xml: <clinical_study>
    <!-- This xml conforms to an XML Schema at:
      https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
    <required_header>
      <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
      <link_text>Link to the current ClinicalTrials.gov record.</link_text>
      <url>https://clinicaltrials.gov/ct2/show/NCT06015737</url>
    </required_header>
    <id_info>
      <org_study_id>D346BC00001</org_study_id>
      <secondary_id>2021-003698-70</secondary_id>
      <nct_id>NCT06015737</nct_id>
    </id_info>
    <brief_title>A Study to Investigate the Efficacy and Safety of Anifrolumab in Adults With Chronic and/or Subacute Cutaneous Lupus Erythematosus</brief_title>
    <acronym>LAVENDER</acronym>
    <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</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>AstraZeneca</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Parexel</agency>
        <agency_class>Industry</agency_class>
      </collaborator>
    </sponsors>
    <source>AstraZeneca</source>
    <oversight_info>
      <has_dmc>Yes</has_dmc>
      <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        This study aims to evaluate the efficacy and safety of a subcutaneous (SC) treatment regimen&#xD;
        of dose A of anifrolumab versus placebo in adult participants with cutaneous lupus&#xD;
        erythematosus (CLE).&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        The study will have a randomized, double-blind, placebo-controlled design, followed by an&#xD;
        open-label treatment period.&#xD;
  &#xD;
        The study will include:&#xD;
  &#xD;
          -  Screening Period (within 6-weeks [42 days] prior to randomization).&#xD;
  &#xD;
          -  Double-blinded Treatment Period (24 weeks)&#xD;
  &#xD;
          -  Open-label Treatment Period (28 weeks)&#xD;
  &#xD;
          -  Safety Follow-up Period (12 weeks)&#xD;
  &#xD;
        Eligible participants will be randomized in a 1:1 ratio to receive either dose A of&#xD;
        anifrolumab or placebo through SC route.&#xD;
  &#xD;
        The study duration for a participant will be a maximum of 71 weeks.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">October 25, 2023</start_date>
    <completion_date type="Anticipated">December 16, 2026</completion_date>
    <primary_completion_date type="Anticipated">March 25, 2026</primary_completion_date>
    <phase>Phase 3</phase>
    <study_type>Interventional</study_type>
    <study_design_info>
      <allocation>Randomized</allocation>
      <intervention_model>Parallel Assignment</intervention_model>
      <intervention_model_description>This is a parallel group treatment study with two arms.</intervention_model_description>
      <primary_purpose>Treatment</primary_purpose>
      <masking>Double (Participant, Investigator)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>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)</measure>
      <time_frame>At Week 24</time_frame>
      <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.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Number of participants with CLASI-70 response (European Union and Rest of the World)</measure>
      <time_frame>At Week 24</time_frame>
      <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.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Percent change from baseline in total erythema score (United States, European Union and Rest of the World)</measure>
      <time_frame>At Week 24</time_frame>
      <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.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Percent change from baseline in total scale/hypertrophy score (United States, European Union and Rest of the World)</measure>
      <time_frame>At Week 24</time_frame>
      <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.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Number of participants with CLASI-A Responder Index-7 (CRI-7) response (United States)</measure>
      <time_frame>At Week 12</time_frame>
      <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:&#xD;
  ≥ 7-point reduction from baseline in CLASI-A score.&#xD;
  Total CLASI-A score of ≤ 9. A participant who does not meet these criteria is a non-responder.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Number of participants with CLASI-70 response (European Union and Rest of the World)</measure>
      <time_frame>At Week 12</time_frame>
      <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.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Number of participants with Cutaneous Lupus Activity of Physician's Global Assessment-Revised (CLA-IGA-R) erythema score of 0 or 1 (United States)</measure>
      <time_frame>At Week 24</time_frame>
      <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.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>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)</measure>
      <time_frame>At Week 24</time_frame>
      <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.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Number of participants with ≥ 7-point reduction from baseline in CLASI-A total score (United States)</measure>
      <time_frame>At Week 24</time_frame>
      <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.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Number of participants with a total CLASI-A total score of ≤ 9 (United States)</measure>
      <time_frame>At Week 24</time_frame>
      <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.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Number of participants with CLA-IGA-R OMC score of 0 or 1 (United States)</measure>
      <time_frame>At Week 24</time_frame>
