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A Study to Investigate the Efficacy and Safety of Anifrolumab in Adults With Chronic and/or Subacute Cutaneous Lupus Erythematosus (LAVENDER)

Primary Purpose

Cutaneous Lupus Erythematosus

Status
Not yet recruiting
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Anifrolumab
Placebo
Sponsored by
AstraZeneca
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cutaneous Lupus Erythematosus focused on measuring Lupus erythematosus, Cutaneous lupus erythematosus, anifrolumab, Cutaneous Lupus Erythematosus Disease Area Severity Index, Cutaneous Lupus Erythematosus Disease Area Severity Index responder index 7

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Participants are eligible to be included in the study only if all of the following criteria apply: Participants must have a confirmed diagnosis of CLE. Diagnosis must be clinically and histologically confirmed with the following: CLASI-A total score ≥ 10 points at Screening and confirmed at randomization. Combined CLASI-A score for Erythema and Scale/Hypertrophy components ≥ 7 points. They should have experienced inadequate response or be intolerant to anti-malarial therapy. In case an anti-malarial treatment was never given, they should have tried one of the following medications for CLE: topical calcineurin inhibitors, systemic glucocorticoids, or a conventional immunosuppressant. Participants should have no medical history or signs or symptoms of active or prior tuberculosis infection (TB) and the same should reflect in chest radiograph or a chest CT scan result. No history of latent TB prior to initial Screening Visit. The participant must undergo an IFN-γ release assay IGRA (e.g., QFT-G test) test for TB. Contraceptive use by males and females should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. Females who have been or are sexually active with an intact cervix must have documentation of a cervical cancer screening as per local guidelines (Pap smear or HPV tests). Participants should have a COVID-19 negative PCR or antigen test result as per local policies at Screening. They should also not have had known or suspected COVID-19 exposure within 2 weeks prior to screening based on the COVID-19 questionnaire. If there is a known or suspected exposure, a participant must be negative upon retest obtained after 2 weeks and must remain asymptomatic for inclusion in the study. Exclusion criteria: Participants are excluded from the study if any of the following criteria apply: History or evidence of suicidal ideation. Severe or life-threatening SLE. Active SLE or Sjögren's Syndrome. Any active skin conditions other than CLE that may interfere with the study. History of recurrent infection requiring hospitalization and IV antibiotics. Known history of primary immunodeficiency, splenectomy, or any underlying condition that makes the participant prone to infection, or a positive result for HIV infection at Screening. Confirmed positive test for hepatitis B serology at screening. Presence of active hepatitis C infection. Any severe case, as defined by study guidelines, of herpes zoster infection. Any clinical cytomegalovirus (CMV) or Epstein-Barr virus infection that has not completely resolved. Any severe case, as defined by study guidelines, of herpes zoster infection at any time prior to randomization (Day 1). Any herpes zoster infection that has not completely resolved within 12 weeks prior to signing the informed consent form (ICF). Any clinical CMV or Epstein Barr virus infection that has not completely resolved within 12 weeks prior to signing the ICF. Clinically significant chronic infection within 8 weeks prior to signing the ICF or any infection requiring hospitalization or treatment with IV anti-infectives not completed at least 4 weeks prior to signing the ICF. COVID-19 infection History of severe COVID-19 infection or any prior COVID-19 infection with documented long COVID-19 and/or clinically significant unresolved complications due to COVID-19 infection. Mild/asymptomatic COVID-19 infection within the last 6 weeks prior to first dosing. Confirmed or probable COVID-19 infection based on clinical symptoms and radiologic imaging within 3 months prior to Day 1. COVID-19 vaccine received within 30 days of randomization (Day 1). Participants who do not meet the study restrictions for using all biologics including anifrolumab, B- cell depleting therapies (eg, rituximab), and investigational product for CLE. A known history of allergy or reaction to any component of the study intervention formulation or history of anaphylaxis to any human gamma globulin therapy. Any history of an anaphylactic reaction to human proteins, or monoclonal antibodies. At screening, if participants do not meet the eligibility criteria assessed based on laboratory test results e.g tests for total bilirubin, serum creatinine etc.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Placebo Comparator

    Arm Label

    Anifrolumab

    Placebo

    Arm Description

    The participants will receive dose A of anifrolumab as a SC injection from Week 0/Day 1 upto and including week 51.

    The participant will receive placebo as a SC injection from Week 0/Day 1 to Week 23. From Week 24 the participants will receive dose A of anifrolumab up to and including Week 51.

    Outcomes

    Primary Outcome Measures

    Number of participants with Cutaneous Lupus Erythematosus Disease Area and Severity Index - Activity (CLASI-A) CLASI-A Responder Index-7 (CRI- 7) response (United States)
    CLASI is index for assessing cutaneous lesions of systemic lupus erythematosus (SLE). It consists of 2 scores: i) activity of disease, and ii) measure of damage. Activity score considers factors as erythema, scale/hypertrophy, mucous membrane lesions, recent hair loss and non-scarring alopecia. Damage score represents dyspigmentation, scarring/atrophy/panniculitis, and scarring of scalp. A 7-point reduction CLASI-A is established as clinically meaningful improvement in disease for CLE and as being impactful for patients. CLASI-A score is indicative of severity of skin manifestations of CLE, and achieving a CLASI-A total score of 9 or below is an accepted threshold for mild disease. At Week 24, CLASI-A Responder Index-7 (CRI-7) response will be assessed, and a responder (yes/no) is a participant who meets all following criteria: • ≥ 7-point reduction from baseline in CLASI-A score. • Total CLASI-A score at Week 24 of ≤ 9. A participant who does not meet these criteria is non-responder.
    Number of participants with CLASI-70 response (European Union and Rest of the World)
    The CLASI is a validated index used for assessing the cutaneous lesions of SLE. The CLASI instrument will be used at each study visit to capture individual skin manifestation scores. CLASI-70 responder (Yes/No) is defined as a participant who achieves a 70% reduction relative to baseline in CLASI-A score. Otherwise, the participant is considered a non-responder.

    Secondary Outcome Measures

    Percent change from baseline in total erythema score (United States, European Union and Rest of the World)
    The CLASI is a validated index used for assessing the cutaneous lesions of SLE. The CLASI instrument will be used at each study visit to capture individual skin manifestation scores. Assessment of CLASI-A erythema score captures changes in erythema, a clinically important feature in CLE patients. A CLASI-A erythema score of 0 is absent, 1 is pink faint erythema, 2 is red, 3 is dark red; purple/violaceous/crusted/hemorrhagic. Assessment of CLASI-A erythema score captures changes in erythema, a clinically important feature in CLE patients.
    Percent change from baseline in total scale/hypertrophy score (United States, European Union and Rest of the World)
    Assessment of CLASI-A scale/hypertrophy score captures extent of hypertrophy, a clinically important feature in CLE patients. The CLASI is a validated index used for assessing the cutaneous lesions of SLE. CLASI-A Scale/Hypertrophy can be measured as 0, 1, and 2 where 0 is absent, 1 is scale, and 2 is verrucuos and hypertrohic.
    Number of participants with CLASI-A Responder Index-7 (CRI-7) response (United States)
    The CLASI is a validated index used for assessing the cutaneous lesions of SLE. The CLASI instrument will be used at each study visit to capture individual skin manifestation scores. A 7-point reduction CLASI-A is established as clinically meaningful improvement in disease for CLE and as being impactful for patients. Achieving a CLASI-A total score of 9 or below is an accepted threshold for mild disease. At Week 12, CLASI-A Responder Index-7 (CRI-7) response will be assessed, and a responder (yes/no) is defined as a participant who meets all the following criteria: ≥ 7-point reduction from baseline in CLASI-A score. Total CLASI-A score of ≤ 9. A participant who does not meet these criteria is a non-responder.
    Number of participants with CLASI-70 response (European Union and Rest of the World)
    The CLASI is a validated index used for assessing the cutaneous lesions of SLE. CLASI-70 responder is defined as a participant who achieves a 70% reduction relative to baseline in CLASI-A score. Otherwise, the participant is considered a non-responder.
    Number of participants with Cutaneous Lupus Activity of Physician's Global Assessment-Revised (CLA-IGA-R) erythema score of 0 or 1 (United States)
    The CLA-IGA-R is an assessment tool that scores the three key disease components (erythema; OMC [other morphological characteristics] and follicular activity) of CLE independently. The CLA-IGA-R erythema is scored on a five-point binary scale that provides a global clinical assessment ranging from 0 to 4, where 0 indicates clear, 1 is almost clear, 2 is mild, 3 is moderate, and 4 indicates severe CLE. On all IGA scales, a decrease in score relates to an improvement in signs and symptoms. Assessment of CLA-IGA-R erythema score captures changes in erythema, a clinically important feature in CLE patients. A decrease in score relates to an improvement in signs and symptoms.
    Number of participants with Cutaneous Lupus Activity of Physician's Global Assessment-Revised (CLA-IGA-R) other morphological characteristics (OMC) score of 0 (United States)
    The CLA-IGA-R is an assessment tool that scores the three key disease components (erythema; OMC and follicular activity) of CLE independently. The CLA-IGA-R OMC is scored on a five-point binary scale that provides a global clinical assessment ranging from 0 to 4, where 0 indicates clear, 1 is almost clear, 2 is mild, 3 is moderate, and 4 indicates severe CLE. Assessment of CLA-IGA-R OMC score captures other morphological changes in CLE patients. A decrease in score relates to an improvement in signs and symptoms.
    Number of participants with ≥ 7-point reduction from baseline in CLASI-A total score (United States)
    The CLASI is a validated index used for assessing the cutaneous lesions of SLE. It consists of 2 separate scores: i) activity of the disease, and ii) measure of damage. The CLASI instrument will be used at each study visit to capture individual skin manifestation scores. A 7-point reduction CLASI-A is established as clinically meaningful improvement in disease for CLE and as being impactful for patients. Achieving a CLASI-A total score of 9 or below is an accepted threshold for mild disease.
    Number of participants with a total CLASI-A total score of ≤ 9 (United States)
    The CLASI is a validated index used for assessing the cutaneous lesions of SLE. The CLASI instrument will be used at each study visit to capture individual skin manifestation scores. It consists of 2 separate scores: i) activity of the disease, and ii) measure of damage. A 7-point reduction CLASI-A is established as clinically meaningful improvement in disease for CLE and as being impactful for participants. Achieving a CLASI-A total score of 9 or below is an accepted threshold for mild disease.
    Number of participants with CLA-IGA-R OMC score of 0 or 1 (United States)
    The CLA-IGA-R is an assessment tool that scores the three key disease components (erythema; OMC and follicular activity) of CLE independently. The CLA-IGA-R OMC is scored on a five-point binary scale that provides a global clinical assessment ranging from 0 to 4, where 0 indicates clear, 1 is almost clear, 2 is mild, 3 is moderate, and 4 indicates severe CLE. Assessment of CLA-IGA OMC score captures other morphological changes in CLE patients. A decrease in score relates to an improvement in signs and symptoms.
    Number of participants with CLA-IGA-R follicular activity score of 0 (United States)
    The CLA-IGA-R is an assessment tool that scores the three key disease components (erythema; OMC and follicular activity) of CLE independently. CLA-IGA-R follicular activity provides a global clinical assessment on a 2-point binary scale ranging from 0 to 1, where 0 indicates absent and 1 indicates present. A decrease in score relates to an improvement in signs and symptoms.
    Change from baseline in Skindex-29+3 domain scores (United States, European Union and Rest of the World)
    The Skindex-29+3 is based on a previous instrument, the Skindex-29 and has been modified to include items related to CLE. The instrument consists of 33 items, which are used to calculate 4 domains: Symptoms (7 items), emotions (10 items), Functioning (12 items), and Lupus-specific (3 items). The remaining item asks the participants to rate how often they worry about side effects from treatment; however, this item is not used to calculate the domain scores. The response options are on a 5-point verbal rating scale, ranging from 1 (Never) to 5 (All the time). The instrument has a recall period of the previous 4 weeks. Each domain score ranges from 0 to 100 points, with higher scores indicating worse health-related quality of life. The symptom domain in the Skindex-29+3 evaluates the symptom burden of the disease and includes symptom concepts such as pain, itching, burning, stinging, and sensitivity.
    Number of participants with CLASI-70 responders upto Week 52 (European Union and Rest of the World)
    The CLASI is a validated index used for assessing the cutaneous lesions of SLE. CLASI-70 responder is defined as a participant who achieves a 70% reduction relative to baseline in CLASI-A score. Otherwise, the participant is considered a non-responder. Amongst participants randomized to anifrolumab during the double-blind treatment period, the number of participants who maintained a CLASI-70 response from Week 24 upto Week 52 will be evaluated.
    Serum trough (pre-dose) concentrations of anifrolumab
    The Ctrough of subcutaneously administered anifrolumab in participants with chronic and/or subacute CLE will be evaluated.
    Number of participants with positive antidrug antibody
    The immunogenicity of subcutaneously administered anifrolumab in participants with chronic and/or subacute CLE will be evaluated.
    Percent change from baseline in suppression of the interferon 21 gene
    The pharmacodynamic of subcutaneously administered anifrolumab in participants with chronic and/or subacute CLE will be evaluated.

