A Phase 2 interventional study of zetomipzomib and placebo in Lupus Nephritis, sponsored by Kezar Life Sciences, Inc.. Terminated at 50 sites in 12 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-12-05.
Sponsored by Kezar Life Sciences, Inc. · Phase 2, Interventional, and Treatment
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).
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.
340 studies on the registry are indexed under Lupus Nephritis; 135 are open to participants now.
This study's enrollment of 84 is above the median of 48 across 242 interventional studies indexed under Lupus Nephritis.
Browse Lupus Nephritis studies →Kezar Life Sciences, Inc. is the lead sponsor of 7 studies on the registry; none are open to participants now.
Of its 6 completed or terminated interventional studies of FDA-regulated products, 6 (100%) have results posted.
Counted across the registry records on this site, refreshed daily.
Key Inclusion Criteria:
Key Exclusion Criteria:
Current or medical history of:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
BMI (body mass index)
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Biopsy and archival tissue
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Autoimmune disease
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Platelets
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis B tests
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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.
Drug: zetomipzomib
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.
Drug: zetomipzomib
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.
Drug: placebo
Subcutaneous injection of zetomipzomib
Also known as: KZR-616
Subcutaneous injection of placebo
Also known as: matching placebo
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
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
Proportion of Patients Achieving Complete Renal Response
Proportion of patients achieving complete renal response (CRR)
Time frame: Week 25
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
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
Proportion of Patients With UPCR ≤0.5
Proportion of patients with UPCR ≤0.5
Time frame: Week 13, Week 25, and Week 37
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
| Milestone | Zetomipzomib 30 mg + Standard-of-care | Zetomipzomib 60 mg + Standard-of-care | Placebo + Standard-of-care |
|---|---|---|---|
| Started | 27 | 29 | 28 |
| Completed | 0 | 0 | 0 |
| Not completed | 27 | 29 | 28 |
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.
| Participants | Zetomipzomib 30 mg + Standard-of-care | Zetomipzomib 60 mg + Standard-of-care | Placebo + Standard-of-care |
|---|---|---|---|
| Proportion of Patients Achieving Complete Renal Response | 0 | 1 | 0 |
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.
| Participants | Zetomipzomib 30 mg + Standard-of-care | Zetomipzomib 60 mg + Standard-of-care | Placebo + Standard-of-care |
|---|---|---|---|
| Week 25 | 5 | 8 | 6 |
| Week 37 | 1 | 1 | 0 |
Proportion of patients achieving complete renal response (CRR)
| Participants | Zetomipzomib 30 mg + Standard-of-care | Zetomipzomib 60 mg + Standard-of-care | Placebo + Standard-of-care |
|---|---|---|---|
| Proportion of Patients Achieving Complete Renal Response | 1 | 4 | 3 |
Percentage change from Baseline in Urine Protein to Creatinine Ratio (UPCR) by visit
| percent change in 24-hr UPCR value | Zetomipzomib 30 mg + Standard-of-care | Zetomipzomib 60 mg + Standard-of-care | Placebo + Standard-of-care |
|---|---|---|---|
| Week 13 | -33.08 ± 34.37 | -46.33 ± 55.16 | -32.27 ± 35.24 |
| Week 25 | -37.27 ± 45.00 | -61.56 ± 50.85 | -40.33 ± 42.47 |
| Week 37 | -68.39 ± NA | -72.59 ± 29.91 | -23.08 ± 17.43 |
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).
| weeks | Zetomipzomib 30 mg + Standard-of-care | Zetomipzomib 60 mg + Standard-of-care | Placebo + Standard-of-care |
|---|---|---|---|
| Complete Renal Response | NA (NA to NA) | 26.9 (24.1 to NA) | NA (NA to NA) |
| Partial Renal Response | 24.3 (12.6 to NA) | 12.6 (12.1 to 24.0) | 25.1 (12.4 to NA) |
Proportion of patients with UPCR ≤0.5
| Participants | Zetomipzomib 30 mg + Standard-of-care | Zetomipzomib 60 mg + Standard-of-care | Placebo + Standard-of-care |
|---|---|---|---|
| Week 13 | 2 | 5 | 2 |
| Week 25 | 1 | 5 | 3 |
| Week 37 | 0 | 1 | 0 |
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.
