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Subcutaneous Anifrolumab in Adult Patients With Systemic Lupus Erythematosus (Tulip SC)

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.
 
ClinicalTrials.gov Identifier: NCT04877691
Recruitment Status : Recruiting
First Posted : May 7, 2021
Last Update Posted : May 16, 2023
Sponsor:
Collaborator:
Iqvia Pty Ltd
Information provided by (Responsible Party):
AstraZeneca

Study Description
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Brief Summary:
The purpose of this study is evaluating the efficacy and safety of SC antifrolumab in adult patients with moderate -to-severe SLE despite receiving standard therapy

Condition or disease Intervention/treatment Phase
Systemic Lupus Erythematosus Drug: Medi-546 Drug: Placebo Phase 3

Detailed Description:

This is a Phase 3, multicentre, multinational, randomised, double-blind, placebo-controlled study to evaluate the efficacy and safety of a subcutaneous treatment regimen of anifrolumab versus placebo in participants with moderately to severely active, autoantibody-positive systemic lupus erythematosus (SLE) while receiving standard of care (SOC) treatment. Participants must be taking either 1 or any combination of the following: oral glucocorticoids, antimalarial, and/or immunosuppressants. The study will be performed in adult participants of 18 to 70 years of age.

Approximately 360 participants receiving SOC treatment will be randomised in a 1:1 ratio to receive a fixed subcutaneous dose of anifrolumab or placebo administered once weekly via an accessorized prefilled syringe and with the primary endpoint evaluated at Week 52.

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 360 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Masking Description: Double Blind (Participant, Care Provider and Investigator)
Primary Purpose: Treatment
Official Title: A Multicenter, Randomized, Double-Blind, Placebo-controlled, Phase 3 Study Evaluating the Efficacy and Safety of Subcutaneous Anifrolumab in Adult Patients With Systemic Lupus Erythematosus
Actual Study Start Date : June 8, 2021
Estimated Primary Completion Date : August 28, 2024
Estimated Study Completion Date : August 22, 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lupus
Drug Information available for: Anifrolumab

Arms and Interventions
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Arm Intervention/treatment
Experimental: Anifrolumab
Solution for injection in aPFS
 Drug: Medi-546

Patients will have IP administered or will self-administer IP under supervision by site staff at Weeks 0, 1, and 2. For weekly doses coinciding with subsequent on-site visits, patients will also have IP administered or will self-administer IP under supervision by site staff, and in addition will receive a set of kits (including back-up kits) for at-home administration, as follows:

  • - W0 and W1 - 1 kit to be administered at clinic
  • - W2 - 3 kits (1 to be administered at clinic, 2 to be taken home)
  • - W4 - W48 (every 4 weeks) - 5 kits (1 to be administered at clinic, 4 to be taken home) Patients will have approximately 65 kits (including back-up kits) dispensed to them over the course of the 52-week treatment period
Placebo Comparator: Placebo
Solution for injection in aPFS
 Drug: Placebo
Solution for injection in aPFS


Outcome Measures
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Primary Outcome Measures :
  1. British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) response [ Time Frame: At week 52 ]

    The primary endpoint is response in BICLA, a composite binary endpoint whereby responders are defined by meeting all of the following criteria:

    • Improvement from baseline in disease activity as measured by BILAG-2004. Improvement is defined as a reduction of all baseline BILAG-2004 A to B/C/D and baseline BILAG-2004 B to C/D and no BILAG-2004 worsening in other organ systems, where worsening is defined as ≥ 1 new BILAG-2004 A or ≥ 2 new BILAG 2004 B.
    • No worsening from baseline in SLEDAI-2K, where worsening is defined as an increase from baseline of > 0 points in SLEDAI-2K.
    • No worsening from baseline in the patient's lupus disease activity, where worsening is defined as an increase ≥ 0.30 points on a 3-point PGA VAS.
    • No discontinuation of investigational product.
    • No use of restricted medications beyond the protocol-allowed threshold.


Secondary Outcome Measures :
  1. Time to first BICLA response sustained through Week 52 [ Time Frame: Baseline through to Week 52 ]
    Time from first dose to first BICLA response that is consecutively maintained through Week 52

  2. BICLA response with maintained low (or reduced) use of oral corticosteroid (OCS) [ Time Frame: At week 52 ]

    Response is defined by being a BICLA responder at Week 52 and having maintained low (or reduced) OCS use through Week 52. Maintained OCS use is defined as follows:

    • If baseline OCS ≥ 10 mg/day an OCS dose of ≤ 7.5 mg/day prednisone or equivalent must be achieved by Week 40 and an OCS dose ≤ 7.5 mg/day prednisone or equivalent must be maintained from Week 40 to Week 52.
    • If baseline OCS < 10 mg/day, OCS dose at Week 40 must be less than or equal to OCS dose at baseline, with no increase from Week 40 OCS dose between Week 40 and Week 52.

