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

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.

This study aims to evaluate the efficacy and safety of subcutaneous (SC) anifrolumab versus placebo in adult participants with chronic and/or subacute cutaneous lupus erythematosus (CLE).

Study Overview

• Status: Active, not recruiting
• Conditions: Cutaneous Lupus Erythematosus
• Intervention / Treatment: Combination product: Anifrolumab; Other: Placebo

Detailed Description

This is 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 CLE who are refractory and/or intolerant to antimalarial therapy. The study has a randomized, 24-week double-blind, placebo-controlled study period (Week 0 to Week 23), to evaluate the efficacy and safety of anifrolumab. The double-blind study period will be followed by an open-label, uncontrolled treatment period in which all participants will receive treatment with anifrolumab from Week 24 to Week 51. After the open-label treatment period, participants will enter a 12-week Safety Follow-up Period.

• Study Type: Interventional
• Enrollment (Actual): 306
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Ciudad de Buenos Aires, Argentina, 1221
    • Research Site
  • Córdoba, Argentina, 5000
    • Research Site
  • Córdoba, Argentina, X5004BAL
    • Research Site
  • Quilmes, Argentina, 1878
    • Research Site
  • San Miguel, Argentina, 1663
    • Research Site
• Australia
  • Kogarah, Australia, 3168
    • Research Site
  • Melbourne, Australia, 3004
    • Research Site
  • Mitcham, Australia, 3132
    • Research Site
  • Westmead, Australia, 2145
    • Research Site
  • Woolloongabba, Australia, 04102
    • Research Site
• Austria
  • Graz, Austria, 8036
    • Research Site
  • Innsbruck, Austria, 6020
    • Research Site
  • Linz, Austria, 4020
    • Research Site
  • Vienna, Austria, 1130
    • Research Site
• Brazil
  • Belo Horizonte, Brazil, 30150-221
    • Research Site
  • Porto Alegre, Brazil, 90035903
    • Research Site
  • Rio de Janeiro, Brazil, 22470-220
    • Research Site
  • Salvador, Brazil, 40150-150
    • Research Site
  • São Paulo, Brazil, 05403-000
    • Research Site
• Bulgaria
  • Sofia, Bulgaria, 1784
    • Research Site
  • Sofia, Bulgaria, 1463
    • Research Site
  • Sofia, Bulgaria, 1528
    • Research Site
• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 1M9
      • Research Site
  • Ontario
    • Hamilton, Ontario, Canada, L8N 3Z5
      • Research Site
    • Toronto, Ontario, Canada, M5T 2S8
      • Research Site
• Chile
  • Osorno, Chile, 200025
    • Research Site
  • Santiago, Chile, 7500571
    • Research Site
  • Santiago, Chile, 130021
    • Research Site
• China
  • Changchun, China, 130021
    • Research Site
  • Changsha, China, 410011
    • Research Site
  • Chengdu, China, 610021
    • Research Site
  • Chongqing, China, 400016
    • Research Site
  • Dongguan, China, 523059
    • Research Site
  • Guangzhou, China, 510120
    • Research Site
  • Heilongjiang, China, 150086
    • Research Site
  • Jinan, China, 250022
    • Research Site
  • Shanghai, China, 200025
    • Research Site
  • Shanghai, China, 200443
    • Research Site
  • Shenzhen, China, 518053
    • Research Site
  • Shenzhen, China, 518020
    • Research Site
  • Shenzhen, China, 518052
    • Research Site
  • Zhuzhou, China, 412007
    • Research Site
  • Ürümqi, China, CN-830004
    • Research Site
• Colombia
  • Barranquilla, Colombia, 080020
    • Research Site
  • Bogotá, Colombia, 110221
    • Research Site
• Denmark
  • Aarhus, Denmark, 641-8510
    • Research Site
  • Copenhagen, Denmark, 2100
    • Research Site
• France
  • Bois-Guillaume, France, 76031
    • Research Site
  • Dijon, France, 21000
    • Research Site
  • Lyon, France, 69437
