Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as KZR-616 Lyophile, zetomipzomib, zetomipzomib in open-label extension
KZR-616 · 4 trials · 5 indications
The number of patients who achieve complete biochemical response (CR), defined as normal ALT, AST, and IgG values (if IgG level is elevated at Baseline) with glucocorticoid dose not higher than starting dose (at Baseline), by Week 24 of the Double-Blind Treatment Period. Analyses were also conducted at Week 12, Week 16, and Week 20.
Proportion of participants who experience AEs (adverse events) and SAEs (serious adverse events) during the double-blind treatment period (DBTP) and the open-label extension (OLE).
Proportion of participants experiencing a disease flare among the participants who achieved a complete biochemical response (CR) during the double-blind treatment period.
The mean Total Improvement Score (TIS) at OLE Week 48, which ranges from 0 to 100 \[low of 0 to high of 100, where higher scores are better\]. The timeframe of 48 weeks was selected because it represented the maximum timeframe of dosing for the last patient enrolled as the study drug administration ended when the last patient enrolled completed 48 weeks of dosing.
The primary efficacy endpoint was mean change from start to end of zetomipzomib (KZR-616) Treatment Periods in the Total Improvement Score (TIS), which ranges from 0 to 100 \[low of 0 to high of 100, where higher scores are better\]. Mean change in TIS was calculated by comparing the Baseline and post Baseline observations for patients in both KZR-616 treatment periods combined. Note: TIS scores for placebo treatment periods are presented in this outcome measure but were not included in the primary outcome measure analysis.
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.
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.
| Arm | Type | Description |
|---|---|---|
| zetomipzomib + standard-of-care (glucocorticoids) | EXPERIMENTAL | Initial 30 mg dose of zetomipzomib, followed by weekly 60 mg doses of zetomipzomib, for the remaining 23 weeks of the treatment period. |
| placebo + standard-of-care (glucocorticoids) | PLACEBO_COMPARATOR | Initial 30 mg dose of placebo (sterile water for injection), followed by weekly 60 mg doses of placebo, for the remaining 23 weeks of the treatment period. |
| zetomipzomib + standard-of care (glucocorticoids) open-label extension period | EXPERIMENTAL | Initial 30 mg dose of zetomipzomib at the open-label extension (OLE) Week 1 visit, followed by weekly doses of 60 mg of zetomipzomib, for up to a total of 24 additional weeks of treatment. |
| KZR-616 45 mg + standard therapy (open-label) | EXPERIMENTAL | All patients received a SC injection of 30 mg KZR-616 at Visit 1 (Day 1), followed by weekly SC injections of 45 mg KZR-616 up to a maximum of 96 weeks. Study drug administration ended for all patients in Study KZR-616-003E when the last patient enrolled completed 48 weeks of dosing. |
| Arm A | OTHER | * Treatment Period 1: KZR-616 30 mg SC weekly for 2 weeks, then 45 mg SC weekly for 14 weeks * Treatment Period 2: Placebo SC weekly for 16 weeks |
| Arm B | OTHER | * Treatment Period 1: Placebo SC weekly for 16 weeks * Treatment Period 2: KZR-616 30 mg SC weekly for 2 weeks, then 45 mg SC weekly for 14 weeks |
| KZR-616 45 mg + standard of care therapy (Phase 1b) | EXPERIMENTAL | Dose escalation cohort of patients with SLE with and without nephritis to receive 45 mg dose level of KZR-616 in combination with standard of care therapy. Two Phase 1b cohorts received 45 mg at some point during the study. Cohort 1 received 45 mg zetomipzomib frozen maleate weekly for 13 weeks. Cohort 2a followed a step-up dosing procedure. Patients received zetomipzomib frozen maleate, 30 mg weekly for 2 weeks, followed by 45 mg weekly for 2 weeks then followed by 60 mg weekly for 9 weeks. KZR-616 was administered as a SC injection. |
