Lupus Nephritis
Conditions
Keywords
Lupus Nephritis, anifrolumab, Systemic Lupus Erythematosus, intravenous
Brief summary
The purpose of this study is to evaluate the efficacy and safety of IV antifrolumab in adult patients with Active Proliferative Lupus Nephritis
Detailed description
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.
Interventions
DRUGAnifrolumab
Anifrolumab intravenous infusion (IV)
DRUGPlacebo
Placebo intravenous infusion (IV)
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Double Blind (Participant, Care Provider and Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Active proliferative LN Class III or IV either with or without the presence of Class V according to the 2003 ISN/RPS classification 2. Renal biopsy obtained within 6 months prior to signing the ICF or during Screening Period. 3. Urine protein to creatinine ratio \> 1 mg/mg (113.17 mg/mmol) 4. eGFR ≥ 35 mL/min/1.73 m2 (as calculated by the Chronic Kidney Disease Epidemiology Collaboration formula). 5. Fulfills updated 2019 EULAR/ACR SLE classification criteria. 6. No signs of symptoms of active TB prior to or during screening or no treatment for latent TB
Exclusion criteria
1. A diagnosis of pure Class V LN based on the renal biopsy obtained within 6 months prior to signing the ICF or during Screening. 2. Known history of a primary immunodeficiency, splenectomy, or any underlying condition that predisposes the participant to infection, or a positive result for HIV confirmed by the central lab at Screening - an HIV test must be performed during Screening, and the result should be available prior to Week 0 (Day 1). 3. Evidence of hepatitis C or active hepatitis B. 4. Any history of cancer except sucessfully cured skin squamos or basal skin carcinoma and cervical cancer in situ. 5. Receipt of the following for the current LN flare (ie, since the qualifying renal biopsy): IV cyclophosphamide \> 2 pulses of high-dose (≥ 0.5 g/m2) or \> 4 doses of low dose (500 mg every 2 weeks) or Average MMF \> 2.5 g/day (or \> 1800 mg/day of enteric coated mycophenolate sodium) for more than 8 weeks or Tacrolimus \> 4 mg/day for more than 8 weeks; Cyclosporine for more than 8 weeks or during last 8 weeks prior to signing the ICF; Voclosporin for more than 8 weeks or during last 8 weeks prior to signing the ICF; Belimumab for more than 12 weeks or during last 12 weeks prior the ICF. 6. Previous receipt of \>◦2 investigation treatments (other than anifrolumab) for LN or SLE since time of diagnosis and through the ICF. 7. Known intolerance to ≤ 1.0 g/day of MMF. 8. Any history of severe COVID-19 infection.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Difference in proportion of participants with CRR (Complete Renal Response) in anifrolumab group compared with placebo group | Week 52 | CRR is defined as: * UPCR ≤ 0.5 mg/mg * eGFR ≥ 60 mL/min/1.73 m2 or no decrease from baseline of ≥ 20% |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Difference in proportion of participants achieving sustained OCS reduction in anifrolumab group compared with placebo group | from Week 24 through Week 52 | Sustained OCS reduction |
| HR of achieving sustained CRR in anifrolumab compared with placebo group | baseline through Week 52 | 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 |
| Difference in the mean standardized AUC for UPCR between anifrolumab and placebo participants | baseline through Week 52 | Proteinuria as measured by the cumulative UPCR |
| Difference in proportion of participants with CRR in anifrolumab group compared with placebo group | Week 24 | CRR at 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 | Through Week 52 | Onset of renal-related event or death through Week 52 |
| Difference between anifrolumab and placebo in proportions of participants who achieve aCRR | Week 52 | 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% |
| Difference between anifrolumab and placebo in proportions of participants who achieve CRR with sustained OCS reduction | Week 52 | CRR at Week 52 with Sustained OCS Reduction |
| HR of achieving sustained CRR in anifrolumab compared to placebo group | Through week 76 | Time to sustained CRR through the time frame period |
| HR of achieving 50% reduction in UPCR in anifrolumab compared to placebo group | Through Week 52 | The endpoint for deriving the summary measure is time from the first dose of study intervention to achieving 50% reduction in UPCR |
| Difference in mean UPCR between the anifrolumab and placebo group | Week 52 | Proteinuria as measured by UPCR |
| Difference in proportion of participants achieving PRR (Partial Renal Response) in anifrolumab group compared with placebo group | Week 52 | 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 |
| Difference in change from baseline in extra-renal SLEDAI-2K total score | Through Week 76 | The extra-renal SLEDAI-2K score is obtained by summing the SLEDAI-2K items without including the items within the renal system organ |
| 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 | Week 52 | To evaluate patient-reported HRQOL and health status |
Countries
Argentina, Belgium, Brazil, Bulgaria, China, Colombia, France, Germany, Hungary, India, Italy, Japan, Malaysia, Mexico, Netherlands, Peru, Poland, Puerto Rico, Russia, Taiwan, Thailand, Turkey (Türkiye), United States, Vietnam
Outcome results
None listed