    Full Information

    First Posted
    August 1, 2023
    Last Updated
    September 21, 2023
    Sponsor
    AstraZeneca
    Collaborators
    Parexel
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    1. Study Identification

    Unique Protocol Identification Number
    NCT06015737
    Brief Title
    A Study to Investigate the Efficacy and Safety of Anifrolumab in Adults With Chronic and/or Subacute Cutaneous Lupus Erythematosus
    Acronym
    LAVENDER
    Official Title
    A Multicenter, Randomized, Double Blind, Placebo Controlled, Phase III Study to Evaluate the Efficacy and Safety of Anifrolumab in Adults With Chronic and/or Subacute Cutaneous Lupus Erythematosus Who Are Refractory and/or Intolerant to Antimalarial Therapy
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    September 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    October 25, 2023 (Anticipated)
    Primary Completion Date
    March 25, 2026 (Anticipated)
    Study Completion Date
    December 16, 2026 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    AstraZeneca
    Collaborators
    Parexel

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    Yes
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    This study aims to evaluate the efficacy and safety of a subcutaneous (SC) treatment regimen of dose A of anifrolumab versus placebo in adult participants with cutaneous lupus erythematosus (CLE).
    Detailed Description
    The study will have a randomized, double-blind, placebo-controlled design, followed by an open-label treatment period. The study will include: Screening Period (within 6-weeks [42 days] prior to randomization). Double-blinded Treatment Period (24 weeks) Open-label Treatment Period (28 weeks) Safety Follow-up Period (12 weeks) Eligible participants will be randomized in a 1:1 ratio to receive either dose A of anifrolumab or placebo through SC route. The study duration for a participant will be a maximum of 71 weeks.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Cutaneous Lupus Erythematosus
    Keywords
    Lupus erythematosus, Cutaneous lupus erythematosus, anifrolumab, Cutaneous Lupus Erythematosus Disease Area Severity Index, Cutaneous Lupus Erythematosus Disease Area Severity Index responder index 7

