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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)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02547922
Recruitment Status : Active, not recruiting
First Posted : September 14, 2015
Last Update Posted : April 14, 2020
Sponsor:
Collaborator:
Parexel
Information provided by (Responsible Party):
AstraZeneca

Tracking Information
First Submitted Date  ICMJE August 31, 2015
First Posted Date  ICMJE September 14, 2015
Last Update Posted Date April 14, 2020
Actual Study Start Date  ICMJE November 4, 2015
Actual Primary Completion Date November 26, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 5, 2018)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: September 10, 2015)
Relative difference in change from baseline in 24-hour urine protein to creatinine ratio (UPCR) [ Time Frame: From baseline (Week 1) to Week 52 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 5, 2018)
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: September 10, 2015)
  • 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
      • ≥80 mL/min/1.73 m2, if baseline eGFR was ≥90 mL/min/1.73 m2 or
      • >85% of baseline eGFR, if baseline eGFR was <90 mL/min/1.73 m2
    • 24-hour UPCR<0.5 mg/mg (please, note that the units are were changed from gm/gm to mg/mg, and will be updated in a future protocol amendment)
    • No discontinuation of investigational product or use of restricted medication beyond the protocol-allowed threshold before assessment
  • Difference in the proportion of subjects achieving the composite endpoint Alternative Complete Renal Response (aCRR) [ Time Frame: Week 52 ]
    aCRR is defined as meeting all of the following:
    • Estimated glomerular filtration rate (eGFR) is
      • ≥80 mL/min/1.73 m2, if baseline eGFR was ≥90 mL/min/1.73 m2 or
      • >85% of baseline eGFR, if baseline eGFR was <90 mL/min/1.73 m2
    • 24-hour UPCR<0.5 mg/mg (please, note that the units are were changed from gm/gm to mg/mg, and will be updated in a future protocol amendment)
    • No discontinuation of investigational product or use of restricted medication beyond the protocol allowed threshold before assessment
    • Inactive urine sediment (defined as <10 RBC/hpf)
  • Safety and tolerability: Adverse Events [ Time Frame: Week 0-52 ]
    Including adverse events of special interest [AESIs].
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety and Efficacy of Two Doses of Anifrolumab Compared to Placebo in Adult Subjects With Active Proliferative Lupus Nephritis
Official Title  ICMJE 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
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).
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  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Lupus Nephritis
Intervention  ICMJE
  • Biological: Anifrolumab
    Administration every 4 week from Week 0 to Week 100 in addition to SOC which will continue until Week 112
  • Drug: Placebo
    Administration every 4 week from Week 0 to Week 100 in addition to SOC which will continue until Week 112
Study Arms  ICMJE
  • Experimental: Anifrolumab - Lower Dose
    Anifrolumab - Lower Dose
    Intervention: Biological: Anifrolumab
  • Experimental: Anifrolumab - Higher Dose
    Anifrolumab - Higher Dose
    Intervention: Biological: Anifrolumab
  • Placebo Comparator: Placebo
    Placebo IV Q4W plus SOC
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: July 12, 2019)
146
Original Estimated Enrollment  ICMJE
 (submitted: September 10, 2015)
150
Estimated Study Completion Date  ICMJE January 22, 2021
Actual Primary Completion Date November 26, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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).
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Argentina,   Australia,   Belgium,   France,   Germany,   Hungary,   Italy,   Korea, Republic of,   Mexico,   Peru,   Poland,   Russian Federation,   Serbia,   Spain,   Taiwan,   United Kingdom,   United States
Removed Location Countries South Africa
 
Administrative Information
NCT Number  ICMJE NCT02547922
Other Study ID Numbers  ICMJE D3461C00007
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
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:
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (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.
URL: https://astrazenecagroup-dt.pharmacm.com/DT/Home
Responsible Party AstraZeneca
Study Sponsor  ICMJE AstraZeneca
Collaborators  ICMJE Parexel
Investigators  ICMJE
Study Director: AstraZeneca AB AstraZeneca
PRS Account AstraZeneca
Verification Date April 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP