Safety and Efficacy of Two Doses of Anifrolumab Compared to Placebo in Adult Subjects With Active Proliferative Lupus Nephritis

NCT ID: NCT02547922

Last Updated: 2021-11-24

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

147 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-11-04

Study Completion Date

2021-01-18

Brief Summary

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The purpose of this study is to evaluate the efficacy and safety of an intravenous treatment regimen of two doses of anifrolumab versus placebo in adult subjects with active proliferative lupus nephritis (LN).

Detailed Description

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This is a Phase 2, multicentre, multinational, randomised, double-blind, placebo-controlled study to evaluate the efficacy and safety of two intravenous (IV) treatment regimens of anifrolumab versus placebo while taking standard of care (SOC) treatment with mycophenolate mofetil (MMF) and corticosteroids in adult subjects with active proliferative lupus nephritis (LN).

Conditions

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Lupus Nephritis

Keywords

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lupus, nephritis, randomized, placebo, anifrolumab, safety, efficacy, adult

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Anifrolumab - Lower Dose

Anifrolumab - Lower Dose

Group Type EXPERIMENTAL

Anifrolumab

Intervention Type BIOLOGICAL

Administration every 4 week from Week 0 to Week 100 in addition to SOC which will continue until Week 112

Anifrolumab - Higher Dose

Anifrolumab - Higher Dose

Group Type EXPERIMENTAL

Anifrolumab

Intervention Type BIOLOGICAL

Administration every 4 week from Week 0 to Week 100 in addition to SOC which will continue until Week 112

Placebo

Placebo IV Q4W plus SOC

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Administration every 4 week from Week 0 to Week 100 in addition to SOC which will continue until Week 112

Interventions

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Anifrolumab

Administration every 4 week from Week 0 to Week 100 in addition to SOC which will continue until Week 112

Intervention Type BIOLOGICAL

Placebo

Administration every 4 week from Week 0 to Week 100 in addition to SOC which will continue until Week 112

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. Age 18 through 70 years at the time of screening
2. Fulfils at least 4 of the 11 criteria of the revised 1982 ACR classification criteria for SLE, at least one of which must be:

1. Positive antinuclear antibody (ANA) test (1:40 or higher) or
2. Elevated anti-dsDNA antibodies at screening (reported as equivocal or positive results), as per the centrallaboratory; or
3. Anti-Smith antibody at screening elevated to above normal (ie, positive or equivocal results) as per the central laboratory
3. Class III (±Class V) or Class IV (±Class V) LN according to the World Health Organisation (WHO) or 2003 ISN/RPS classification based on a renal biopsy obtained within 12 weeks prior to signing the ICF or during the screening period:
4. Urine protein to creatinine ratio \>1 gm/gm (113.17 mg/mmol), obtained on a 24-hour urine collection at screening
5. Estimated glomerular filtration rate ≥35 mL/min/1.73 m2
6. Must not have active or latent TB on either chest radiograph or by Quantiferon gold test
7. Women of childbearing potential must have a negative serum beta-hCG test at screening and negative urine pregnancy test prior to the first dose of sponsor-provided MMF.

Exclusion Criteria

1. Receipt of any investigational product (small molecule or biologic) or commercially available biologic agent within four weeks or 5 half lives prior to signing of the ICF, whichever is greater
2. Pure Class V membranous LN on a renal biopsy obtained within 12 weeks prior to signing ICF or during the screening period
3. Known intolerance to ≤1.0 gm/day of MMF
4. History of dialysis within 12 months prior to signing the ICF or expected need for renal replacement therapy (dialysis or renal transplant) within a 6 month period after enrolment
5. Subjects, who at the time of signing the ICF, received any of the following immunosuppressive therapies after their qualifying biopsy

1. Oral corticosteroids \>0.5 mg/kg/day for more than 8 weeks or
2. Oral or IV pulse methylprednisolone \>3.0 gm (cumulative dose) or
3. IV cyclophosphamide \>2 pulses of high-dose (≥0.5 gm/m2) or \>4 doses of low dose (500 mg every 2 weeks) or
4. Average MMF \>2.5 gm/day (\>1800 mg/day of enteric-coated mycophenolate sodium) for more than 8 weeks or
5. Tacrolimus \>4 mg/day for more than 8 weeks
6. Major surgery within 8 weeks before signing the ICF or major surgery planned during the study period
7. History of any non-SLE disease that has required treatment with oral or parenteral corticosteroids for more than a total of 2 weeks within the last 24 weeks prior to signing the ICF
8. Confirmed positive test for hepatitis B or hepatitis C
9. Any severe herpes infection at any time prior to randomization
10. Opportunistic infection requiring hospitalisation or parenteral antimicrobial treatment within 3 years prior to randomization (vaginal, oral and skin candidiasis is not an exclusionreason).
11. History of cancer, apart from:

