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Safety and Efficacy of Two Doses of Anifrolumab Compared to Placebo in Adult Subjects With Active Proliferative Lupus Nephritis (TULIP-LN1)

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ClinicalTrials.gov Identifier: NCT02547922
Recruitment Status : Recruiting
First Posted : September 14, 2015
Last Update Posted : October 18, 2018
Sponsor:
Collaborator:
Parexel
Information provided by (Responsible Party):
AstraZeneca

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).

Condition or disease Intervention/treatment Phase
Lupus Nephritis Biological: Anifrolumab Drug: Placebo Phase 2

Detailed Description:
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).

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 150 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Multicentre, Randomised, Double-blind, Placebo-controlled, Phase 2 Study Evaluating the Efficacy and Safety of Anifrolumab in Adult Subjects With Active Proliferative Lupus Nephritis
Actual Study Start Date : November 4, 2015
Estimated Primary Completion Date : November 27, 2019
Estimated Study Completion Date : January 22, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Anifrolumab - Lower Dose
Anifrolumab - Lower Dose
Biological: Anifrolumab
Administration every 4 week from Week 0 to Week 100 in addition to SOC which will continue until Week 112

Experimental: Anifrolumab - Higher Dose
Anifrolumab - Higher Dose
Biological: Anifrolumab
Administration every 4 week from Week 0 to Week 100 in addition to SOC which will continue until Week 112

Placebo Comparator: Placebo
Placebo IV Q4W plus SOC
Drug: Placebo
Administration every 4 week from Week 0 to Week 100 in addition to SOC which will continue until Week 112




Primary Outcome Measures :
  1. Relative difference in change from baseline in 24-hour urine protein to creatinine ratio (UPCR) [ Time Frame: From Week 1 (baseline) up to Week 52 ]
    To evaluate the efficacy of anifrolumab plus SOC (combination of MMF and corticosteroids) compared with placebo plus SOC in subjects with active proliferative LN.


Secondary Outcome Measures :
  1. Difference in the proportion of subjects achieving the composite endpoint Complete Renal Response (CRR) [ Time Frame: Week 52 ]

    CRR is defined as meeting all of the following:

    • Estimated glomerular filtration rate (eGFR) is - ≥60 mL/min/1.73 m2 or no confirmed decrease of eGFR from baseline of ≥20%
    • 24-hour UPCR≤0.7 mg/mg
    • No discontinuation of investigational product (IP) or use of restricted medication beyond the protocol-allowed threshold before assessment.
    • eGFR is based on Modification of Diet in Renal Disease (MDRD) formula.

  2. No of subjects with adverse events (AEs) [ Time Frame: From baseline up to Week 52 ]
    To assess AEs (non-serious, serious and special interest) as variables of safety and tolerability of anifrolimab.

  3. Columbia-Suicide Severity Rating Scale (C-SSRS) [ Time Frame: From baseline up to Week 52 ]
    The C-SSRS will assess suicidal ideation and behavior on a graded scale from 1 to 5. 1 indicates as low suicidal and 5 as high suicidal behavior.

  4. Personal Health Questionnaire Depression Scale-8 [ Time Frame: At week 0, week 12, week 24, week 36, and week 52. ]
    The PHQ-8 consists of eight of the nine criteria on which the Diagnostic and Statistical Manual of Mental Disorders (DSM) -IV diagnosis of depressive disorders is based. It assesses symptoms of depression over the last 2 weeks.

  5. Extra-renal flares using Systemic Lupus Erythematosus (SLE) Disease Activity Index 2000 (SLEDAI 2K) based Flare Assessment Instrument [ Time Frame: From baseline up to week 52 ]
    Flare will be defined as any one criterion present in either the Mild/Moderate Flare and/or Severe Flare categories. New or worsened manifestation should only be reported for manifestations of SLE. The SLEDAI-2K score range is 0 to 105 points with 0 indicating inactive disease.

  6. Number of subjects with abnormal findings in vital signs [ Time Frame: From baseline up to Week 52 ]
    To assess any clinically significant abnormal vital signs findings as variable of safety and tolerability after administration of anifrolumab.

  7. Number of subjects with abnormal findings in laboratory evaluations [ Time Frame: From baseline up to Week 52 ]
    To assess any clinically significant abnormal laboratory tests findings as variable of safety and tolerability after administration of anifrolumab.



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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Main 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.

Main 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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02547922


Contacts
Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com

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Sponsors and Collaborators
AstraZeneca
Parexel
Investigators
Study Director: AstraZeneca AB AstraZeneca

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT02547922     History of Changes
Other Study ID Numbers: D3461C00007
First Posted: September 14, 2015    Key Record Dates
Last Update Posted: October 18, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by AstraZeneca:
lupus, nephritis, randomized, placebo, anifrolumab, safety, efficacy, adult

Additional relevant MeSH terms:
Nephritis
Lupus Nephritis
Kidney Diseases
Urologic Diseases
Glomerulonephritis
Lupus Erythematosus, Systemic
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases