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

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

The purpose of this study is to evaluate the efficacy and safety of IV antifrolumab in adult patients with Active Proliferative Lupus Nephritis

Study Overview

• Status: Active, not recruiting
• Conditions: Lupus Nephritis
• Intervention / Treatment: Drug: Anifrolumab; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 359
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • CABA, Argentina, C1425EOE
    • Research Site
  • Ciudad de Buenos Aires, Argentina, C1015ABO
    • Research Site
  • La Plata, Argentina, 1900
    • Research Site
  • Rosario, Argentina, S2000PBJ
    • Research Site
  • San Juan, Argentina, 5400
    • Research Site
• Belgium
  • Brussels, Belgium, 1200
    • Research Site
  • Leuven, Belgium, 3000
    • Research Site
  • Liège, Belgium, 4000
    • Research Site
• Brazil
  • Belo Horizonte, Brazil, 30130 100
    • Research Site
  • Campinas, Brazil, 13087-567
    • Research Site
  • Cuiabá, Brazil, 78020-500
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  • Maringá, Brazil, 87060-040
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  • Porto Alegre, Brazil, 90035-903
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  • Recife, Brazil, 50740-465
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  • Salvador, Brazil, 40150-150
    • Research Site
  • São José do Rio Preto, Brazil, 15090-000
    • Research Site
  • São Paulo, Brazil, 04014-002
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  • São Paulo, Brazil, 04036-002
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  • São Paulo, Brazil, 05403-9000
    • Research Site
• Bulgaria
  • Plovdiv, Bulgaria, 4002
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  • Sofia, Bulgaria, 1431
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• China
  • Beijing, China, 100034
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  • Beijing, China, 100044
    • Research Site
  • Bengbu, China, 233004
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  • Chengdu, China, 610072
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  • Guangzhou, China, 510530
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  • Haikou, China, 570311
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  • Hangzhou, China, 310009
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  • Jinan, China, 250021
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  • Jining, China, 272011
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  • Nanchang, China, 330006
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  • Nanjing, China, 210009
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  • Nanjing, China, 210029
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  • Nanning, China, 530021
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  • Shanghai, China, 200025
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  • Shanghai, China, 200040
    • Research Site
  • Shengyang, China, 110004
    • Research Site
  • Shenzhen, China, 518036
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  • Shijiazhuang, China, 050001
    • Research Site
  • Tianjin, China, 300201
    • Research Site
  • Wuhan, China, 430060
    • Research Site
  • Wuxi, China, 214023
    • Research Site
  • Xi'an, China, 710061
    • Research Site
  • Zhengzhou, China, 450000
    • Research Site
• Colombia
  • Barranquilla, Colombia, 080020
    • Research Site
  • Medellín, Colombia, 050010
    • Research Site
  • Medellín, Colombia, 050025
    • Research Site
• France
  • Aurillac, France, 15002
    • Research Site
  • Bordeaux, France, 33076
    • Research Site
  • Marseille, France, 13005
    • Research Site
  • Paris, France, 75018
    • Research Site
  • Paris, France, 75013
    • Research Site
  • Paris, France, 75679
    • Research Site
  • Strasbourg, France, 67098
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  • Toulouse, France, 31059
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• Germany
  • Cologne, Germany, 50937
    • Research Site
  • Dresden, Germany, 1307
    • Research Site
  • Hanover, Germany, 30625
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  • Heidelberg, Germany, 69120
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  • Kirchheim, Germany, 73230
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  • Mainz Am Rhein, Germany, 55131
    • Research Site
• Hungary
  • Budapest, Hungary, 1085
    • Research Site
  • Budapest, Hungary, 1097
    • Research Site
  • Debrecen, Hungary, 4032
    • Research Site
• India
  • Ahmedabad, India, 382421
    • Research Site
  • Ahmedabad, India, 380005
    • Research Site
  • Dehradun, India, 248001
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  • Delhi, India, 110029
    • Research Site
  • Hyderabad, India, 500082
    • Research Site
  • Kolkata, India, 700020
    • Research Site
  • Nadiād, India, 387001
    • Research Site
  • Pune, India, 411001
    • Research Site
  • Secunderabad, India, 500003
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  • Vijayawada, India, 522002
    • Research Site
  • Visakapatnam, India, 530013
    • Research Site
• Italy
  • Ancona, Italy, 60126
    • Research Site
  • Bologna, Italy, 40138
    • Research Site
  • Cona, Italy, 44124
