NCT02547922

Brief Summary

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).

Trial Health

98
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
147

participants targeted

Target at P75+ for phase_2

Timeline
Completed

Started Nov 2015

Longer than P75 for phase_2

Geographic Reach
17 countries

80 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

August 31, 2015

Completed
14 days until next milestone

First Posted

Study publicly available on registry

September 14, 2015

Completed
2 months until next milestone

Study Start

First participant enrolled

November 4, 2015

Completed
4.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 26, 2019

Completed
1.1 years until next milestone

Study Completion

Last participant's last visit for all outcomes

January 18, 2021

Completed
10 months until next milestone

Results Posted

Study results publicly available

November 24, 2021

Completed
Last Updated

November 24, 2021

Status Verified

October 1, 2021

Enrollment Period

4.1 years

First QC Date

August 31, 2015

Results QC Date

September 7, 2021

Last Update Submit

October 28, 2021

Conditions

Keywords

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

Outcome Measures

Primary Outcomes (1)

  • Change From Baseline in 24-hour Urine Protein to Creatinine Ratio (UPCR)

    To evaluate the efficacy of anifrolumab plus SOC (combination of mycophenolate mofetil and corticosteroids) compared with placebo plus SOC in subjects with active proliferative lupus nephritis (LN). Geometric mean ratio of 24-hour UPCR at week 52 over baseline. Values \<1 indicate improvement from baseline.

    From Week 1 (Baseline) up to Week 52

Secondary Outcomes (1)

  • Proportion of Subjects Achieving the Composite Endpoint Complete Renal Response (CRR)

    Week 52

Other Outcomes (4)

  • Number of Subjects With Adverse Events

    From screening (Day-30 to -1) period until the follow-up period (Week 112)

  • Number of Subjects With Suicidal Ideation and Behavior and Suicide Attempts Via Columbia-Suicide Severity Rating Scale (C-SSRS)

    Baseline, treatment and follow up (an average of 60 weeks)

  • Total Score of Personal Health Questionnaire Depression Scale-8 (PHQD-8)

    Baseline, Week 12, Week 24, Week 36, Week 52, Week 60

  • +1 more other outcomes

Study Arms (3)

Anifrolumab - Lower Dose

EXPERIMENTAL

Anifrolumab - Lower Dose

Biological: Anifrolumab

Anifrolumab - Higher Dose

EXPERIMENTAL

Anifrolumab - Higher Dose

Biological: Anifrolumab

Placebo

PLACEBO COMPARATOR

Placebo IV Q4W plus SOC

Drug: Placebo

Interventions

AnifrolumabBIOLOGICAL

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

Anifrolumab - Higher DoseAnifrolumab - Lower Dose

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

Placebo

Eligibility Criteria

Age18 Years - 70 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Age 18 through 70 years at the time of screening
  • Fulfils at least 4 of the 11 criteria of the revised 1982 ACR classification criteria for SLE, at least one of which must be:
  • Positive antinuclear antibody (ANA) test (1:40 or higher) or
  • Elevated anti-dsDNA antibodies at screening (reported as equivocal or positive results), as per the centrallaboratory; or
  • Anti-Smith antibody at screening elevated to above normal (ie, positive or equivocal results) as per the central laboratory
  • 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:
  • Urine protein to creatinine ratio \>1 gm/gm (113.17 mg/mmol), obtained on a 24-hour urine collection at screening
  • Estimated glomerular filtration rate ≥35 mL/min/1.73 m2
  • Must not have active or latent TB on either chest radiograph or by Quantiferon gold test
  • 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.

You may not qualify if:

  • 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
  • Pure Class V membranous LN on a renal biopsy obtained within 12 weeks prior to signing ICF or during the screening period
  • Known intolerance to ≤1.0 gm/day of MMF
  • 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
  • Subjects, who at the time of signing the ICF, received any of the following immunosuppressive therapies after their qualifying biopsy
  • Oral corticosteroids \>0.5 mg/kg/day for more than 8 weeks or
  • Oral or IV pulse methylprednisolone \>3.0 gm (cumulative dose) or
  • IV cyclophosphamide \>2 pulses of high-dose (≥0.5 gm/m2) or \>4 doses of low dose (500 mg every 2 weeks) or
  • Average MMF \>2.5 gm/day (\>1800 mg/day of enteric-coated mycophenolate sodium) for more than 8 weeks or
  • Tacrolimus \>4 mg/day for more than 8 weeks
  • Major surgery within 8 weeks before signing the ICF or major surgery planned during the study period
  • 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
  • Confirmed positive test for hepatitis B or hepatitis C
  • Any severe herpes infection at any time prior to randomization
  • History of cancer, apart from:
  • +11 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (80)

Research Site

Glendale, Arizona, 85306, United States

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Research Site

Phoenix, Arizona, 85032, United States

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Research Site

La Jolla, California, 92037-0706, United States

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Los Angeles, California, 90095-1670, United States

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Thousand Oaks, California, 91360, United States

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Aurora, Colorado, 80045, United States

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DeBary, Florida, 32713, United States

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Boston, Massachusetts, 02118, United States

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Newark, New Jersey, 07103-2499, United States

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Great Neck, New York, 11021, United States

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New Hyde Park, New York, 11042, United States

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New York, New York, 10016, United States

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New York, New York, 10029, United States

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The Bronx, New York, 10457, United States

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Columbus, Ohio, 43210, United States

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Oklahoma City, Oklahoma, 73104, United States

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Memphis, Tennessee, 38119, United States

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Buenos Aires, C1015ABO, Argentina

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Córdoba, 5016, Argentina

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Rosario, S2000PBJ, Argentina

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Adelaide, 5000, Australia

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Clayton, VIC 3168, Australia

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Parkville, 3050, Australia

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Westmead, 2145, Australia

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Brussels, 1070, Belgium

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Brussels, 1200, Belgium

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Leuven, 3000, Belgium

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Liège, B-4000, Belgium

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Bordeaux, 33076, France

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Marseille, 13005, France

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Paris, 75013, France

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Strasbourg, 67098, France

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Toulouse, 31059, France

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Berlin, 10117, Germany

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Kiel, 24105, Germany

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Budapest, 1097, Hungary

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Debrecen, 4032, Hungary

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Kaposvár, 7400, Hungary

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Szeged, 6725, Hungary

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Milan, 20132, Italy

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Padua, 35128, Italy

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Pisa, 56126, Italy

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Reggio Emilia, 42100, Italy

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Chihuahua City, 31000, Mexico

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Guadalajara, 44160, Mexico

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Guadalajara, 44280, Mexico

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México, 14080, Mexico

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San Luis Potosí City, 78213, Mexico

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Arequipa, AREQUIPA54, Peru

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Lima, L14, Peru

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Lima, L34, Peru

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Lima, LIMA 01, Peru

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Lima, LIMA 31, Peru

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Lima, LIMA 32, Peru

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Lima, LIMA 33, Peru

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Lima, Lima-1, Peru

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Lima, Peru

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Krakow, 31-066, Poland

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Lodz, 92-213, Poland

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Warsaw, 02-637, Poland

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Orenburg, 460018, Russia

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Saint Petersburg, 197022, Russia

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Saint Petersburg, 197089, Russia

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Belgrade, 11000, Serbia

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Belgrade, 1100, Serbia

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Niš, 18000, Serbia

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Novi Sad, 21000, Serbia

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Gwangju, 501-757, South Korea

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Seoul, 05505, South Korea

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Seoul, 150-713, South Korea

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Suwon, 16499, South Korea

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Barcelona, 08035, Spain

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Barcelona, 08036, Spain

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Changhua, 50006, Taiwan

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Kaohsiung City, 80756, Taiwan

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Taichung, 40447, Taiwan

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Taichung, 40705, Taiwan

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Taipei, 100, Taiwan

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Taoyuan, 333, Taiwan

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London, E1 1BB, United Kingdom

Location

Related Publications (2)

  • 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.

  • 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.

Related Links

MeSH Terms

Conditions

Lupus NephritisNephritis

Interventions

anifrolumab

Condition Hierarchy (Ancestors)

GlomerulonephritisKidney DiseasesUrologic DiseasesFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesMale Urogenital DiseasesLupus Erythematosus, SystemicConnective Tissue DiseasesSkin and Connective Tissue DiseasesAutoimmune DiseasesImmune System Diseases

Results Point of Contact

Title
Global Clinical Lead
Organization
AstraZeneca Clinical study Information Center

Study Officials

  • AstraZeneca AB

    AstraZeneca

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

August 31, 2015

First Posted

September 14, 2015

Study Start

November 4, 2015

Primary Completion

November 26, 2019

Study Completion

January 18, 2021

Last Updated

November 24, 2021

Results First Posted

November 24, 2021

Record last verified: 2021-10

Data Sharing

IPD Sharing
Will share

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:

Shared Documents
STUDY PROTOCOL, SAP
Time Frame
AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles.
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.
More information

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