Phase 3 Study of Anifrolumab in Adult Patients With Active Proliferative Lupus Nephritis

Study Overview
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Brief Summary
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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
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This is a Phase 3, multicenter, multinational, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of anifrolumab versus placebo as added to SOC (consisting of 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 116 weeks, including the Screening and Follow-up. Approximately 360 participants will be randomized in a 1:1 ratio to receive anifrolumab or matching placebo throughout during the Treatment Period.

Official Title
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A Multicentre Randomized Double-Blind Placebo Controlled Phase 3 Study to Evaluate the Efficacy and Safety of Anifrolumab in Adult Patients With Active Proliferative Lupus Nephritis

Conditions
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Lupus Nephritis

Intervention / Treatment
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* Drug: Anifrolumab
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Active proliferative LN Class III or IV either with or without the presence of Class V according to the 2003 ISN/RPS classification Renal biopsy obtained within 6 months prior to signing the ICF or during Screening Period. Urine protein to creatinine ratio > 1 mg/mg (113.17 mg/mmol) eGFR ≥ 35 mL/min/1.73 m2 (as calculated by the Chronic Kidney Disease Epidemiology Collaboration formula). Fulfills updated 2019 EULAR/ACR SLE classification criteria. No signs of symptoms of active TB prior to or during screening or no treatment for latent TB Exclusion Criteria: A diagnosis of pure Class V LN based on the renal biopsy obtained within 6 months prior to signing the ICF or during Screening. 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). Evidence of hepatitis C or active hepatitis B. Any history of cancer except sucessfully cured skin squamos or basal skin carcinoma and cervical cancer in situ. 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. Previous receipt of >◦2 investigation treatments (other than anifrolumab) for LN or SLE since time of diagnosis and through the ICF. Known intolerance to ≤ 1.0 g/day of MMF. Any history of severe COVID-19 infection.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Anifrolumab<br>Solution for intravenous infusion | Drug: Anifrolumab<br>* Anifrolumab intravenous infusion (IV)<br>* Other names: Medi-546;|
| Placebo Comparator: Placebo<br>Solution for intravenous infusion | Drug: Placebo<br>* Placebo intravenous infusion (IV)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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% | Week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in proportion of participants achieving sustained OCS reduction in anifrolumab group compared with placebo group. | Sustained OCS reduction | from Week 24 through Week 52 | 
| Hazard Ratio (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 the end of the time frame period. | baseline through Week 52 | 
| Difference in the mean standardized AUC for UPCR between anifrolumab and placebo participants | Proteinuria as measured by the cumulative UPCR | baseline 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 | The endpoint for deriving the summary measure is time to onset of renal-related event or death. Time to onset of renal event as defined as any of the following: ESKD, doubling of serum creatinine, renal worsening as evidenced by increased proteinuria and/or renal function impairment, or 4) renal disease treatment failure or death | baseline through Week 52, baseline through Week 104 | 
| Difference in proportion of participants achieving aCRR (Alternative Complete Renal Response) | aCRR is defined as: UPCR ≤ 0.5 mg/mg; eGFR ≥ 90 mL/min/1.73 m2 or no confirmed decrease of eGFR from baseline of ≥ 10%. | Week 52 | 
| Difference in the proportion of participants achieving CRR with sustained OCS reduction | CRR with sustained OCS reduction | Week 52 | 
| Difference in the proportion of participants achieving CRR | Early onset of CRR | Week 24 | 
| HR of achieving sustained CRR in anifrolumab compared with placebo | Time to sustained CRR through the time frame period | baseline through Week 104 | 
| 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 | baseline through Week 52 | 
| Difference in mean UPCR between the anifrolumab and placebo group | Proteinuria as measured by UPCR | Week 52 | 
| PRR (Partial Renal Response) | PRR defined as: UPCR: - For participants with a baseline UPCR ≤3 mg/mg: <1.0 mg/mgb eGFR: ≥ 60 mL/min/1.73 m2 or no confirmed decrease of eGFR from baseline of ≥ 20% | 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. | baseline through Week 104 | 
| 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 | Week 52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lupus Nephritis, anifrolumab, Systemic Lupus Erythematosus, intravenous