    • Research Site
  • Montivilliers, France, 76290
    • Research Site
  • Nantes, France, 44000
    • Research Site
  • Paris, France, 75010
    • Research Site
  • Paris, France, 75014
    • Research Site
  • Paris, France, 75013
    • Research Site
  • Paris, France, 75970
    • Research Site
  • Poitiers, France, 86000, FR
    • Research Site
  • Toulouse, France, 31059
    • Research Site
• Germany
  • Berlin, Germany, 10117
    • Research Site
  • Bochum, Germany, 44791
    • Research Site
  • Dresden, Germany, 01307
    • Research Site
  • Erlangen, Germany, 91054
    • Research Site
  • Essen, Germany, 45147
    • Research Site
  • Freiburg im Breisgau, Germany, 79104
    • Research Site
  • Hanover, Germany, 30625
    • Research Site
  • Kiel, Germany, 24105
    • Research Site
  • Leipzig, Germany, 04103
    • Research Site
  • Mainz, Germany, 55131
    • Research Site
  • Marburg, Germany, 35043
    • Research Site
  • Regensburg, Germany, 93053
    • Research Site
  • Wuppertal, Germany, 42283
    • Research Site
• Greece
  • Athens, Greece, 12462
    • Research Site
  • Athens, Greece, 16121
    • Research Site
• Italy
  • Brescia, Italy, 25123
    • Research Site
  • Cona, Italy, 44124
    • Research Site
  • Florence, Italy, 50121
    • Research Site
  • Milan, Italy, 20132
    • Research Site
  • Naples, Italy, 80138
    • Research Site
  • Reggio Emilia, Italy, 42123
    • Research Site
  • Roma, Italy, 00144
    • Research Site
  • Rome, Italy, 00168
    • Research Site
• Japan
  • Chūōku, Japan, 104-8560
    • Research Site
  • Fukuoka, Japan, 812-8582
    • Research Site
  • Kanazawa, Japan, 920-8641
    • Research Site
  • Kita-gun, Japan, 761-0793
    • Research Site
  • Nagoya, Japan, 457-8510
    • Research Site
  • Nagoya, Japan, 467-8602
    • Research Site
  • Wakayama, Japan, 641-8510
    • Research Site
  • Yokohama, Japan, 232-0024
    • Research Site
  • tabashi City, Japan, 173-8606
    • Research Site
• Mexico
  • Guadalajara, Mexico, 44340
    • Research Site
  • Guadalajara, Mexico, 44610
    • Research Site
  • Mexico City, Mexico, 07760
    • Research Site
  • Veracruz, Mexico, 91910
    • Research Site
• Netherlands
  • Breda, Netherlands, 4818 CK
    • Research Site
  • Rotterdam, Netherlands, 3015 GD
    • Research Site
• New Zealand
  • Papatoetoe, New Zealand, 2025
    • Research Site
• Philippines
  • Iloilo City, Philippines, 5000
    • Research Site
  • Lipa, Philippines, 4217
    • Research Site
  • Manila, Philippines, 1000
    • Research Site
• Poland
  • Katowice, Poland, 40-851
    • Research Site
  • Kielce, Poland, 25-316
    • Research Site
  • Ossy, Poland, 40-027
    • Research Site
  • Rzeszów, Poland, 35-055
    • Research Site
  • Warsaw, Poland, 02-637
    • Research Site
• Portugal
  • Braga, Portugal, 4710-243
    • Research Site
  • Lisbon, Portugal, 1649-035
    • Research Site
  • Porto, Portugal, 4099-001
    • Research Site
• Romania
  • Bucharest, Romania, 020125
    • Research Site
  • Iași, Romania, 700291
    • Research Site
• Serbia
  • Belgrade, Serbia, 11000
    • Research Site
  • Kragujevac, Serbia, 34000
    • Research Site
• Slovakia
  • Košice, Slovakia, 04001
    • Research Site
  • Piešťany, Slovakia, 92101
    • Research Site
• South Africa
  • Cape Town, South Africa, 7500
    • Research Site
  • Johannesburg, South Africa, 2193
    • Research Site
• South Korea
  • Seoul, South Korea, 03080
    • Research Site
  • Seoul, South Korea, 06591
    • Research Site
  • Seoul, South Korea, 06973
    • Research Site
• Spain
  • Barcelona, Spain, 8035
    • Research Site
  • Barcelona, Spain, 08025
    • Research Site
  • Castellon, Spain, 12004
    • Research Site
  • Granada, Spain, 18012
    • Research Site
