Lupus Nephritis, Systemic Lupus Erythematosus
Conditions
Keywords
immunoproteasome inhibition, selective proteasome inhibition, proteasome, lupus nephritis, lupus, nephritis, active proliferative lupus nephritis, open-label, systemic lupus erythematosus, lupus erythematosus
Brief summary
This was a Phase 1b/2, multi-center study in which patients received KZR-616, administered as a subcutaneous (SC) injection weekly for 13 weeks (Phase 1b) or 24 weeks (Phase 2).
Detailed description
This was a Phase 1b/2, open-label, multi-center study in which patients received zetomipzomib administered as a SC injection weekly for either 13 weeks (Phase 1b) or for 24 weeks (Phase 2). In both phases, safety assessments continued for up to 12 weeks following the last dose of zetomipzomib. Phase 1b was an open-label, multiple dose escalation study designed to evaluate the safety and tolerability of escalating doses of zetomipzomib when administered in addition to standard-of-care therapy in patients with SLE with or without nephritis. For each cohort, at least 6 patients were to be enrolled to assure the availability of at least 4 evaluable patients. Decisions to escalate, expand, or decrease the dose level or dosing frequency following the first 4 weeks of dosing for at least 4 evaluable patients in a cohort were made following review by a data monitoring committee (DMC). The zetomipzomib formulations and doses administered by cohort in Phase 1b were: * Cohort 1: zetomipzomib frozen maleate, 45 mg weekly × 13 weeks * Cohort 2: zetomipzomib frozen maleate, 60 mg weekly × 13 weeks * Cohort 2a: zetomipzomib frozen maleate, 30 mg weekly × 2 weeks, followed by 45 mg weekly × 2 weeks, followed by 60 mg weekly × 9 weeks * Cohort 2b: zetomipzomib lyophile, 30 mg weekly × 1 week, followed by 60 mg weekly × 12 weeks * Cohort 2c: zetomipzomib lyophile, 30 mg weekly × 1 week, followed by 60 mg weekly × 12 weeks (tolerability strategies cohort) * Cohort 3: zetomipzomib lyophile, 30 mg weekly × 1 week, followed by 75 mg weekly × 12 weeks The Phase 2 portion of the open-label study was designed to evaluate the renal response, safety, and tolerability of a single dose level (60 mg) of zetomipzomib administered weekly in addition to standard therapy in patients with active proliferative lupus nephritis (LN) (Class III or IV, with or without Class V disease) with a UPCR ≥1.0. Patients must have been on standard therapy for LN including at least 1 immunosuppressive agent. Zetomipzomib was administered as a SC injection weekly for 24 weeks (including a step up from an initial Week 1 dose of 30 mg).
Interventions
DRUGKZR-616
Subcutaneous Injection of KZR-616
Sponsors
Kezar Life Sciences, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: Phase 1b: * Fulfilled the 2012 Systemic Lupus International Collaborating Clinics (SLICC) classification for SLE * Had a positive antinuclear antibody (ANA) titer, anti-double stranded DNA (dsDNA) antibody titer, or a positive anti-Smith antibody titer * Had active SLE (as indicated by Systemic Lupus Erythematosus Disease Activity Index 2000 \[SLEDAI-2K\] score ≥4), and * Had received at least 1 prior therapy for SLE Phase 2: * Had active proliferative LN (Class III or IV, with or without Class V disease) * Had a UPCR ≥1.0 measured in 24-hour urine collection * Had a histologic diagnosis of LN on renal biopsy within the prior 2 years; for biopsies \> 1 year before the Screening visit, one of the following must also be present at screening: low C3, low C4, or anti-ds-DNA elevated to above normal range * Fulfilled the 2012 SLICC classification for SLE * Had a positive ANA titer, anti-dsDNA antibody titer, or anti-Smith antibody titer, and * Were currently receiving ≥1 immunosuppressive agent at a stable dose and route of administration for ≥8 weeks. If the patient is also on corticosteroids then must be on a stable dose for ≥ 2 weeks prior to Baseline Key
Exclusion criteria
Phase 1b: * Current or medical history of: * Central nervous system manifestations by autoimmune disease * Overlapping autoimmune condition that may affect study assessments/outcomes * Antiphospholipid syndrome with history of thromboembolic event of within the 52 weeks prior to Screening * Malignancy of any type, with exceptions for in situ cancer that has been completely excised and certain cancers \>5 years ago * Positive test at Screening for HIV, hepatitis B/C * Major surgery within 4 weeks before signing informed consent form or planned major surgery during the study period Phase 2: * 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 * Malignancy of any type within the last 5 years, with exceptions for appropriately excised and cured cervical carcinoma in situ or excised basal or squamous cell carcinomas of the skin * Has received dialysis within the 52 weeks prior to Screening * Positive test at Screening for HIV, hepatitis B/C * Major surgery within 12 weeks before signing informed consent form or planned major surgery during the study period * Use of investigational therapy or device, and/or participation in an investigational trial \<8 weeks or 5 half-lives, whichever is longer, prior to Baseline; Patients who participated in Phase 1b of KZR-616-002 are excluded from Phase 2
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1b: Number of Patients Who Experienced at Least One Treatment-Related Treatment-Emergent Adverse Event | 25 weeks | The safety and tolerability of zetomipzomib (KZR-616) when administered as a subcutaneous injection weekly for 13 weeks in adult patients with systemic lupus erythematous (SLE) with and without nephritis, as assessed by number of patients who experienced at least one treatment-related treatment-emergent adverse event. For additional information about the safety and tolerability of KZR-616, please reference the adverse events section of this posting. |
| Phase 2: Number of Patients With Lupus Nephritis With a 50% Reduction in UPCR | 24 weeks | To assess the number of patients with lupus nephritis with a 50% reduction in UPCR after 24 weeks of weekly SC injections with KZR-616 when compared to baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1b: PK of KZR-616 (Tmax) | 8 hours | This is the time to maximum observed plasma concentration (tmax) observed after administration of KZR-616 at Week 5. The PK parameters were calculated using all timepoints at which the concentration was measured, ie. predose and 5, 15, 30 minutes, 1, 2, 4, and 8 hours postdose. |
| Phase 2: Number of Patients With a Partial Renal Response | 24 weeks | Number of patients with a partial renal response (PRR) after 24 weeks of treatment, as defined by: 1. For this outcome measure, Primary UPCR criterion was used (a 50% reduction of UPCR and reduction of UPCR to \<1.0 if baseline UPCR was \<3.0 (or reduction of UPCR to \<3.0 if baseline was ≥3.0)) 2. eGFR of greater than or equal to 60 mL/min/1.73 m\^2 or no worsening of eGFR from baseline of greater than or equal to 25% 3. No use of prohibited medication Count of patients below includes those who satisfy all three of the above criteria. |
| Phase 1b: PK of KZR-616 (AUC) | 8 hours | This is the area under the curve (AUC) from predose through 8 hour postdose observed after administration of KZR-616 at Week 5. The PK parameters were calculated using all timepoints at which the concentration was measured, ie. predose and 5, 15, 30 minutes, 1, 2, 4, and 8 hours postdose. |
| Phase 1b: Recommended Phase 2 Doses of Zetomipzomib When Administered as a Subcutaneous Injection | 25 weeks | The safety data from Phase 1b were used to determine a recommended dose of zetomipzomib to administer to patients with active proliferative lupus nephritis in Phase 2 of this study. As pre-specified in the study protocol, this outcome measure was to be determined qualitatively through discussion of relevant information from the Phase 1b portion of the trial at a data monitoring committee meeting. |
| Phase 2: Safety and Tolerability of KZR-616 When Administered as a SC Injection Weekly for 24 Weeks | 37 weeks | Exposure adjusted adverse event incidence rate for Injection Site Reactions and Systemic Injection Reactions. For additional information about the safety and tolerability of KZR-616, please reference the adverse events section of this posting. |
| Phase 1b: PK of KZR-616 (Cmax) | 8 hours | This is the maximum observed plasma concentration (Cmax) observed after administration of KZR-616 at Week 5. The PK parameters were calculated using all timepoints at which the concentration was measured, ie. predose and 5, 15, 30 minutes, 1, 2, 4, and 8 hours postdose. |
Countries
Australia, Colombia, Mexico, Peru, Poland, Russia, Ukraine, United States
Participant flow
Recruitment details
Patients who were enrolled in Phase 1b were ineligible to enroll in the Phase 2 portion of the study.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1, KZR-616 QW, 45 mg + SOC (Phase 1b) Dose escalation cohort of patients with SLE with and without nephritis to receive KZR-616 45 mg once weekly (QW) for 13 weeks in combination with standard of care (SOC) therapy.