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 3
    Interventional Study Model
    Parallel Assignment
    Model Description
    This is a parallel group treatment study with two arms.
    Masking
    ParticipantInvestigator
    Allocation
    Randomized
    Enrollment
    230 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Anifrolumab
    Arm Type
    Experimental
    Arm Description
    The participants will receive dose A of anifrolumab as a SC injection from Week 0/Day 1 upto and including week 51.
    Arm Title
    Placebo
    Arm Type
    Placebo Comparator
    Arm Description
    The participant will receive placebo as a SC injection from Week 0/Day 1 to Week 23. From Week 24 the participants will receive dose A of anifrolumab up to and including Week 51.
    Intervention Type
    Combination Product
    Intervention Name(s)
    Anifrolumab
    Intervention Description
    Anifrolumab will be provided as a solution for injection in accessorized pre-filled syringe (aPFS).
    Intervention Type
    Other
    Intervention Name(s)
    Placebo
    Intervention Description
    Matching placebo solution for injection in aPFS.
    Primary Outcome Measure Information:
    Title
    Number of participants with Cutaneous Lupus Erythematosus Disease Area and Severity Index - Activity (CLASI-A) CLASI-A Responder Index-7 (CRI- 7) response (United States)
    Description
    CLASI is index for assessing cutaneous lesions of systemic lupus erythematosus (SLE). It consists of 2 scores: i) activity of disease, and ii) measure of damage. Activity score considers factors as erythema, scale/hypertrophy, mucous membrane lesions, recent hair loss and non-scarring alopecia. Damage score represents dyspigmentation, scarring/atrophy/panniculitis, and scarring of scalp. A 7-point reduction CLASI-A is established as clinically meaningful improvement in disease for CLE and as being impactful for patients. CLASI-A score is indicative of severity of skin manifestations of CLE, and achieving a CLASI-A total score of 9 or below is an accepted threshold for mild disease. At Week 24, CLASI-A Responder Index-7 (CRI-7) response will be assessed, and a responder (yes/no) is a participant who meets all following criteria: • ≥ 7-point reduction from baseline in CLASI-A score. • Total CLASI-A score at Week 24 of ≤ 9. A participant who does not meet these criteria is non-responder.
    Time Frame
    At Week 24
    Title
    Number of participants with CLASI-70 response (European Union and Rest of the World)
    Description
    The CLASI is a validated index used for assessing the cutaneous lesions of SLE. The CLASI instrument will be used at each study visit to capture individual skin manifestation scores. CLASI-70 responder (Yes/No) is defined as a participant who achieves a 70% reduction relative to baseline in CLASI-A score. Otherwise, the participant is considered a non-responder.
    Time Frame
    At Week 24
    Secondary Outcome Measure Information:
    Title
    Percent change from baseline in total erythema score (United States, European Union and Rest of the World)
    Description
    The CLASI is a validated index used for assessing the cutaneous lesions of SLE. The CLASI instrument will be used at each study visit to capture individual skin manifestation scores. Assessment of CLASI-A erythema score captures changes in erythema, a clinically important feature in CLE patients. A CLASI-A erythema score of 0 is absent, 1 is pink faint erythema, 2 is red, 3 is dark red; purple/violaceous/crusted/hemorrhagic. Assessment of CLASI-A erythema score captures changes in erythema, a clinically important feature in CLE patients.
    Time Frame
    At Week 24
    Title
    Percent change from baseline in total scale/hypertrophy score (United States, European Union and Rest of the World)
    Description
    Assessment of CLASI-A scale/hypertrophy score captures extent of hypertrophy, a clinically important feature in CLE patients. The CLASI is a validated index used for assessing the cutaneous lesions of SLE. CLASI-A Scale/Hypertrophy can be measured as 0, 1, and 2 where 0 is absent, 1 is scale, and 2 is verrucuos and hypertrohic.
    Time Frame
    At Week 24
    Title
    Number of participants with CLASI-A Responder Index-7 (CRI-7) response (United States)