      <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.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Number of participants with CLA-IGA-R follicular activity score of 0 (United States)</measure>
      <time_frame>At Week 24</time_frame>
      <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.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change from baseline in Skindex-29+3 domain scores (United States, European Union and Rest of the World)</measure>
      <time_frame>At Week 24</time_frame>
      <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.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Number of participants with CLASI-70 responders upto Week 52 (European Union and Rest of the World)</measure>
      <time_frame>Upto Week 52</time_frame>
      <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.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Serum trough (pre-dose) concentrations of anifrolumab</measure>
      <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)</time_frame>
      <description>The Ctrough of subcutaneously administered anifrolumab in participants with chronic and/or subacute CLE will be evaluated.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Number of participants with positive antidrug antibody</measure>
      <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)</time_frame>
      <description>The immunogenicity of subcutaneously administered anifrolumab in participants with chronic and/or subacute CLE will be evaluated.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Percent change from baseline in suppression of the interferon 21 gene</measure>
      <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)</time_frame>
      <description>The pharmacodynamic of subcutaneously administered anifrolumab in participants with chronic and/or subacute CLE will be evaluated.</description>
    </secondary_outcome>
    <other_outcome>
      <measure>Number of participants with adverse events (United States, European Union and Rest of the World)</measure>
      <time_frame>Screening (up to and including 42 days before Day 1) until Safety Follow-up Period (12 weeks from Week 52/ EDV)</time_frame>
      <description>To evaluate the safety and tolerability of anifrolumab compared with placebo in participants with CLE.</description>
    </other_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">230</enrollment>
    <condition>Cutaneous Lupus Erythematosus</condition>
    <arm_group>
      <arm_group_label>Anifrolumab</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>The participants will receive dose A of anifrolumab as a SC injection from Week 0/Day 1 upto and including week 51.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Placebo</arm_group_label>
      <arm_group_type>Placebo Comparator</arm_group_type>
      <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.</description>
    </arm_group>
    <intervention>
      <intervention_type>Combination Product</intervention_type>
      <intervention_name>Anifrolumab</intervention_name>
      <description>Anifrolumab will be provided as a solution for injection in accessorized pre-filled syringe (aPFS).</description>
      <arm_group_label>Anifrolumab</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>Placebo</intervention_name>
      <description>Matching placebo solution for injection in aPFS.</description>
      <arm_group_label>Placebo</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
          Participants are eligible to be included in the study only if all of the following criteria&#xD;
          apply:&#xD;
  &#xD;
            -  Participants must have a confirmed diagnosis of CLE. Diagnosis must be clinically and&#xD;
               histologically confirmed with the following:&#xD;
  &#xD;
                 -  CLASI-A total score ≥ 10 points at Screening and confirmed at randomization.&#xD;
  &#xD;
                 -  Combined CLASI-A score for Erythema and Scale/Hypertrophy components ≥ 7 points.&#xD;
  &#xD;
                 -  They should have experienced inadequate response or be intolerant to&#xD;
                    anti-malarial therapy.&#xD;
  &#xD;
                 -  In case an anti-malarial treatment was never given, they should have tried one of&#xD;
                    the following medications for CLE: topical calcineurin inhibitors, systemic&#xD;
                    glucocorticoids, or a conventional immunosuppressant.&#xD;
  &#xD;
            -  Participants should have no medical history or signs or symptoms of active or prior&#xD;
               tuberculosis infection (TB) and the same should reflect in chest radiograph or a chest&#xD;
               CT scan result.&#xD;
  &#xD;
                 -  No history of latent TB prior to initial Screening Visit.&#xD;
  &#xD;
                 -  The participant must undergo an IFN-γ release assay IGRA (e.g., QFT-G test) test&#xD;
                    for TB.&#xD;
  &#xD;
            -  Contraceptive use by males and females should be consistent with local regulations&#xD;
               regarding the methods of contraception for those participating in clinical studies.&#xD;
  &#xD;
            -  Females who have been or are sexually active with an intact cervix must have&#xD;
               documentation of a cervical cancer screening as per local guidelines (Pap smear or HPV&#xD;
               tests).&#xD;
  &#xD;
            -  Participants should have a COVID-19 negative PCR or antigen test result as per local&#xD;
               policies at Screening. They should also not have had known or suspected COVID-19&#xD;
               exposure within 2 weeks prior to screening based on the COVID-19 questionnaire. If&#xD;
               there is a known or suspected exposure, a participant must be negative upon retest&#xD;