1. Squamous or basal cell carcinoma of the skin that has been successfully treated
2. Cervical cancer in situ that has been successfully treated
12. Concurrent enrolment in another clinical study with an IP within 4 weeks prior to ICF signing or within 5 half-lives of the IP used in that clinical study, whichever is longer.
13. During screening (within 30 days before Day 1 \[Week 0 visit\]), any of the following:

1. Aspartate transaminase (AST) \>2.5×upper limit of normal (ULN)
2. Alanine transaminase (ALT) \>2.5×ULN
3. Total bilirubin \>ULN (unless due to Gilbert's syndrome \[based on Investigator's judgement\])
4. Glycosylated haemoglobin (HbA1c) \>8% (or \>0.08) at screening (diabetic subjects only)
5. Neutrophil count \<1x103/μL (or \<1.0 GI/L)
6. Platelet count \<25x103/μL (or \<25 GI/L)
7. Haemoglobin \<8 g/dL (or \<80 g/L).
Minimum Eligible Age

18 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Parexel

INDUSTRY

Sponsor Role collaborator

AstraZeneca

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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AstraZeneca AB

Role: STUDY_DIRECTOR

AstraZeneca

Locations

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Glendale, Arizona, United States

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Phoenix, Arizona, United States

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La Jolla, California, United States

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Los Angeles, California, United States

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Thousand Oaks, California, United States

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Aurora, Colorado, United States

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DeBary, Florida, United States

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Boston, Massachusetts, United States

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Newark, New Jersey, United States

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Great Neck, New York, United States

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New Hyde Park, New York, United States

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New York, New York, United States

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New York, New York, United States

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The Bronx, New York, United States

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Columbus, Ohio, United States

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Oklahoma City, Oklahoma, United States

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Memphis, Tennessee, United States

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Buenos Aires, , Argentina

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Córdoba, , Argentina

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Rosario, , Argentina

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Adelaide, , Australia

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Clayton, , Australia

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Parkville, , Australia

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Westmead, , Australia

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Brussels, , Belgium

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Brussels, , Belgium

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Leuven, , Belgium

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Liège, , Belgium

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Bordeaux, , France

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Marseille, , France

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Paris, , France

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Strasbourg, , France

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Toulouse, , France

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Berlin, , Germany

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Kiel, , Germany

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Budapest, , Hungary

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Debrecen, , Hungary

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Kaposvár, , Hungary

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Szeged, , Hungary

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Milan, , Italy

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Padua, , Italy

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Pisa, , Italy

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Reggio Emilia, , Italy

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Chihuahua City, , Mexico

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Guadalajara, , Mexico

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Guadalajara, , Mexico

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México, , Mexico

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San Luis Potosí City, , Mexico

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Arequipa, , Peru

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Lima, , Peru

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Lima, , Peru

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Lima, , Peru

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Lima, , Peru

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Lima, , Peru

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Lima, , Peru

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Lima, , Peru

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Lima, , Peru

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Krakow, , Poland

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Lodz, , Poland

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Warsaw, , Poland

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Orenburg, , Russia

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Saint Petersburg, , Russia

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Saint Petersburg, , Russia

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Belgrade, , Serbia

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Belgrade, , Serbia

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Niš, , Serbia

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Novi Sad, , Serbia

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Gwangju, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Suwon, , South Korea

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Barcelona, , Spain

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Barcelona, , Spain

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Changhua, , Taiwan

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Kaohsiung City, , Taiwan

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Taichung, , Taiwan

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Taichung, , Taiwan

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Taipei, , Taiwan

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Taoyuan, , Taiwan

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London, , United Kingdom

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Countries

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South Africa United States Argentina Australia Belgium France Germany Hungary Italy Mexico Peru Poland Russia Serbia South Korea Spain Taiwan United Kingdom

References

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Jayne D, Rovin B, Mysler E, Furie R, Houssiau F, Trasieva T, Knagenhjelm J, Schwetje E, Tang W, Tummala R, Lindholm C. Anifrolumab in lupus nephritis: results from second-year extension of a randomised phase II trial. Lupus Sci Med. 2023 Aug;10(2):e000910. doi: 10.1136/lupus-2023-000910.

Reference Type DERIVED
PMID: 37607780 (View on PubMed)

Jayne D, Rovin B, Mysler EF, Furie RA, Houssiau FA, Trasieva T, Knagenhjelm J, Schwetje E, Chia YL, Tummala R, Lindholm C. Phase II randomised trial of type I interferon inhibitor anifrolumab in patients with active lupus nephritis. Ann Rheum Dis. 2022 Apr;81(4):496-506. doi: 10.1136/annrheumdis-2021-221478. Epub 2022 Feb 10.

Reference Type DERIVED
PMID: 35144924 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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D3461C00007

Identifier Type: -

Identifier Source: org_study_id