| percent change of SLEDAI-2K score | Zetomipzomib 30 mg + Standard-of-care | Zetomipzomib 60 mg + Standard-of-care | Placebo + Standard-of-care |
|---|---|---|---|
| Week 13 | -14.0 ± 45.4 | -56.4 ± 24.1 | -19.5 ± 33.7 |
| Week 25 | -18.6 ± 45.9 | -59.2 ± 33.6 | -27.2 ± 32.6 |
| Week 37 | -28.6 ± NA | -36.4 ± 51.4 | -5.0 ± 32.8 |
Percentage change from Baseline in Urine Protein to Creatinine Ratio (UPCR) by visit
| percent change in 24-hr UPCR value | Zetomipzomib 30 mg + Standard-of-care | Zetomipzomib 60 mg + Standard-of-care | Placebo + Standard-of-care |
|---|---|---|---|
| Week 13 | -33.08 ± 34.37 | -46.33 ± 55.16 | -34.63 ± 36.01 |
| Week 25 | -37.27 ± 45.00 | -61.56 ± 50.85 | -40.33 ± 42.47 |
| Week 37 | -68.39 ± NA | -72.59 ± 29.91 | -23.08 ± 17.43 |
Proportion of Participants With UPCR ≤0.5
| Participants | Zetomipzomib 30 mg + Standard-of-care | Zetomipzomib 60 mg + Standard-of-care | Placebo + Standard-of-care |
|---|---|---|---|
| Week 13 | 2 | 5 | 2 |
| Week 25 | 1 | 5 | 3 |
| Week 37 | 0 | 1 | 0 |
Collected over Through end of study visit, up to 52 weeks. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Zetomipzomib 30 mg + Standard-of-care | 2/27 (7.4%) | 5/27 (18.5%) | 23/27 (85.2%) |
| Zetomipzomib 60 mg + Standard-of-care | 1/29 (3.4%) | 8/29 (27.6%) | 25/29 (86.2%) |
| Placebo + Standard-of-care | 1/28 (3.6%) | 3/28 (10.7%) | 17/28 (60.7%) |
| Event | Zetomipzomib 30 mg + Standard-of-care | Zetomipzomib 60 mg + Standard-of-care | Placebo + Standard-of-care |
|---|---|---|---|
| DehydrationMetabolism and nutrition disorders | 0/27 | 2/29 | 0/28 |
| Cardiac failureCardiac disorders | 1/27 | 0/29 | 0/28 |
| Generalised oedemaGeneral disorders | 1/27 | 0/29 | 0/28 |
| PneumoniaInfections and infestations | 1/27 | 0/29 | 0/28 |
| Pseudomonas infectionInfections and infestations | 1/27 | 0/29 | 0/28 |
| Injection related reactionInjury, poisoning and procedural complications | 1/27 | 0/29 | 0/28 |
| Acute respiratory distress syndromeRespiratory, thoracic and mediastinal disorders | 1/27 | 0/29 | 0/28 |
| Gastroenteritis salmonellaInfections and infestations | 0/27 | 0/29 | 1/28 |
| HypokalaemiaMetabolism and nutrition disorders | 0/27 | 0/29 | 1/28 |
| Metabolic acidosisMetabolism and nutrition disorders | 0/27 | 0/29 | 1/28 |
| Event | Zetomipzomib 30 mg + Standard-of-care | Zetomipzomib 60 mg + Standard-of-care | Placebo + Standard-of-care |
|---|---|---|---|
| PyrexiaGeneral disorders | 6/27 | 12/29 | 2/28 |
| Injection site reactionGeneral disorders | 4/27 | 11/29 | 0/28 |
| VomitingGastrointestinal disorders | 2/27 | 9/29 | 2/28 |
| NauseaGastrointestinal disorders | 4/27 | 8/29 | 1/28 |
| Upper respiratory tract infectionInfections and infestations | 6/27 | 2/29 | 1/28 |
| ChillsGeneral disorders | 0/27 | 6/29 | 0/28 |
| DiarrhoeaGastrointestinal disorders | 5/27 | 5/29 | 3/28 |
| NasopharyngitisInfections and infestations | 1/27 | 4/29 | 0/28 |
| HeadacheNervous system disorders | 3/27 | 4/29 | 2/28 |
| CoughRespiratory, thoracic and mediastinal disorders | 1/27 | 4/29 | 1/28 |
Among the 11 participants who were stratified to Pure Class V LN, one was actually diagnosed as Class IV and was mistakenly stratified to Pure Class V. All primary and secondary outcome measures are presented as stratified, whereas the post-hoc outcome measures include the participant who was stratified incorrectly.