               obtained after 2 weeks and must remain asymptomatic for inclusion in the study.&#xD;
  &#xD;
          Exclusion criteria:&#xD;
  &#xD;
          Participants are excluded from the study if any of the following criteria apply:&#xD;
  &#xD;
            -  History or evidence of suicidal ideation.&#xD;
  &#xD;
            -  Severe or life-threatening SLE.&#xD;
  &#xD;
            -  Active SLE or Sjögren's Syndrome.&#xD;
  &#xD;
            -  Any active skin conditions other than CLE that may interfere with the study.&#xD;
  &#xD;
            -  History of recurrent infection requiring hospitalization and IV antibiotics.&#xD;
  &#xD;
            -  Known history of primary immunodeficiency, splenectomy, or any underlying condition&#xD;
               that makes the participant prone to infection, or a positive result for HIV infection&#xD;
               at Screening.&#xD;
  &#xD;
            -  Confirmed positive test for hepatitis B serology at screening.&#xD;
  &#xD;
            -  Presence of active hepatitis C infection.&#xD;
  &#xD;
            -  Any severe case, as defined by study guidelines, of herpes zoster infection.&#xD;
  &#xD;
            -  Any clinical cytomegalovirus (CMV) or Epstein-Barr virus infection that has not&#xD;
               completely resolved.&#xD;
  &#xD;
            -  Any severe case, as defined by study guidelines, of herpes zoster infection at any&#xD;
               time prior to randomization (Day 1).&#xD;
  &#xD;
            -  Any herpes zoster infection that has not completely resolved within 12 weeks prior to&#xD;
               signing the informed consent form (ICF).&#xD;
  &#xD;
            -  Any clinical CMV or Epstein Barr virus infection that has not completely resolved&#xD;
               within 12 weeks prior to signing the ICF.&#xD;
  &#xD;
            -  Clinically significant chronic infection within 8 weeks prior to signing the ICF or&#xD;
               any infection requiring hospitalization or treatment with IV anti-infectives not&#xD;
               completed at least 4 weeks prior to signing the ICF.&#xD;
  &#xD;
            -  COVID-19 infection&#xD;
  &#xD;
                 -  History of severe COVID-19 infection or any prior COVID-19 infection with&#xD;
                    documented long COVID-19 and/or clinically significant unresolved complications&#xD;
                    due to COVID-19 infection.&#xD;
  &#xD;
                 -  Mild/asymptomatic COVID-19 infection within the last 6 weeks prior to first&#xD;
                    dosing.&#xD;
  &#xD;
                 -  Confirmed or probable COVID-19 infection based on clinical symptoms and&#xD;
                    radiologic imaging within 3 months prior to Day 1.&#xD;
  &#xD;
                 -  COVID-19 vaccine received within 30 days of randomization (Day 1).&#xD;
  &#xD;
            -  Participants who do not meet the study restrictions for using all biologics including&#xD;
               anifrolumab, B- cell depleting therapies (eg, rituximab), and investigational product&#xD;
               for CLE.&#xD;
  &#xD;
            -  A known history of allergy or reaction to any component of the study intervention&#xD;
               formulation or history of anaphylaxis to any human gamma globulin therapy.&#xD;
  &#xD;
            -  Any history of an anaphylactic reaction to human proteins, or monoclonal antibodies.&#xD;
  &#xD;
            -  At screening, if participants do not meet the eligibility criteria assessed based on&#xD;
               laboratory test results e.g tests for total bilirubin, serum creatinine etc.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>70 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_contact>
      <last_name>AstraZeneca Clinical Study Information Center</last_name>
      <phone>1-877-240-9479</phone>
      <email>information.center@astrazeneca.com</email>
    </overall_contact>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 1, 2023</study_first_submitted>
    <study_first_submitted_qc>August 22, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 29, 2023</study_first_posted>
    <last_update_submitted>August 22, 2023</last_update_submitted>
    <last_update_submitted_qc>August 22, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 29, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>Lupus erythematosus</keyword>
    <keyword>Cutaneous lupus erythematosus</keyword>
    <keyword>anifrolumab</keyword>
    <keyword>Cutaneous Lupus Erythematosus Disease Area Severity Index</keyword>
    <keyword>Cutaneous Lupus Erythematosus Disease Area Severity Index responder index 7</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Lupus Erythematosus, Systemic</mesh_term>
      <mesh_term>Lupus Erythematosus, Cutaneous</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>Yes</sharing_ipd>
      <ipd_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.&#xD;
  &quot;Yes&quot;, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be approved.</ipd_description>
      <ipd_info_type>Study Protocol</ipd_info_type>
      <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
      <ipd_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_time_frame>
      <ipd_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_access_criteria>
      <ipd_url>https://vivli.org/</ipd_url>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: download date: ClinicalTrials.gov processed this data on September 20, 2023
  link text: Link to the current ClinicalTrials.gov record.
  url: https://clinicaltrials.gov/ct2/show/NCT06015737
  org study id: D346BC00001
  secondary id: 2021-003698-70
  nct id: NCT06015737
  lead sponsor: 
  collaborator: 
  has dmc: Yes
  is fda regulated drug: Yes
  is fda regulated device: No
  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).
