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

Lupus Nephritis Clinical Trial

— IRIS  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05138133
• Other study ID #: D3466C00001
• Secondary ID: 2021-002862-42
• Status: Recruiting
• Phase: Phase 3
• Start date: February 15, 2022
• Est. completion date: July 7, 2028

Study information

• Verified date: May 2024
• Source: AstraZeneca
• Contact: AstraZeneca Clinical Study Information Center
• Phone: 1-877-240-9479
• Email: information.center[@]astrazeneca.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 346
• Est. completion date: July 7, 2028
• Est. primary completion date: September 30, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Lupus Nephritis
• Nephritis

Intervention

Drug:
• Anifrolumab
Anifrolumab intravenous infusion (IV)
• Placebo
Placebo intravenous infusion (IV)

Locations

Country	Name	City	State
Argentina	Research Site	Buenos Aires
Argentina	Research Site	Caba
Argentina	Research Site	Cordoba
Argentina	Research Site	La Plata
Argentina	Research Site	Rosario
Argentina	Research Site	San Juan
Argentina	Research Site	San Miguel de Tucuman
Belgium	Research Site	Bruxelles
Belgium	Research Site	Leuven
Belgium	Research Site	Liège
Brazil	Research Site	Belo Horizonte
Brazil	Research Site	Maringá
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Recife
Brazil	Research Site	Salvador
Brazil	Research Site	Sao Jose Do Rio Preto
Brazil	Research Site	Sao Paulo
Brazil	Research Site	São Paulo
Bulgaria	Research Site	Plovdiv
Bulgaria	Research Site	Plovdiv
Bulgaria	Research Site	Sofia
Bulgaria	Research Site	Sofia
Bulgaria	Research Site	Sofia
China	Research Site	Beijing
China	Research Site	Beijing
China	Research Site	Chengdu
China	Research Site	Guangzhou
China	Research Site	Guangzhou
China	Research Site	Haikou
China	Research Site	Hangzhou
China	Research Site	Jinan
China	Research Site	Jining
China	Research Site	Nanchang
China	Research Site	Nanjing
China	Research Site	Nanjing
China	Research Site	Nanning
China	Research Site	Shanghai
China	Research Site	Shanghai
China	Research Site	Shanghai
China	Research Site	Shengyang
China	Research Site	Shenzhen
China	Research Site	Tianjin
China	Research Site	Wuhan
China	Research Site	Wuxi
China	Research Site	Xi'an
China	Research Site	Zhengzhou City
Colombia	Research Site	Barranquilla
Colombia	Research Site	Cali
Colombia	Research Site	Medellin
France	Research Site	Aurillac Cedex
France	Research Site	Bordeaux Cedex
France	Research Site	Marseille
France	Research Site	Paris
France	Research Site	Paris
France	Research Site	Paris
France	Research Site	STRASBOURG Cedex
France	Research Site	Toulouse
Germany	Research Site	Dresden
Germany	Research Site	Düsseldorf
Germany	Research Site	Essen
Germany	Research Site	Goettingen
Germany	Research Site	Hannover
Germany	Research Site	Heidelberg
Germany	Research Site	Kirchheim
Germany	Research Site	Köln
Germany	Research Site	Mainz Am Rhein
Germany	Research Site	Stuttgart
Hungary	Research Site	Budapest
Hungary	Research Site	Budapest
Hungary	Research Site	Budapest
Hungary	Research Site	Debrecen
Hungary	Research Site	Pécs
India	Research Site	Ahmedabad
India	Research Site	Ahmedabad
India	Research Site	Dehradun
India	Research Site	Delhi
India	Research Site	Delhi
India	Research Site	Delhi
India	Research Site	Gurugram
India	Research Site	Nadiad
India	Research Site	New Delhi
India	Research Site	New Delhi
India	Research Site	New Delhi
India	Research Site	Pune
India	Research Site	Secunderabad
India	Research Site	Vijayawada
India	Research Site	Visakapatnam
Italy	Research Site	Ancona
Italy	Research Site	Brescia
Italy	Research Site	Cona
Italy	Research Site	Monza
Italy	Research Site	Padova
Italy	Research Site	Roma
Italy	Research Site	Roma
Japan	Research Site	Bunkyo-ku
Japan	Research Site	Chiba-shi
Japan	Research Site	Chuo-ku
Japan	Research Site	Fukuoka-shi
Japan	Research Site	Gifu-shi
Japan	Research Site	Hiroshima-shi
Japan	Research Site	Izumo-shi
Japan	Research Site	Kita-gun
Japan	Research Site	Kitakyushu-shi
Japan	Research Site	Matsumoto-shi
Japan	Research Site	Nagasaki-shi
Japan	Research Site	Okayama
Japan	Research Site	Ono
Japan	Research Site	Osaka-shi
Japan	Research Site	Sagamihara-shi
Japan	Research Site	Sapporo-shi
Japan	Research Site	Sendai-shi
Japan	Research Site	Shinagawa-ku
Japan	Research Site	Shinjuku-ku
Japan	Research Site	Shinjuku-ku
Japan	Research Site	Toyoake-shi
Malaysia	Research Site	Batu Caves
Malaysia	Research Site	Ipoh
Malaysia	Research Site	Kajang
Malaysia	Research Site	Kuala Lumpur
Malaysia	Research Site	Kuantan
Malaysia	Research Site	Taiping
Mexico	Research Site	Chihuahua
Mexico	Research Site	Guadalajara