    Description
    The CLASI is a validated index used for assessing the cutaneous lesions of SLE. The CLASI instrument will be used at each study visit to capture individual skin manifestation scores. A 7-point reduction CLASI-A is established as clinically meaningful improvement in disease for CLE and as being impactful for patients. Achieving a CLASI-A total score of 9 or below is an accepted threshold for mild disease. At Week 12, CLASI-A Responder Index-7 (CRI-7) response will be assessed, and a responder (yes/no) is defined as a participant who meets all the following criteria: ≥ 7-point reduction from baseline in CLASI-A score. Total CLASI-A score of ≤ 9. A participant who does not meet these criteria is a non-responder.
    Time Frame
    At Week 12
    Title
    Number of participants with CLASI-70 response (European Union and Rest of the World)
    Description
    The CLASI is a validated index used for assessing the cutaneous lesions of SLE. CLASI-70 responder is defined as a participant who achieves a 70% reduction relative to baseline in CLASI-A score. Otherwise, the participant is considered a non-responder.
    Time Frame
    At Week 12
    Title
    Number of participants with Cutaneous Lupus Activity of Physician's Global Assessment-Revised (CLA-IGA-R) erythema score of 0 or 1 (United States)
    Description
    The CLA-IGA-R is an assessment tool that scores the three key disease components (erythema; OMC [other morphological characteristics] and follicular activity) of CLE independently. The CLA-IGA-R erythema is scored on a five-point binary scale that provides a global clinical assessment ranging from 0 to 4, where 0 indicates clear, 1 is almost clear, 2 is mild, 3 is moderate, and 4 indicates severe CLE. On all IGA scales, a decrease in score relates to an improvement in signs and symptoms. Assessment of CLA-IGA-R erythema score captures changes in erythema, a clinically important feature in CLE patients. A decrease in score relates to an improvement in signs and symptoms.
    Time Frame
    At Week 24
    Title
    Number of participants with Cutaneous Lupus Activity of Physician's Global Assessment-Revised (CLA-IGA-R) other morphological characteristics (OMC) score of 0 (United States)
    Description
    The CLA-IGA-R is an assessment tool that scores the three key disease components (erythema; OMC and follicular activity) of CLE independently. The CLA-IGA-R OMC is scored on a five-point binary scale that provides a global clinical assessment ranging from 0 to 4, where 0 indicates clear, 1 is almost clear, 2 is mild, 3 is moderate, and 4 indicates severe CLE. Assessment of CLA-IGA-R OMC score captures other morphological changes in CLE patients. A decrease in score relates to an improvement in signs and symptoms.
    Time Frame
    At Week 24
    Title
    Number of participants with ≥ 7-point reduction from baseline in CLASI-A total score (United States)
    Description
    The CLASI is a validated index used for assessing the cutaneous lesions of SLE. It consists of 2 separate scores: i) activity of the disease, and ii) measure of damage. The CLASI instrument will be used at each study visit to capture individual skin manifestation scores. A 7-point reduction CLASI-A is established as clinically meaningful improvement in disease for CLE and as being impactful for patients. Achieving a CLASI-A total score of 9 or below is an accepted threshold for mild disease.
    Time Frame
    At Week 24
    Title
    Number of participants with a total CLASI-A total score of ≤ 9 (United States)
    Description
    The CLASI is a validated index used for assessing the cutaneous lesions of SLE. The CLASI instrument will be used at each study visit to capture individual skin manifestation scores. It consists of 2 separate scores: i) activity of the disease, and ii) measure of damage. A 7-point reduction CLASI-A is established as clinically meaningful improvement in disease for CLE and as being impactful for participants. Achieving a CLASI-A total score of 9 or below is an accepted threshold for mild disease.
    Time Frame
    At Week 24
    Title
    Number of participants with CLA-IGA-R OMC score of 0 or 1 (United States)
    Description