  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.
  allocation: Randomized
  intervention model: Parallel Assignment
  intervention model description: This is a parallel group treatment study with two arms.
  primary purpose: Treatment
  masking: Double (Participant, Investigator)
  measure: 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)
  time frame: At Week 24
  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.
  measure: Number of participants with CLASI-70 response (European Union and Rest of the World)
  time frame: At Week 24
  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.
  measure: Percent change from baseline in total erythema score (United States, European Union and Rest of the World)
  time frame: At Week 24
  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.
  measure: Percent change from baseline in total scale/hypertrophy score (United States, European Union and Rest of the World)
  time frame: At Week 24
  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.
  measure: Number of participants with CLASI-A Responder Index-7 (CRI-7) response (United States)
  time frame: At Week 12
  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.
  measure: Number of participants with CLASI-70 response (European Union and Rest of the World)
  time frame: At Week 12
  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.
  measure: Number of participants with Cutaneous Lupus Activity of Physician's Global Assessment-Revised (CLA-IGA-R) erythema score of 0 or 1 (United States)
  time frame: At Week 24
  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.
  measure: 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)
  time frame: At Week 24
  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.
  measure: Number of participants with ≥ 7-point reduction from baseline in CLASI-A total score (United States)
  time frame: At Week 24
  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.
  measure: Number of participants with a total CLASI-A total score of ≤ 9 (United States)
  time frame: At Week 24
  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.
  measure: Number of participants with CLA-IGA-R OMC score of 0 or 1 (United States)
  time frame: At Week 24
  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.
  measure: Number of participants with CLA-IGA-R follicular activity score of 0 (United States)
  time frame: At Week 24
  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.
  measure: Change from baseline in Skindex-29+3 domain scores (United States, European Union and Rest of the World)
  time frame: At Week 24
  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.
  measure: Number of participants with CLASI-70 responders upto Week 52 (European Union and Rest of the World)
  time frame: Upto Week 52
  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.
  measure: Serum trough (pre-dose) concentrations of anifrolumab
  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)
  description: The Ctrough of subcutaneously administered anifrolumab in participants with chronic and/or subacute CLE will be evaluated.
  measure: Number of participants with positive antidrug antibody
  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)
  description: The immunogenicity of subcutaneously administered anifrolumab in participants with chronic and/or subacute CLE will be evaluated.
  measure: Percent change from baseline in suppression of the interferon 21 gene
  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)
  description: The pharmacodynamic of subcutaneously administered anifrolumab in participants with chronic and/or subacute CLE will be evaluated.
  measure: Number of participants with adverse events (United States, European Union and Rest of the World)
  time frame: Screening (up to and including 42 days before Day 1) until Safety Follow-up Period (12 weeks from Week 52/ EDV)
  description: To evaluate the safety and tolerability of anifrolumab compared with placebo in participants with CLE.
  arm group label: Anifrolumab
  arm group type: Experimental
  description: The participants will receive dose A of anifrolumab as a SC injection from Week 0/Day 1 upto and including week 51.
  arm group label: Placebo
  arm group type: Placebo Comparator
  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: Anifrolumab
  description: Anifrolumab will be provided as a solution for injection in accessorized pre-filled syringe (aPFS).
  arm group label: Anifrolumab
  intervention type: Other
  intervention name: Placebo
  description: Matching placebo solution for injection in aPFS.
  arm group label: Placebo
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 70 Years
  healthy volunteers: No
  last name: AstraZeneca Clinical Study Information Center
  phone: 1-877-240-9479
  email: information.center@astrazeneca.com
  responsible party type: Sponsor
  mesh term: Lupus Erythematosus, Systemic
  mesh term: Lupus Erythematosus, Cutaneous
  sharing ipd: Yes
  ipd 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 info type: Study Protocol
  ipd info type: Statistical Analysis Plan (SAP)
  ipd 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 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 url: https://vivli.org/