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  • Eboli, Italy, 84025
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  • Padua, Italy, 35128
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  • Roma, Italy, 00161
    • Research Site
• Japan
  • Bunkyō City, Japan, 113-8655
    • Research Site
  • Chiba, Japan, 260-8712
    • Research Site
  • Hiroshima, Japan, 734-8551
    • Research Site
  • Kita-gun, Japan, 761-0793
    • Research Site
  • Kitakyushu-shi, Japan, 807-8555
    • Research Site
  • Matsumoto-shi, Japan, 390-8621
    • Research Site
  • Nagasaki, Japan, 852-8501
    • Research Site
  • Okayama, Japan, 700-8558
    • Research Site
  • Ono, Japan, 675-1392
    • Research Site
  • Sagamihara-shi, Japan, 252-0375
    • Research Site
  • Sendai, Japan, 980-0872
    • Research Site
  • Shinagawa-ku, Japan, 142-0054
    • Research Site
  • Shinjuku-ku, Japan, 160-8582
    • Research Site
  • Shinjuku-ku, Japan, 162-8655
    • Research Site
  • Shinjuku-ku, Japan, 162-8666
    • Research Site
  • Toyoake-shi, Japan, 470-1192
    • Research Site
• Malaysia
  • Batu Caves, Malaysia, 68100
    • Research Site
  • Ipoh, Malaysia, 30450
    • Research Site
  • Kajang, Malaysia, 43000
    • Research Site
  • Kuala Lumpur, Malaysia, 59100
    • Research Site
  • Kuantan, Malaysia, 25100
    • Research Site
  • Taiping, Malaysia, 34000
    • Research Site
• Mexico
  • Chihuahua City, Mexico, 31000
    • Research Site
  • Guadalajara, Mexico, 44650
    • Research Site
  • Guadalajara, Mexico, 44160
    • Research Site
  • México, Mexico, 06726
    • Research Site
  • México, Mexico, 14080
    • Research Site
  • San Luis Potosí City, Mexico, 78290
    • Research Site
• Netherlands
  • Amsterdam, Netherlands, 1105 AZ
    • Research Site
• Peru
  • Lima, Peru, LIMA 27
    • Research Site
  • Lima, Peru, LIMA 29
    • Research Site
  • Lima, Peru, 15023
    • Research Site
  • Lima, Peru, 15046
    • Research Site
  • Lima, Peru, 15102
    • Research Site
  • Lima, Peru, L34
    • Research Site
• Poland
  • Lodz, Poland, 92-213
    • Research Site
  • Olsztyn, Poland, 10-561
    • Research Site
  • Opole, Poland, 46-020
    • Research Site
  • Poznan, Poland, 60-355
    • Research Site
  • Poznan, Poland, 61-545
    • Research Site
  • Rzeszów, Poland, 35-301
    • Research Site
  • Warsaw, Poland, 02-006
    • Research Site
• Puerto Rico
  • Caguas, Puerto Rico, 00725
    • Research Site
• Russia
  • Moscow, Russia, 115522
    • Research Site
• Taiwan
  • Kaohsiung City, Taiwan, 833
    • Research Site
  • New Taipei City, Taiwan, 220
    • Research Site
  • Taichung, Taiwan, 40705
    • Research Site
  • Taichung, Taiwan, 40447
    • Research Site
  • Taipei, Taiwan, 235
    • Research Site
  • Taipei, Taiwan, 11217
    • Research Site
  • Taipei, Taiwan, 114
    • Research Site
• Thailand
  • Bangkok, Thailand, 10330
    • Research Site
  • Bangkok, Thailand, 10220
    • Research Site
  • Hat Yai, Thailand, 90110
    • Research Site
  • Muang, Thailand, 50200
    • Research Site
  • Ratchathewi, Thailand, 10400
    • Research Site
• Turkey (Türkiye)
  • Adapazarı, Turkey (Türkiye), 54290
    • Research Site
  • Ankara, Turkey (Türkiye), 06100
    • Research Site
  • Ankara, Turkey (Türkiye)
    • Research Site
  • Istanbul, Turkey (Türkiye)
    • Research Site
  • Istanbul, Turkey (Türkiye), 34865
    • Research Site
  • Izmir, Turkey (Türkiye), 35965
    • Research Site
  • Kahramanmaraş, Turkey (Türkiye), 46100
    • Research Site
  • Kayseri, Turkey (Türkiye), 38039
    • Research Site
  • Kocaeli, Turkey (Türkiye), 41380
    • Research Site
• United States
  • Arizona
    • Glendale, Arizona, United States, 85306
      • Research Site
  • California
    • La Palma, California, United States, 90623
      • Research Site
    • Los Angeles, California, United States, 90095
      • Research Site
    • Upland, California, United States, 91786
      • Research Site
  • Florida
    • Plantation, Florida, United States, 33324
      • Research Site
  • Georgia
    • Atlanta, Georgia, United States, 30308
      • Research Site
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Research Site
  • New Jersey
    • Summit, New Jersey, United States, 07901
      • Research Site
  • New York
    • Manhasset, New York, United States, 11030
      • Research Site
    • New York, New York, United States, 10016
      • Research Site
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Research Site
  • Ohio
    • Middleburg Heights, Ohio, United States, 44130
      • Research Site
  • Texas
    • Colleyville, Texas, United States, 76034
      • Research Site
    • Edinburg, Texas, United States, 78539
      • Research Site
    • El Paso, Texas, United States, 79902
      • Research Site
    • Houston, Texas, United States, 77054
      • Research Site
• Vietnam
  • Hanoi, Vietnam, 100000
    • Research Site
  • Hanoi, Vietnam, 10000
    • Research Site
  • Ho Chi Minh City, Vietnam, 700000
    • Research Site
  • Hochiminh, Vietnam, 70000
    • Research Site
  • Hà Nội, Vietnam, 100000
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Anifrolumab; Solution for intravenous infusion	Drug: Anifrolumab; Anifrolumab intravenous infusion (IV); Other Names: Medi-546
Placebo Comparator: Placebo; Solution for intravenous infusion	Drug: Placebo; Placebo intravenous infusion (IV)

What is the study measuring?

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 the mean standardized AUC for UPCR between anifrolumab and placebo participants	Proteinuria as measured by the cumulative UPCR	baseline through Week 52
Difference in mean UPCR between the anifrolumab and placebo group	Proteinuria as measured by UPCR	Week 52
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
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
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	baseline through Week 52
Difference in proportion of participants with CRR in anifrolumab group compared with placebo group	CRR at week 24	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	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	Onset of renal-related event or death through Week 76	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%	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	Week 52
HR of achieving sustained CRR in anifrolumab compared to placebo group	Time to sustained CRR through the time frame period	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	Through 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	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	Through Week 76

Collaborators and Investigators

• Sponsor: AstraZeneca

Publications and helpful links

General Publications

• Avasare R, Drexler Y, Caster DJ, Mitrofanova A, Jefferson JA. Management of Lupus Nephritis: New Treatments and Updated Guidelines. Kidney360. 2023 Oct 1;4(10):1503-1511. doi: 10.34067/KID.0000000000000230.

Study record dates

Study Major Dates

• Study Start (Actual): February 15, 2022
• Primary Completion (Estimated): February 26, 2027
• Study Completion (Estimated): December 5, 2028

Study Registration Dates

• First Submitted: November 17, 2021
• First Submitted That Met QC Criteria: November 17, 2021
• First Posted (Actual): November 30, 2021

Study Record Updates

• Last Update Posted (Actual): February 24, 2026
• Last Update Submitted That Met QC Criteria: February 23, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Lupus Nephritis, anifrolumab, Systemic Lupus Erythematosus, intravenous
• Additional Relevant MeSH Terms: Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Glomerulonephritis; Nephritis; Skin and Connective Tissue Diseases; Lupus Erythematosus, Systemic; Lupus Nephritis; Substandard Drugs; Pharmaceutical Preparations; anifrolumab
• Other Study ID Numbers: D3466C00001; 2021-002862-42 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Yes, indicates that AZ are accepting requests for IPD, but this does not mean that all requests will be shared.

• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No