KZR-616: Subcutaneous Injection of KZR-616 | 8 |
| Cohort 2, KZR-616 QW, 60 mg + SOC (Phase 1b) Dose escalation cohort of patients with SLE with and without nephritis to receive KZR-616 60 mg QW for 13 weeks in combination with SOC therapy.
KZR-616: Subcutaneous Injection of KZR-616 | 5 |
| Cohort 2a, KZR-616 QW, 30 mg x 2 Wks, 45 mg x 2 Wks, 60 mg x 9 Wks + SOC (Phase 1b) Dose escalation cohort of patients with SLE with and without nephritis to receive KZR-616 30 mg QW for 2 weeks, 45 mg QW for 2 weeks, and then 60 mg QW for 9 weeks in combination with SOC therapy.
KZR-616: Subcutaneous Injection of KZR-616 | 14 |
| Cohort 2b, KZR-616 QW, 30 mg x 1 wk, 60 mg x 12 Wks + SOC (Phase 1b) Dose escalation cohort of patients with SLE with and without nephritis to receive KZR-616 60 mg QW (following an initial Week 1 dose of 30 mg) for 12 weeks in combination with SOC therapy.
KZR-616: Subcutaneous Injection of KZR-616 | 6 |
| Cohort 2c, KZR-616 QW, 30 mg x 1 wk, 60 mg x 12 Wks + SOC (Phase 1b) Dose escalation cohort of patients with SLE with and without nephritis to receive KZR-616 60 mg QW (following an initial Week 1 dose of 30 mg) for 12 weeks in combination with SOC therapy.
This cohort was the tolerability strategy cohort, which introduced prophylactic measures of hydration with an oral electrolyte and non-sedating antihistamines for the first two doses.
KZR-616: Subcutaneous Injection of KZR-616 | 8 |
| Cohort 3, KZR-616 QW, 30 mg x 1 wk, 75 mg x 12 Wks + SOC (Phase 1b) Dose escalation cohort of patients with SLE with and without nephritis to receive KZR-616 75 mg QW (following an initial Week 1 dose of 30 mg) for 12 weeks in combination with SOC therapy.
KZR-616: Subcutaneous Injection of KZR-616 | 6 |
| KZR-616 QW, 60 mg + SOC (Phase 2) KZR-616 was administered as a subcutaneous injection QW for 24 weeks (including an initial Week 1 dose of 30 mg).
60 mg dose level of KZR-616 selected based on data from the Phase 1b dose escalation and administered to patients with active lupus nephritis in combination with SOC therapy including at least one immunosuppressive agent.
KZR-616: Subcutaneous Injection of KZR-616
\*See Limitations/Caveats for additional information | 22 |
| Total | 69 |
Baseline characteristics
| Characteristic | Cohort 1, KZR-616 QW, 45 mg + SOC (Phase 1b) | Cohort 2, KZR-616 QW, 60 mg + SOC (Phase 1b) | Cohort 2a, KZR-616 QW, 30 mg x 2 Wks, 45 mg x 2 Wks, 60 mg x 9 Wks + SOC (Phase 1b) | Cohort 2b, KZR-616 QW, 30 mg x 1 wk, 60 mg x 12 Wks + SOC (Phase 1b) | Cohort 2c, KZR-616 QW, 30 mg x 1 wk, 60 mg x 12 Wks + SOC (Phase 1b) | Cohort 3, KZR-616 QW, 30 mg x 1 wk, 75 mg x 12 Wks + SOC (Phase 1b) | KZR-616 QW, 60 mg + SOC (Phase 2) | Total |
|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 51.9 years STANDARD_DEVIATION 11.5 | 46.2 years STANDARD_DEVIATION 11.3 | 53.6 years STANDARD_DEVIATION 15.3 | 54.3 years STANDARD_DEVIATION 14.8 | 48.1 years STANDARD_DEVIATION 10.3 | 45.0 years STANDARD_DEVIATION 17.5 | 34.6 years STANDARD_DEVIATION 11.7 | 45.5 years STANDARD_DEVIATION 14.9 |
| eGFR Level at Baseline | — | — | — | — | — | — | 104.71 mL/min/1.73 m^2 STANDARD_DEVIATION 32.579 | 104.71 mL/min/1.73 m^2 STANDARD_DEVIATION 32.579 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 3 Participants | 10 Participants | 2 Participants | 5 Participants | 3 Participants | 12 Participants | 39 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants | 2 Participants | 4 Participants | 4 Participants | 3 Participants | 3 Participants | 10 Participants | 30 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 4 Participants | 4 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 2 Participants | 1 Participants | 2 Participants | 1 Participants | 3 Participants | 1 Participants | 11 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 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 | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 9 Participants | 9 Participants |
