The purpose of this study is to evaluate the efficacy and safety of IV antifrolumab in adult patients with Active Proliferative Lupus Nephritis
This Phase 3, multicenter, multinational, randomized, double-blind, placebo-controlled study with OLE is to evaluate the efficacy and safety of anifrolumab versus placebo as added to SOC (MMF and glucocorticoids) in adults with active proliferative Class III or Class IV LN (both with or without concomitant Class V). The total study duration may be up to approximately 142 weeks, including screening and follow-up. Double-blind period will be 76 weeks. Participants who complete double-blind treatment period may enter open-label extension to receive anifrolumab for up 52 weeks. Approximately 360 of the enrolled participants will be randomly assigned to study intervention (anifrolumab or placebo) at a ratio of 1:1 during double-blind treatment period.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
363
Anifrolumab intravenous infusion (IV)
Placebo intravenous infusion (IV)
Difference in proportion of participants with CRR (Complete Renal Response) in anifrolumab group compared with placebo group
CRR is defined as: * UPCR ≤ 0.5 mg/mg * eGFR ≥ 60 mL/min/1.73 m2 or no decrease from baseline of ≥ 20%
Time frame: Week 52
Difference in proportion of participants achieving sustained OCS reduction in anifrolumab group compared with placebo group
Sustained OCS reduction
Time frame: from Week 24 through Week 52
HR of achieving sustained CRR in anifrolumab compared with placebo group
The endpoint for deriving the summary measure is time to sustained CRR, defined as time to achieving CRR that is sustained from that time point through week 52
Time frame: baseline through Week 52
Difference in the mean standardized AUC for UPCR between anifrolumab and placebo participants
Proteinuria as measured by the cumulative UPCR
Time frame: baseline through Week 52
Difference in proportion of participants with CRR in anifrolumab group compared with placebo group
CRR at week 24
Time frame: Week 24
HR to summarize the difference in the risk of hazard of renal-related event or death at any given time between anifrolumab and placebo participants
Onset of renal-related event or death through Week 52
Time frame: Through Week 52
HR to summarize the difference in the risk of hazard of renal-related event or death at any given time between anifrolumab and placebo participants
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Research Site
Glendale, Arizona, United States
Research Site
La Palma, California, United States
Research Site
Los Angeles, California, United States
Research Site
Upland, California, United States
Research Site
Plantation, Florida, United States
Research Site
Atlanta, Georgia, United States
Research Site
Louisville, Kentucky, United States
Research Site
Summit, New Jersey, United States
Research Site
Manhasset, New York, United States
Research Site
New York, New York, United States
...and 154 more locations
Onset of renal-related event or death through Week 76
Time frame: Through Week 76
Difference between anifrolumab and placebo in proportions of participants who achieve aCRR
aCRR (alternative complete renal response) defined as; * UPCR ≤ 0.5 mg/mg * eGFR ≥ 90 mL/min/1.73 m2 or no decrease from baseline of ≥ 10%
Time frame: Week 52
Difference between anifrolumab and placebo in proportions of participants who achieve CRR with sustained OCS reduction
CRR at Week 52 with Sustained OCS Reduction
Time frame: Week 52
HR of achieving sustained CRR in anifrolumab compared to placebo group
Time to sustained CRR through the time frame period
Time frame: Through week 76
HR of achieving 50% reduction in UPCR in anifrolumab compared to placebo group
The endpoint for deriving the summary measure is time from the first dose of study intervention to achieving 50% reduction in UPCR
Time frame: Through Week 52
Difference in mean UPCR between the anifrolumab and placebo group
Proteinuria as measured by UPCR
Time frame: Week 52
Difference in proportion of participants achieving PRR (Partial Renal Response) in anifrolumab group compared with placebo group
PRR defined as: UPCR \<1.0 mg/mg (for participants with baseline UPCR ≤3 mg/mg) or \>50% improvement and ≤3 mg/mg (for participants with baseline UPCR \>3 mg/mg) eGFR ≥ 60 mL/min/1.73 m2 or no confirmed decrease of ≥20% from baseline
Time frame: Week 52
Difference in change from baseline in extra-renal SLEDAI-2K total score
The extra-renal SLEDAI-2K score is obtained by summing the SLEDAI-2K items without including the items within the renal system organ
Time frame: Through Week 76
Difference in mean change from baseline in domains and component scores of Short Form-36 Version 2 (SF-36v2) and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-fatigue) total score
To evaluate patient-reported HRQOL and health status
Time frame: Week 52