  3. BICLA response [ Time Frame: At week 16 ]
    Same definition as primary outcome measure.

  4. Time to flare [ Time Frame: Baseline through to Week 52 ]
    Flare defined as either 1 or more BILAG 2004 A or 2 or more BILAG 2004 B compared to previous visit

  5. ≥ 50% reduction in Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) activity score in the sub-group of patients with baseline CLASI activity score ≥ 10 [ Time Frame: At week 12 ]
  6. Maintained oral corticosteroid (OCS) reduction among patients with baseline OCS ≥10 mg/day. [ Time Frame: At week 52 ]

    Achieving maintained OCS reduction through Week 52 is defined by meeting all of the following criteria:

    • Achieve an OCS dose of ≤ 7.5 mg/day prednisone or equivalent by Week 40
    • Maintain an OCS dose ≤ 7.5 mg/day prednisone or equivalent from Week 40 to Week 52
    • No discontinuation of investigational product
    • No use of restricted medications beyond the protocol allowed threshold before assessment

  7. Change in the number of swollen and tender joints compared to baseline among patients with ≥ 6 swollen and ≥ 6 tender joints at baseline. [ Time Frame: At week 52 ]

    Achieving a change in number of swollen and tender joints is defined by meeting all of the following criteria:

    • ≥ 50% change in the number of swollen and ≥ 50% change in the number of tender joints
    • No discontinuation of IP
    • No use of restricted medications beyond the protocol allowed threshold before assessment

  8. Annualized flare rate [ Time Frame: Baseline through to Week 52 ]
    Flare defined as either 1 or more BILAG 2004 or 2 or more BILAG2004 B compared to previous visit

  9. Systemic Lupus Erythematosus Responder Index of ≥ 4 (SRI[4]) response [ Time Frame: At week 52 ]

    Response is defined by meeting all of the following criteria:

    • Reduction from baseline of ≥ 4 points in the SLEDAI-2K
    • No new organ systems affected as defined by 1 or more BILAG-2004 A or 2 or more BILAG 2004 B items compared to baseline using BILAG-2004
    • No worsening from baseline in the patients' lupus disease activity, where worsening is defined by an increase ≥ 0.30 points on a 3 point PGA VAS
    • No discontinuation of IP
    • No use of restricted medications beyond the protocol allowed threshold before assessment

  10. Chronic Illness Therapy-FATIGUE (FACIT-F) score [ Time Frame: At week 52 ]

Other Outcome Measures:
  1. Adverse Event Overview [ Time Frame: Baseline through Week 60 ]
    Overview of AEs, SAEs and AESIs


Eligibility Criteria
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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.


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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

Inclusion Criteria:

Inclusion CriteriaErythematosus

  1. Patients who have a diagnosis of pediatric or adult SLE according to the ACR 1997 revised criteria for ≥ 24 weeks prior to signing the ICF
  2. To be eligible a patient must have SLEDAI-2K ≥ 6 points and "Clinical" SLEDAI-2K score ≥4 points at screening

  3. BILAG2004 with at least 1 of the following:

    1. BILAG2004 level A disease in ≥ 1 organ system
    2. BILAG2004 level B disease in ≥ 2 organ systems
  4. Physician's Global Assessment (PGA) score ≥ 1.0 on a 0 to 3 VAS at Screening
  5. Antinuclear antibody, and/or Anti-dsDNA and/oranti-Smith positive at Screening,

  6. Must be on stable background standard therapy with DMARD, glucocorticoids or anti-malarials alone or in combinations.

    Exclusion Criteria:

  7. Active severe or unstable neuropsychiatric SLE
  8. Active severe SLE-driven renal disease
  9. 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.
  10. History of recurrent infection requiring hospitalization and IV antibiotics (eg, 3 or more of the same type of infection over the previous 52 weeks).
  11. Known history of a primary immunodeficiency, splenectomy, or any underlying condition that predisposes the patient to infection, or a positive result for human immunodeficiency virus (HIV) infection confirmed by central laboratory at Screening.
  12. At Screening, confirmed positive test for hepatitis B serology and positive test for hepatitis C antibody
  13. Any severe case herpes zoster infection at any time prior to Week 0 (Day 1),
  14. Opportunistic infection requiring hospitalization or IV antimicrobial treatment within 3 years of randomization.

  15. History of cancer, apart from:

    1. Squamous or basal cell carcinoma of the skin treated with documented success of curative therapy ≥ 3 months prior to Week 0 (Day 1)
    2. Cervical cancer in situ treated with apparent success with curative therapy ≥ 1 year prior to Week 0 (Day 1).
Contacts and Locations
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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): NCT04877691


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

Locations
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Sponsors and Collaborators
AstraZeneca
Iqvia Pty Ltd
More Information
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Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT04877691    
Other Study ID Numbers: D3465C00001
SZA64400
2020-004529-22 ( EudraCT Number )
First Posted: May 7, 2021    Key Record Dates
Last Update Posted: May 16, 2023
Last Verified: May 2023
Individual Participant Data (IPD) Sharing Statement:
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: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Supporting Materials: Study Protocol
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. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
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. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
URL: https://astrazenecagroup-dt.pharmacm.com/DT/Home

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by AstraZeneca:
Systemic Lupus Erythematosuss Anifrolumab, Adult patients, BICLA, glucocorticoids, Immunosuppressant(s), sub-cutaneous
Additional relevant MeSH terms:
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Lupus Erythematosus, Systemic
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases