Study Comparing the Efficacy and Safety of Zetomipzomib in Patients with Active Lupus Nephritis
Research type
Research Study
Full title
A Phase 2b, Randomized, Controlled Double-blind, Multicenter Study Comparing the Efficacy and Safety of Zetomipzomib (KZR-616) 30 mg or 60 mg with Placebo in Patients with Active Lupus Nephritis
IRAS ID
1007650
Contact name
Michelle Greenman
Contact email
Sponsor organisation
Kezar Life Sciences, Inc.
Eudract number
2022-502227-22
Clinicaltrials.gov Identifier
Research summary
Research Summary
This is a Phase 2b, randomized, double-blind, placebo-controlled, global, multicenter study to evaluate efficacy and safety of zetomipzomib in patients with active Class III/IV +/-V LN or pure Class V.
Summary of Results
This trial took place in the following countries: Argentina, Brazil, China, Colombia, Greece, Guatemala, India, Malaysia, the Philippines, South Africa, the Republic of Korea, and the United States.
When was this study done: This trial started in March 2023 and ended prematurely in November 2024.
Study objective: The main goal of this study was to test how well and how safely a treatment called zetomipzomib (at a dose of 30 mg or 60 mg given as a weekly injection under the skin) worked for participants with active lupus nephritis, a kidney disease caused by lupus. This study also included participants who were treated with placebo (a treatment that looked the same as zetomipzomib but did not include any medicine). Because of the early stop to the study, the main focus of the study was safety, and only limited data on how well the treatment worked were analyzed.
WHAT PARTICIPANTS WERE INCLUDED IN THE TRIAL: Number of participants included in the trial by country
This study included 84 participants:
• 23 from India
• 14 from Argentina
• 10 from Malaysia
• 10 from the Philippines
• 7 from Guatemala
• 5 from Brazil
• 4 from Greece
• 4 from the United States
• 3 from China
• 2 from Colombia
• 1 from South Africa
• 1 from the Republic of Korea
Age group and gender breakdown: The average age of participants across all groups was 32 years. The age of participants ranged from 18 to 56 years. Of all participants, 92.9% were female and 7.1% were male.
Eligibility criteria: Participants had a serious kidney disease caused by their lupus, called lupus nephritis, which was confirmed by a kidney biopsy. Participants with Class III/IV ± V lupus nephritis had to have significant amount of protein in the urine that was at least equal to another substance called creatinine (a protein-to-creatinine ratio of 1.0 or higher). Participants with Class V lupus nephritis had to have protein levels in their urine that were even higher than the amount of creatinine (a protein-to-creatinine ratio of 2.0 or higher).
WHICH MEDICINES WERE STUDIED: The medicines evaluated in this study were zetomipzomib (at either a 30 mg or 60 mg dose) and a placebo. A placebo is a treatment that looks identical to the study drug, contains no medicine, and is administered the same way as the study drug, zetomipzomib.
Participants continued to take their standard-of-care medicine during the study.
WHAT WERE THE SIDE EFFECTS: The most common side effects in participants taking zetomipzomib were:
• Fever (32%)
• Injection site reactions (such as redness, swelling, or pain) (27%)
• Nausea (feeling sick to the stomach) (21%)
• Vomiting (20%)
• Loose stools (18%)
A small number of participants reported more serious side effects, such as infections, but these were rare.
WHAT WERE THE OVERALL RESULTS OF THE STUDY: The study was suspended after an independent group of experts recommended pausing the study due to deaths and serious adverse events (severe side effects and medical problems or changes) that occurred near the time of receiving zetomipzomib. The sponsor then ended the study early for business reasons.
Early results from the study showed promising signs of how well the treatment worked for participants with lupus nephritis, particularly for participants with Class III/IV ± V lupus nephritis. Many participants on the 60 mg zetomipzomib treatment had improvements in measures of their disease.
Unfortunately, four participants died during the study. Three of those deaths occurred in participants treated with zetomipzomib. These deaths may have been influenced by many factors, such as kidney problems related to the disease, heart-related issues, possible infections that existed before the study, and other medications they were taking. While these factors may have contributed to the participants’ deaths, a possible role of zetomipzomib could not be definitively ruled out.
The side effects were very similar between the two doses of zetomipzomib (30 mg and 60 mg).
HOW HAS THIS STUDY HELPED PATIENTS AND RESEARCHERS: Although the study ended earlier than planned, it provided valuable information. Some participants showed improvement in some disease measures of lupus nephritis after receiving treatment with zetomipzomib, especially at the 60 mg dose. This study also showed that the safety of zetomipzomib at 30 mg and 60 mg doses, given as a once weekly injection under the skin, was similar to what was seen in earlier studies. These results help researchers evaluate whether zetomipzomib should be studied further as a potential treatment for lupus nephritis and better understand its role in diseases where the immune system attacks the body.
ARE THERE PLANS FOR FURTHER STUDIES: Future studies are planned for zetomipzomib. More research is needed to confirm results of this study, and future studies will look at how zetomipzomib can be used safely and effectively in different illnesses caused by an overactive immune system.REC name
North of Scotland Research Ethics Committee 1
REC reference
23/NS/0066
Date of REC Opinion
25 Aug 2023
REC opinion
Further Information Favourable Opinion