| Race (NIH/OMB) White | 7 Participants | 3 Participants | 12 Participants | 4 Participants | 7 Participants | 3 Participants | 7 Participants | 43 Participants |
| Sex: Female, Male Female | 8 Participants | 5 Participants | 12 Participants | 6 Participants | 8 Participants | 6 Participants | 20 Participants | 65 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 4 Participants |
| UPCR at Baseline | — | — | 3.85 mg/mg | — | 2.39 mg/mg | — | 2.50 mg/mg STANDARD_DEVIATION 2.56 | 2.55 mg/mg STANDARD_DEVIATION 2.46 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 5 | 0 / 14 | 0 / 6 | 0 / 8 | 0 / 6 | 0 / 22 |
| other Total, other adverse events | 8 / 8 | 5 / 5 | 12 / 14 | 4 / 6 | 7 / 8 | 3 / 6 | 22 / 22 |
| serious Total, serious adverse events | 0 / 8 | 1 / 5 | 2 / 14 | 1 / 6 | 0 / 8 | 0 / 6 | 2 / 22 |
Outcome results
Primary
Phase 1b: Number of Patients Who Experienced at Least One Treatment-Related Treatment-Emergent Adverse Event
The safety and tolerability of zetomipzomib (KZR-616) when administered as a subcutaneous injection weekly for 13 weeks in adult patients with systemic lupus erythematous (SLE) with and without nephritis, as assessed by number of patients who experienced at least one treatment-related treatment-emergent adverse event. For additional information about the safety and tolerability of KZR-616, please reference the adverse events section of this posting.
Time frame: 25 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1, KZR-616 QW, 45 mg + SOC (Phase 1b) | Phase 1b: Number of Patients Who Experienced at Least One Treatment-Related Treatment-Emergent Adverse Event | 7 Participants |
| Cohort 2, KZR-616 QW, 60 mg + SOC (Phase 1b) | Phase 1b: Number of Patients Who Experienced at Least One Treatment-Related Treatment-Emergent Adverse Event | 5 Participants |
| Cohort 2a, KZR-616 QW, 30 mg x 2 Wks, 45 mg x 2 Wks, 60 mg x 9 Wks + SOC (Phase 1b) | Phase 1b: Number of Patients Who Experienced at Least One Treatment-Related Treatment-Emergent Adverse Event | 11 Participants |
| Cohort 2b, KZR-616 QW, 30 mg x 1 wk, 60 mg x 12 Wks + SOC (Phase 1b) | Phase 1b: Number of Patients Who Experienced at Least One Treatment-Related Treatment-Emergent Adverse Event | 3 Participants |
| Cohort 2c, KZR-616 QW, 30 mg x 1 wk, 60 mg x 12 Wks + SOC (Phase 1b) | Phase 1b: Number of Patients Who Experienced at Least One Treatment-Related Treatment-Emergent Adverse Event | 6 Participants |
| Cohort 3, KZR-616 QW, 30 mg x 1 wk, 75 mg x 12 Wks + SOC (Phase 1b) | Phase 1b: Number of Patients Who Experienced at Least One Treatment-Related Treatment-Emergent Adverse Event | 3 Participants |
Primary
Phase 2: Number of Patients With Lupus Nephritis With a 50% Reduction in UPCR
To assess the number of patients with lupus nephritis with a 50% reduction in UPCR after 24 weeks of weekly SC injections with KZR-616 when compared to baseline.
Time frame: 24 weeks
Population: Outcome only measured for Phase 2.~One patient is excluded (N=21) due to enrollment under an earlier Protocol Amendment.~Prior to the open-label design, 1 patient was enrolled in Phase 2. Efficacy data for this patient are not included in this analysis because the patient received zetomipzomib for a shorter time duration (13 weeks) than specified by the outcome measure.~\*See Limitations and Caveats section for more information
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1, KZR-616 QW, 45 mg + SOC (Phase 1b) | Phase 2: Number of Patients With Lupus Nephritis With a 50% Reduction in UPCR | 11 Participants |
Secondary
Phase 1b: PK of KZR-616 (AUC)
This is the area under the curve (AUC) from predose through 8 hour postdose observed after administration of KZR-616 at Week 5. The PK parameters were calculated using all timepoints at which the concentration was measured, ie. predose and 5, 15, 30 minutes, 1, 2, 4, and 8 hours postdose.
Time frame: 8 hours
Population: This outcome was only measured in Phase 1b. The PK population is different than the overall studied population. As is pre-specified in the study protocol, analysis was completed per dose/treatment instead of per cohort for PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1, KZR-616 QW, 45 mg + SOC (Phase 1b) | Phase 1b: PK of KZR-616 (AUC) | 258 ng*h/ml | — |
| Cohort 2, KZR-616 QW, 60 mg + SOC (Phase 1b) | Phase 1b: PK of KZR-616 (AUC) | 387 ng*h/ml | Geometric Coefficient of Variation 38.1 |
| Cohort 2a, KZR-616 QW, 30 mg x 2 Wks, 45 mg x 2 Wks, 60 mg x 9 Wks + SOC (Phase 1b) | Phase 1b: PK of KZR-616 (AUC) | 430 ng*h/ml | Geometric Coefficient of Variation 36.8 |
| Cohort 2b, KZR-616 QW, 30 mg x 1 wk, 60 mg x 12 Wks + SOC (Phase 1b) | Phase 1b: PK of KZR-616 (AUC) | 636 ng*h/ml | Geometric Coefficient of Variation 31.7 |
Secondary
Phase 1b: PK of KZR-616 (Cmax)
This is the maximum observed plasma concentration (Cmax) observed after administration of KZR-616 at Week 5. The PK parameters were calculated using all timepoints at which the concentration was measured, ie. predose and 5, 15, 30 minutes, 1, 2, 4, and 8 hours postdose.
Time frame: 8 hours
Population: This outcome was only measured in Phase 1b. The PK population is different than the overall studied population. As is pre-specified in the study protocol, analysis was completed per dose/treatment instead of per cohort for PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1, KZR-616 QW, 45 mg + SOC (Phase 1b) | Phase 1b: PK of KZR-616 (Cmax) | 74.2 ng/mL | — |
| Cohort 2, KZR-616 QW, 60 mg + SOC (Phase 1b) | Phase 1b: PK of KZR-616 (Cmax) | 134 ng/mL | Geometric Coefficient of Variation 45.6 |
| Cohort 2a, KZR-616 QW, 30 mg x 2 Wks, 45 mg x 2 Wks, 60 mg x 9 Wks + SOC (Phase 1b) | Phase 1b: PK of KZR-616 (Cmax) | 151 ng/mL | Geometric Coefficient of Variation 50.3 |
| Cohort 2b, KZR-616 QW, 30 mg x 1 wk, 60 mg x 12 Wks + SOC (Phase 1b) | Phase 1b: PK of KZR-616 (Cmax) | 265 ng/mL | Geometric Coefficient of Variation 60.4 |
Secondary
Phase 1b: PK of KZR-616 (Tmax)
This is the time to maximum observed plasma concentration (tmax) observed after administration of KZR-616 at Week 5. The PK parameters were calculated using all timepoints at which the concentration was measured, ie. predose and 5, 15, 30 minutes, 1, 2, 4, and 8 hours postdose.
Time frame: 8 hours
Population: This outcome was only measured in Phase 1b. The PK population is different than the overall studied population. As is pre-specified in the study protocol, analysis was completed per dose/treatment instead of per cohort for PK data.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1, KZR-616 QW, 45 mg + SOC (Phase 1b) | Phase 1b: PK of KZR-616 (Tmax) | 1.00 hours |
| Cohort 2, KZR-616 QW, 60 mg + SOC (Phase 1b) | Phase 1b: PK of KZR-616 (Tmax) | 0.25 hours |
| Cohort 2a, KZR-616 QW, 30 mg x 2 Wks, 45 mg x 2 Wks, 60 mg x 9 Wks + SOC (Phase 1b) | Phase 1b: PK of KZR-616 (Tmax) | 0.25 hours |
| Cohort 2b, KZR-616 QW, 30 mg x 1 wk, 60 mg x 12 Wks + SOC (Phase 1b) | Phase 1b: PK of KZR-616 (Tmax) | 0.50 hours |
Secondary
Phase 1b: Recommended Phase 2 Doses of Zetomipzomib When Administered as a Subcutaneous Injection
The safety data from Phase 1b were used to determine a recommended dose of zetomipzomib to administer to patients with active proliferative lupus nephritis in Phase 2 of this study. As pre-specified in the study protocol, this outcome measure was to be determined qualitatively through discussion of relevant information from the Phase 1b portion of the trial at a data monitoring committee meeting.