    The CLA-IGA-R is an assessment tool that scores the three key disease components (erythema; OMC and follicular activity) of CLE independently. The CLA-IGA-R OMC is scored on a five-point binary scale that provides a global clinical assessment ranging from 0 to 4, where 0 indicates clear, 1 is almost clear, 2 is mild, 3 is moderate, and 4 indicates severe CLE. Assessment of CLA-IGA OMC score captures other morphological changes in CLE patients. A decrease in score relates to an improvement in signs and symptoms.
    Time Frame
    At Week 24
    Title
    Number of participants with CLA-IGA-R follicular activity score of 0 (United States)
    Description
    The CLA-IGA-R is an assessment tool that scores the three key disease components (erythema; OMC and follicular activity) of CLE independently. CLA-IGA-R follicular activity provides a global clinical assessment on a 2-point binary scale ranging from 0 to 1, where 0 indicates absent and 1 indicates present. A decrease in score relates to an improvement in signs and symptoms.
    Time Frame
    At Week 24
    Title
    Change from baseline in Skindex-29+3 domain scores (United States, European Union and Rest of the World)
    Description
    The Skindex-29+3 is based on a previous instrument, the Skindex-29 and has been modified to include items related to CLE. The instrument consists of 33 items, which are used to calculate 4 domains: Symptoms (7 items), emotions (10 items), Functioning (12 items), and Lupus-specific (3 items). The remaining item asks the participants to rate how often they worry about side effects from treatment; however, this item is not used to calculate the domain scores. The response options are on a 5-point verbal rating scale, ranging from 1 (Never) to 5 (All the time). The instrument has a recall period of the previous 4 weeks. Each domain score ranges from 0 to 100 points, with higher scores indicating worse health-related quality of life. The symptom domain in the Skindex-29+3 evaluates the symptom burden of the disease and includes symptom concepts such as pain, itching, burning, stinging, and sensitivity.
    Time Frame
    At Week 24
    Title
    Number of participants with CLASI-70 responders upto Week 52 (European Union and Rest of the World)
    Description
    The CLASI is a validated index used for assessing the cutaneous lesions of SLE. CLASI-70 responder is defined as a participant who achieves a 70% reduction relative to baseline in CLASI-A score. Otherwise, the participant is considered a non-responder. Amongst participants randomized to anifrolumab during the double-blind treatment period, the number of participants who maintained a CLASI-70 response from Week 24 upto Week 52 will be evaluated.
    Time Frame
    Upto Week 52
    Title
    Serum trough (pre-dose) concentrations of anifrolumab
    Description
    The Ctrough of subcutaneously administered anifrolumab in participants with chronic and/or subacute CLE will be evaluated.
    Time Frame
    Double-blind: Pre-dose on Day 1 (Week 0), Weeks 1, 4, 12, 24; Open-label: Weeks 40, and 52 or early discontinuation visit [EVD] and follow-up visit (13 Weeks after last dose)
    Title
    Number of participants with positive antidrug antibody
    Description
    The immunogenicity of subcutaneously administered anifrolumab in participants with chronic and/or subacute CLE will be evaluated.
    Time Frame
    Double-blind: Pre-dose on Day 1 (Week 0), Weeks 12, and 24; Open-label: Pre-dose on Weeks 40, and 52 or EVD and follow-up visit (13 weeks after last dose)
    Title
    Percent change from baseline in suppression of the interferon 21 gene
    Description
    The pharmacodynamic of subcutaneously administered anifrolumab in participants with chronic and/or subacute CLE will be evaluated.
    Time Frame
    Double-blind: Day 1 (Week 0), Week 4, Weeks 12, and 24; Open-label: Week 40, and 52 or EVD and follow-up visit (13 weeks after last dose)
    Other Pre-specified Outcome Measures:
    Title
    Number of participants with adverse events (United States, European Union and Rest of the World)
    Description
    To evaluate the safety and tolerability of anifrolumab compared with placebo in participants with CLE.
    Time Frame
    Screening (up to and including 42 days before Day 1) until Safety Follow-up Period (12 weeks from Week 52/ EDV)

