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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)

This study is currently recruiting participants.
Verified November 2017 by AstraZeneca
Sponsor:
ClinicalTrials.gov Identifier:
NCT02547922
First Posted: September 14, 2015
Last Update Posted: November 16, 2017
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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborator:
Parexel
Information provided by (Responsible Party):
AstraZeneca
  Purpose
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 Intervention Phase
Lupus Nephritis Biological: Anifrolumab Drug: Placebo Phase 2

Study Type: Interventional
Study Design: 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

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • Relative difference in change from baseline in 24-hour urine protein to creatinine ratio (UPCR) [ Time Frame: From Week 1 (baseline) to Week 52 ]

Secondary Outcome Measures:
  • 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)

  • Adverse Events [ Time Frame: Week 0-52 ]
    Including AEs of special interest [AESIs].


Estimated Enrollment: 150
Actual Study Start Date: November 4, 2015
Estimated Study Completion Date: July 20, 2020
Estimated Primary Completion Date: May 27, 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 administration every 4 week from Week 0 to Week 100 in addition to SOC which will continue until Week 112

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).
  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 70 Years   (Adult, Senior)
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 (b) Oral corticosteroids >0.5 mg/kg/day for more than 8 weeks or (c) Oral or IV pulse methylprednisolone >3.0 gm (cumulative dose) or (d) IV cyclophosphamide >2 pulses of high-dose (≥0.5 gm/m2) or >4 doses of low dose (500 mg every 2 weeks) or (e) Average MMF >2.5 gm/day (>1800 mg/day of enteric-coated mycophenolate sodium) for more than 8 weeks or (f) 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
  Contacts and Locations
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

  Show 122 Study Locations
Sponsors and Collaborators
AstraZeneca
Parexel
Investigators
Study Director: AstraZeneca AB AstraZeneca
  More Information

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT02547922     History of Changes
Other Study ID Numbers: D3461C00007
First Submitted: August 31, 2015
First Posted: September 14, 2015
Last Update Posted: November 16, 2017
Last Verified: November 2017
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
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs