Clinical trial NCT05138133: Phase 3 Study of Anifrolumab in Adult Patients With Active Proliferative Lupus Nephritis
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Lupus Nephritis
Keywords: Lupus Nephritis, anifrolumab, Systemic Lupus Erythematosus, intravenous
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2021-11-30
Enrollment: 360
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Difference in proportion of participants with CRR (Complete Renal Response) in anifrolumab group compared with placebo group
timeFrame: Week 52
Secondary outcomes:
measure: Difference in proportion of participants achieving sustained OCS reduction in anifrolumab group compared with placebo group.
timeFrame: from Week 24 through Week 52
measure: Hazard Ratio (HR) of achieving sustained CRR in anifrolumab compared with placebo group
timeFrame: baseline through Week 52
measure: Difference in the mean standardized AUC for UPCR between anifrolumab and placebo participants
timeFrame: baseline through Week 52
measure: 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
timeFrame: baseline through Week 52, baseline through Week 104
measure: Difference in proportion of participants achieving aCRR (Alternative Complete Renal Response)
timeFrame: Week 52
measure: Difference in the proportion of participants achieving CRR with sustained OCS reduction
timeFrame: Week 52
measure: Difference in the proportion of participants achieving CRR
timeFrame: Week 24
measure: HR of achieving sustained CRR in anifrolumab compared with placebo
timeFrame: baseline through Week 104
measure: HR of achieving 50% reduction in UPCR in anifrolumab compared to placebo group
timeFrame: baseline through Week 52
measure: Difference in mean UPCR between the anifrolumab and placebo group
timeFrame: Week 52
measure: PRR (Partial Renal Response)
timeFrame: Week 52
measure: Difference in change from baseline in extra-renal SLEDAI-2K total score
timeFrame: baseline through Week 104
measure: 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
timeFrame: Week 52
Other outcomes:
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country: Puerto Rico
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city: Chelyabinsk
country: Russian Federation
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city: Moscow
country: Russian Federation
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city: Moscow
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country: Russian Federation
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city: Adapazari
country: Turkey
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city: Ankara
country: Turkey
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city: Ankara
country: Turkey
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city: Ankara
country: Turkey
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city: Istanbul
country: Turkey
facility: Research Site
city: Istanbul
country: Turkey
facility: Research Site
city: Izmir
country: Turkey
facility: Research Site
city: Kahramanmaras
country: Turkey
facility: Research Site
city: Kayseri
country: Turkey
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city: Kocaeli
country: Turkey
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city: Ha Noi
country: Vietnam
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city: Hanoi
country: Vietnam
facility: Research Site
city: Hanoi
country: Vietnam
facility: Research Site
city: Ho Chi Minh
country: Vietnam
facility: Research Site
city: Hochiminh
country: Vietnam
facility: Research Site
Study officials:
References: