI: [1.1, 5.9]
Post Hoc
Change in UPCR
Percentage change from Baseline in Urine Protein to Creatinine Ratio (UPCR) by visit
Time frame: Week 13, Week 25, and Week 37
Population: Participants in the intent to treat set defined as the participants with Class III/IV ± Class V lupus nephritis including the participant who was actually diagnosed as Class IV and was mistakenly stratified to Pure Class V. Due to the early termination of the study, not all participants reached the timepoints for efficacy analysis and no participants completed the full 52-week treatment period.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Zetomipzomib 30 mg + Standard-of-care | Change in UPCR | Week 25 | -37.27 percent change in 24-hr UPCR value | Standard Deviation 45 |
| Zetomipzomib 30 mg + Standard-of-care | Change in UPCR | Week 13 | -33.08 percent change in 24-hr UPCR value | Standard Deviation 34.37 |
| Zetomipzomib 30 mg + Standard-of-care | Change in UPCR | Week 37 | -68.39 percent change in 24-hr UPCR value | — |
| Zetomipzomib 60 mg + Standard-of-care | Change in UPCR | Week 25 | -61.56 percent change in 24-hr UPCR value | Standard Deviation 50.85 |
| Zetomipzomib 60 mg + Standard-of-care | Change in UPCR | Week 13 | -46.33 percent change in 24-hr UPCR value | Standard Deviation 55.16 |
| Zetomipzomib 60 mg + Standard-of-care | Change in UPCR | Week 37 | -72.59 percent change in 24-hr UPCR value | Standard Deviation 29.91 |
| Placebo + Standard-of-care | Change in UPCR | Week 13 | -34.63 percent change in 24-hr UPCR value | Standard Deviation 36.01 |
| Placebo + Standard-of-care | Change in UPCR | Week 37 | -23.08 percent change in 24-hr UPCR value | Standard Deviation 17.43 |
| Placebo + Standard-of-care | Change in UPCR | Week 25 | -40.33 percent change in 24-hr UPCR value | Standard Deviation 42.47 |
Post Hoc
Proportion of Participants With UPCR ≤0.5
Proportion of Participants With UPCR ≤0.5
Time frame: Week 13, Week 25, and Week 37
Population: Participants in the intent to treat set defined as the participants with Class III/IV ± Class V lupus nephritis including the participant who was actually diagnosed as Class IV and was mistakenly stratified to Pure Class V. Due to the early termination of the study, not all participants reached the timepoints for efficacy analysis and no participants completed the full 52-week treatment period.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Zetomipzomib 30 mg + Standard-of-care | Proportion of Participants With UPCR ≤0.5 | Week 25 | 1 Participants |
| Zetomipzomib 30 mg + Standard-of-care | Proportion of Participants With UPCR ≤0.5 | Week 13 | 2 Participants |
| Zetomipzomib 30 mg + Standard-of-care | Proportion of Participants With UPCR ≤0.5 | Week 37 | 0 Participants |
| Zetomipzomib 60 mg + Standard-of-care | Proportion of Participants With UPCR ≤0.5 | Week 25 | 5 Participants |
| Zetomipzomib 60 mg + Standard-of-care | Proportion of Participants With UPCR ≤0.5 | Week 13 | 5 Participants |
| Zetomipzomib 60 mg + Standard-of-care | Proportion of Participants With UPCR ≤0.5 | Week 37 | 1 Participants |
| Placebo + Standard-of-care | Proportion of Participants With UPCR ≤0.5 | Week 13 | 2 Participants |
| Placebo + Standard-of-care | Proportion of Participants With UPCR ≤0.5 | Week 37 | 0 Participants |
| Placebo + Standard-of-care | Proportion of Participants With UPCR ≤0.5 | Week 25 | 3 Participants |