| KZR-616 60 mg + standard of care therapy (Phase 1b) | EXPERIMENTAL | Dose escalation cohort of patients with SLE with and without nephritis to receive 60 mg dose level of KZR-616 in combination with standard of care therapy. Four Phase 1b cohorts received 60 mg at some point during the study. Cohort 2 received 60 mg zetomipzomib frozen maleate weekly for 13 weeks. Cohorts 2a, 2b, and 2c all followed a step-up dosing procedure. Patients in Cohort 2a received zetomipzomib frozen maleate, 30 mg weekly for 2 weeks, followed by 45 mg weekly for 2 weeks then followed by 60 mg weekly for 9 weeks. Patients in Cohort 2b received zetomipzomib lyophile, 30 mg weekly for 1 week, followed by 60 mg weekly for 12 weeks. Patients in Cohort 2c (tolerability strategies cohort) received zetomipzomib lyophile, 30 mg weekly for 1 week, followed by 60 mg weekly for 12 weeks. KZR-616 was administered as a SC injection. |
| KZR-616 75 mg + standard of care therapy (Phase 1b) | EXPERIMENTAL | Dose escalation cohort of patients with SLE with and without nephritis to receive 75 mg dose level of KZR-616 in combination with standard of care therapy. One Phase 1b cohort received 75 mg at some point during the study. Cohort 3 followed a step-up dosing procedure. Patients in Cohort 3 received zetomipzomib lyophile, 30 mg weekly for 1 week, followed by 75 mg weekly for 12 weeks. KZR-616 was administered as a SC injection. |
| KZR-616 60 mg + standard therapy (Phase 2) | EXPERIMENTAL | 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 standard therapy including at least one immunosuppressive agent. KZR-616 was administered as a SC injection weekly at a dose of 60 mg for 24 weeks (including a step-up from an initial Week 1 dose of 30 mg). \*\* See Limitations/Caveats for additional information |
| Name | Type | Description |
|---|---|---|
| zetomipzomib | DRUG | Subcutaneous injection of zetomipzomib with a target dose of 60 mg weekly |
| placebo | DRUG | Subcutaneous injection of placebo |
| zetomipzomib in open-label extension | DRUG | Subcutaneous injection of zetomipzomib with a target dose of 60 mg weekly |
| KZR-616 | DRUG | Subcutaneous 30 mg for 1 week, then 45 mg weekly |
Key Inclusion Criteria for the Double-blind Treatment Period: * Must be aged ≥18 years. * Must have a clinical diagnosis of AIH and signs of active disease despite standard-of-care therapy for ≥3 months or disease flare after experiencing complete remission induced by standard-of-care treatment,...
KZR-616 is an investigational small molecule developed by Kezar Life Sciences, Inc. (ticker KZR) for immunology indications. It has been studied in clinical trials in lupus nephritis, systemic lupus erythematosus, polymyositis, and dermatomyositis. It remains in clinical development and is not an approved therapy.
KZR-616 targets the immunoproteasome, a protein complex involved in immune cell protein degradation. By binding the immunoproteasome, the drug is designed to modulate immune signaling. This selective targeting distinguishes it from broad proteasome inhibitors, which act on both constitutive and immunoproteasome forms.
KZR-616 is being developed by Kezar Life Sciences, Inc., a clinical-stage biopharmaceutical company that trades under the ticker symbol KZR. Kezar has sponsored the clinical trial program for KZR-616 across lupus and inflammatory myopathy indications.
KZR-616 is in clinical development, with completed Phase 1 and Phase 2 trials. It is investigational and has not been approved by the FDA. The completed studies include a Phase 1 trial in systemic lupus erythematosus and lupus nephritis and Phase 2 trials in polymyositis and dermatomyositis.
KZR-616 has been studied in completed trials including NCT03393013, a Phase 1 study in SLE with and without lupus nephritis enrolling 69 patients, NCT04033926, a Phase 2 study in active polymyositis or dermatomyositis enrolling 25 patients, and NCT04628936, an open-label extension of the Phase 2 PRESIDIO crossover study enrolling 18 patients.
KZR-616 has been evaluated in lupus nephritis as part of a Phase 1 study, NCT03393013, which enrolled patients with systemic lupus erythematosus with and without lupus nephritis. That trial is completed. KZR-616 is investigational and is not approved for the treatment of lupus nephritis.