Time frame: 25 weeks
Population: The DMC reviewed cumulative Phase 1b study data and provided a recommendation for the Phase 2 dose.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1, KZR-616 QW, 45 mg + SOC (Phase 1b) | Phase 1b: Recommended Phase 2 Doses of Zetomipzomib When Administered as a Subcutaneous Injection | 60 mg |
Secondary
Phase 2: Number of Patients With a Partial Renal Response
Number of patients with a partial renal response (PRR) after 24 weeks of treatment, as defined by: 1. For this outcome measure, Primary UPCR criterion was used (a 50% reduction of UPCR and reduction of UPCR to \<1.0 if baseline UPCR was \<3.0 (or reduction of UPCR to \<3.0 if baseline was ≥3.0)) 2. eGFR of greater than or equal to 60 mL/min/1.73 m\^2 or no worsening of eGFR from baseline of greater than or equal to 25% 3. No use of prohibited medication Count of patients below includes those who satisfy all three of the above criteria.
Time frame: 24 weeks
Population: Outcome only measured for Phase 2.~One patient is excluded (N=21) due to enrollment under an earlier Protocol Amendment.~Prior to the open-label design, 1 patient was enrolled in Phase 2. Efficacy data for this patient are not included in this analysis because the patient received zetomipzomib for a shorter time duration (13 weeks) than specified by the outcome measure.~\*See Limitations and Caveats section for more information
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1, KZR-616 QW, 45 mg + SOC (Phase 1b) | Phase 2: Number of Patients With a Partial Renal Response | 10 Participants |
Secondary
Phase 2: Safety and Tolerability of KZR-616 When Administered as a SC Injection Weekly for 24 Weeks
Exposure adjusted adverse event incidence rate for Injection Site Reactions and Systemic Injection Reactions. For additional information about the safety and tolerability of KZR-616, please reference the adverse events section of this posting.
Time frame: 37 weeks
Population: This outcome measure was only analyzed for Phase 2.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1, KZR-616 QW, 45 mg + SOC (Phase 1b) | Phase 2: Safety and Tolerability of KZR-616 When Administered as a SC Injection Weekly for 24 Weeks | Injection Site Reactions | 0.036 events per person-weeks |
| Cohort 1, KZR-616 QW, 45 mg + SOC (Phase 1b) | Phase 2: Safety and Tolerability of KZR-616 When Administered as a SC Injection Weekly for 24 Weeks | Systemic Injection Reactions | 0.045 events per person-weeks |
Post Hoc
Phase 1b: Changes in UPCR in Patients With SLE Who Had Active Lupus Nephritis
Changes in lupus disease assessments and changes from baseline in laboratory measures \- Renal parameters (UPCR) in Patients with SLE who had active lupus nephritis at baseline, 13 weeks (end of treatment), and 25 weeks (end of study)
Time frame: Week 25
Population: Only two patients in the Phase 1b study had active lupus nephritis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1, KZR-616 QW, 45 mg + SOC (Phase 1b) | Phase 1b: Changes in UPCR in Patients With SLE Who Had Active Lupus Nephritis | Baseline | 3.85 g/g |
| Cohort 1, KZR-616 QW, 45 mg + SOC (Phase 1b) | Phase 1b: Changes in UPCR in Patients With SLE Who Had Active Lupus Nephritis | Week 13 (End of Treatment) | 2.89 g/g |
| Cohort 1, KZR-616 QW, 45 mg + SOC (Phase 1b) | Phase 1b: Changes in UPCR in Patients With SLE Who Had Active Lupus Nephritis | Week 25 (End of Study) | 1.12 g/g |
| Cohort 2, KZR-616 QW, 60 mg + SOC (Phase 1b) | Phase 1b: Changes in UPCR in Patients With SLE Who Had Active Lupus Nephritis | Baseline | 2.39 g/g |
| Cohort 2, KZR-616 QW, 60 mg + SOC (Phase 1b) | Phase 1b: Changes in UPCR in Patients With SLE Who Had Active Lupus Nephritis | Week 13 (End of Treatment) | 0.69 g/g |
| Cohort 2, KZR-616 QW, 60 mg + SOC (Phase 1b) | Phase 1b: Changes in UPCR in Patients With SLE Who Had Active Lupus Nephritis | Week 25 (End of Study) | 1.47 g/g |