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    70 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Participants are eligible to be included in the study only if all of the following criteria apply: Participants must have a confirmed diagnosis of CLE. Diagnosis must be clinically and histologically confirmed with the following: CLASI-A total score ≥ 10 points at Screening and confirmed at randomization. Combined CLASI-A score for Erythema and Scale/Hypertrophy components ≥ 7 points. They should have experienced inadequate response or be intolerant to anti-malarial therapy. In case an anti-malarial treatment was never given, they should have tried one of the following medications for CLE: topical calcineurin inhibitors, systemic glucocorticoids, or a conventional immunosuppressant. Participants should have no medical history or signs or symptoms of active or prior tuberculosis infection (TB) and the same should reflect in chest radiograph or a chest CT scan result. No history of latent TB prior to initial Screening Visit. The participant must undergo an IFN-γ release assay IGRA (e.g., QFT-G test) test for TB. Contraceptive use by males and females should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. Females who have been or are sexually active with an intact cervix must have documentation of a cervical cancer screening as per local guidelines (Pap smear or HPV tests). Participants should have a COVID-19 negative PCR or antigen test result as per local policies at Screening. They should also not have had known or suspected COVID-19 exposure within 2 weeks prior to screening based on the COVID-19 questionnaire. If there is a known or suspected exposure, a participant must be negative upon retest obtained after 2 weeks and must remain asymptomatic for inclusion in the study. Exclusion criteria: Participants are excluded from the study if any of the following criteria apply: History or evidence of suicidal ideation. Severe or life-threatening SLE. Active SLE or Sjögren's Syndrome. Any active skin conditions other than CLE that may interfere with the study. History of recurrent infection requiring hospitalization and IV antibiotics. Known history of primary immunodeficiency, splenectomy, or any underlying condition that makes the participant prone to infection, or a positive result for HIV infection at Screening. Confirmed positive test for hepatitis B serology at screening. Presence of active hepatitis C infection. Any severe case, as defined by study guidelines, of herpes zoster infection. Any clinical cytomegalovirus (CMV) or Epstein-Barr virus infection that has not completely resolved. Any severe case, as defined by study guidelines, of herpes zoster infection at any time prior to randomization (Day 1). Any herpes zoster infection that has not completely resolved within 12 weeks prior to signing the informed consent form (ICF). Any clinical CMV or Epstein Barr virus infection that has not completely resolved within 12 weeks prior to signing the ICF. Clinically significant chronic infection within 8 weeks prior to signing the ICF or any infection requiring hospitalization or treatment with IV anti-infectives not completed at least 4 weeks prior to signing the ICF. COVID-19 infection History of severe COVID-19 infection or any prior COVID-19 infection with documented long COVID-19 and/or clinically significant unresolved complications due to COVID-19 infection. Mild/asymptomatic COVID-19 infection within the last 6 weeks prior to first dosing. Confirmed or probable COVID-19 infection based on clinical symptoms and radiologic imaging within 3 months prior to Day 1. COVID-19 vaccine received within 30 days of randomization (Day 1). Participants who do not meet the study restrictions for using all biologics including anifrolumab, B- cell depleting therapies (eg, rituximab), and investigational product for CLE. A known history of allergy or reaction to any component of the study intervention formulation or history of anaphylaxis to any human gamma globulin therapy. Any history of an anaphylactic reaction to human proteins, or monoclonal antibodies. At screening, if participants do not meet the eligibility criteria assessed based on laboratory test results e.g tests for total bilirubin, serum creatinine etc.
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    AstraZeneca Clinical Study Information Center
    Phone
    1-877-240-9479
    Email
    information.center@astrazeneca.com

    12. IPD Sharing Statement

    Plan to Share IPD
    Yes
    IPD Sharing 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 Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. "Yes", indicates that AZ are accepting requests for IPD, but this does not mean all requests will be approved.
    IPD Sharing Time Frame
    AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA/PhRMA Data-Sharing Principles. For details of our timelines, please refer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
    IPD Sharing Access Criteria
    When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. A Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.
    IPD Sharing URL
    https://vivli.org/

    Learn more about this trial

    A Study to Investigate the Efficacy and Safety of Anifrolumab in Adults With Chronic and/or Subacute Cutaneous Lupus Erythematosus

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