Mexico	Research Site	Guadalajara
Mexico	Research Site	Mexico
Mexico	Research Site	México
Mexico	Research Site	San Luis Potosi
Netherlands	Research Site	Amsterdam
Peru	Research Site	Bellavista
Peru	Research Site	Lima
Peru	Research Site	Lima
Peru	Research Site	Lima
Peru	Research Site	Lima
Peru	Research Site	Lima
Peru	Research Site	Lima
Peru	Research Site	Lima
Peru	Research Site	Piura
Poland	Research Site	Bydgoszcz
Poland	Research Site	Lódz
Poland	Research Site	Nadarzyn
Poland	Research Site	Olsztyn
Poland	Research Site	Opole
Poland	Research Site	Poznan
Poland	Research Site	Poznan
Poland	Research Site	Rzeszów
Poland	Research Site	Szczecin
Poland	Research Site	Wroclaw
Poland	Research Site	Wroclaw
Russian Federation	Research Site	Chelyabinsk
Russian Federation	Research Site	Krasnoyarsk
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Novosibirsk
Russian Federation	Research Site	Orenburg
Russian Federation	Research Site	St. Petersburg
Taiwan	Research Site	Kaohsiung
Taiwan	Research Site	New Taipei City
Taiwan	Research Site	Taichung
Taiwan	Research Site	Taichung
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taipei City
Taiwan	Research Site	Taoyuan
Thailand	Research Site	Bangkok
Thailand	Research Site	Bangkok
Thailand	Research Site	Hat Yai
Thailand	Research Site	Muang
Thailand	Research Site	Ratchathewi
Turkey	Research Site	Ankara
Turkey	Research Site	Ankara
Turkey	Research Site	Ankara
Turkey	Research Site	Istanbul
Turkey	Research Site	Istanbul
Turkey	Research Site	Izmir
Turkey	Research Site	Kahramanmaras
Turkey	Research Site	Kayseri
Turkey	Research Site	Kocaeli
United States	Research Site	Allen	Texas
United States	Research Site	Atlanta	Georgia
United States	Research Site	Birmingham	Alabama
United States	Research Site	Colleyville	Texas
United States	Research Site	Danville	Pennsylvania
United States	Research Site	Edinburg	Texas
United States	Research Site	El Paso	Texas
United States	Research Site	Glendale	Arizona
United States	Research Site	Great Neck	New York
United States	Research Site	Hallandale Beach	Florida
United States	Research Site	Houston	Texas
United States	Research Site	La Jolla	California
United States	Research Site	Las Cruces	New Mexico
United States	Research Site	Las Vegas	Nevada
United States	Research Site	Loma Linda	California
United States	Research Site	Los Angeles	California
United States	Research Site	Louisville	Kentucky
United States	Research Site	Manhasset	New York
United States	Research Site	Middleburg Heights	Ohio
United States	Research Site	New Haven	Connecticut
United States	Research Site	New York	New York
United States	Research Site	New York	New York
United States	Research Site	Newark	New Jersey
United States	Research Site	Newark	Delaware
United States	Research Site	Orange	California
United States	Research Site	Plantation	Florida
United States	Research Site	Saint Louis	Missouri
United States	Research Site	Summit	New Jersey
United States	Research Site	Sun City Center	Florida
United States	Research Site	Upland	California
United States	Research Site	Winston-Salem	North Carolina
Vietnam	Research Site	Ha Noi
Vietnam	Research Site	Hanoi
Vietnam	Research Site	Hanoi
Vietnam	Research Site	Ho Chi Minh
Vietnam	Research Site	Hochiminh

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

United States,  Vietnam,  Argentina,  Belgium,  Brazil,  Bulgaria,  China,  Colombia,  France,  Germany,  Hungary,  India,  Italy,  Japan,  Malaysia,  Mexico,  Netherlands,  Peru,  Poland,  Russian Federation,  Taiwan,  Thailand,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	Difference in the mean standardized AUC for UPCR between anifrolumab and placebo participants	Proteinuria as measured by the cumulative UPCR	baseline through Week 52
Secondary	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
Secondary	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
Secondary	Difference in the proportion of participants achieving CRR with sustained OCS reduction	CRR with sustained OCS reduction	Week 52
Secondary	Difference in the proportion of participants achieving CRR	Early onset of CRR	Week 24
Secondary	HR of achieving sustained CRR in anifrolumab compared with placebo	Time to sustained CRR through the time frame period	baseline through Week 104
Secondary	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
Secondary	Difference in mean UPCR between the anifrolumab and placebo group	Proteinuria as measured by UPCR	Week 52
Secondary	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
Secondary	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
Secondary	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