| Age, Continuous(years) | Zetomipzomib 30 mg + Standard-of-care | Zetomipzomib 60 mg + Standard-of-care | Placebo + Standard-of-care | Total |
|---|---|---|---|---|
| Mean | 31.0 ± 10.54 | 32.5 ± 9.44 | 32.8 ± 9.10 | 32.1 ± 9.61 |
| Sex: Female, Male(Participants) | Zetomipzomib 30 mg + Standard-of-care | Zetomipzomib 60 mg + Standard-of-care | Placebo + Standard-of-care | Total |
|---|---|---|---|---|
| Female | 25 | 28 | 25 | 78 |
| Male | 2 | 1 | 3 | 6 |
| Ethnicity (NIH/OMB)(Participants) | Zetomipzomib 30 mg + Standard-of-care | Zetomipzomib 60 mg + Standard-of-care | Placebo + Standard-of-care | Total |
|---|---|---|---|---|
| Hispanic or Latino | 5 | 10 | 13 | 28 |
| Not Hispanic or Latino | 22 | 19 | 15 | 56 |
| Unknown or Not Reported | 0 | 0 | 0 | 0 |
| Race (NIH/OMB)(Participants) | Zetomipzomib 30 mg + Standard-of-care | Zetomipzomib 60 mg + Standard-of-care | Placebo + Standard-of-care | Total |
|---|---|---|---|---|
| American Indian or Alaska Native | 1 | 5 | 2 | 8 |
| Asian | 19 | 15 | 13 | 47 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 | 0 |
| Black or African American | 1 | 1 | 3 | 5 |
| White | 6 | 7 | 9 | 22 |
| More than one race | 0 | 0 | 0 | 0 |
| Unknown or Not Reported | 0 | 1 | 1 | 2 |
| Average 24-hour UPCR at Screening(Participants) | Zetomipzomib 30 mg + Standard-of-care | Zetomipzomib 60 mg + Standard-of-care | Placebo + Standard-of-care | Total |
|---|---|---|---|---|
| ≤3.0 mg/mg | 13 | 15 | 13 | 41 |
| >3.0 mg/mg | 14 | 14 | 15 | 43 |
| Average 24-hour UPCR at Baseline(mg/mg) | Zetomipzomib 30 mg + Standard-of-care | Zetomipzomib 60 mg + Standard-of-care | Placebo + Standard-of-care | Total |
|---|---|---|---|---|
| Mean | 3.7 ± 2.0 | 3.6 ± 2.1 | 3.1 ± 1.6 | 3.5 ± 1.9 |
| SLEDAI-2K(score on a scale) | Zetomipzomib 30 mg + Standard-of-care | Zetomipzomib 60 mg + Standard-of-care | Placebo + Standard-of-care | Total |
|---|---|---|---|---|
| Mean | 11.8 ± 5.28 | 11.7 ± 5.48 | 10.5 ± 5.02 | 11.3 ± 5.23 |
| Time from SLE diagnosis to Screening(years) | Zetomipzomib 30 mg + Standard-of-care | Zetomipzomib 60 mg + Standard-of-care | Placebo + Standard-of-care | Total |
|---|---|---|---|---|
| Mean | 4.7 ± 5.0 | 8.1 ± 6.2 | 6.7 ± 5.8 | 6.5 ± 5.8 |
2 further baseline measures are reported on the registry.
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: No
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Studies of the drug tested here: KZR-616
Kezar Life Sciences, Inc.