  • L'Hospitalet de Llobregat, Spain, 08907
    • Research Site
  • Las Palmas de Gran Canaria, Spain, 35010
    • Research Site
  • Madrid, Spain, 28034
    • Research Site
  • Madrid, Spain, 28041
    • Research Site
  • Madrid, Spain, 28040
    • Research Site
  • Madrid, Spain, 28006
    • Research Site
  • Majadahonda, Spain, 28222
    • Research Site
  • Salamanca, Spain, 37007
    • Research Site
  • Seville, Spain, 41014
    • Research Site
  • Valencia, Spain, 46014
    • Research Site
  • Valencia, Spain, 46017
    • Research Site
  • Vigo, Spain, 36200
    • Research Site
• Taiwan
  • Kaohsiung City, Taiwan, 83301
    • Research Site
  • Taichung, Taiwan, 404
    • Research Site
  • Taipei, Taiwan, 10449
    • Research Site
• Thailand
  • Bangkok, Thailand, 10330
    • Research Site
  • Bangkok, Thailand, 10700
    • Research Site
  • Hat Yai, Thailand, 90110
    • Research Site
  • Khlong Luang, Thailand, 12120
    • Research Site
  • Khon Kaen, Thailand, 40002
    • Research Site
• Turkey (Türkiye)
  • Cordaleo, Turkey (Türkiye), 35575
    • Research Site
  • Istanbul, Turkey (Türkiye), 34098
    • Research Site
  • Kayseri, Turkey (Türkiye), 38039
    • Research Site
  • Samsun, Turkey (Türkiye), 55270
    • Research Site
• United Kingdom
  • Cambridge, United Kingdom, CB2 0QQ
    • Research Site
  • Leeds, United Kingdom, LS2 9JT
    • Research Site
  • London, United Kingdom, NW1 2PG
    • Research Site
  • London, United Kingdom, SE5 9RS
    • Research Site
  • London, United Kingdom, SE1 7EH
    • Research Site
  • London, United Kingdom, NW3 2QG
    • Research Site
  • Newcastle upon Tyne, United Kingdom, NE1 4LP
    • Research Site
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85028
      • Research Site
  • California
    • Covina, California, United States, 91722
      • Research Site
    • La Jolla, California, United States, 92037
      • Research Site
    • Los Angeles, California, United States, 90045
      • Research Site
    • Los Angeles, California, United States, 90089
      • Research Site
    • Orange, California, United States, 92868
      • Research Site
    • San Francisco, California, United States, 94143
      • Research Site
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Research Site
  • Connecticut
    • New Haven, Connecticut, United States, 06519
      • Research Site
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20037
      • Research Site
  • Florida
    • Fort Lauderdale, Florida, United States, 33309
      • Research Site
    • Miami, Florida, United States, 33174
      • Research Site
    • Plantation, Florida, United States, 33324
      • Research Site
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Research Site
    • Chicago, Illinois, United States, 60611
      • Research Site
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Research Site
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Research Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Research Site
    • Boston, Massachusetts, United States, 02115-5817
      • Research Site
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Research Site
    • Bloomfield Hills, Michigan, United States, 48302
      • Research Site
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Research Site
  • Nebraska
    • Omaha, Nebraska, United States, 68198-5885
      • Research Site
  • New York
    • New York, New York, United States, 10028
      • Research Site
    • Rochester, New York, United States, 14642
      • Research Site
  • North Carolina
    • Charlotte, North Carolina, United States, 28207
      • Research Site
    • Statesville, North Carolina, United States, 28625
      • Research Site
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Research Site
  • Oregon
    • Portland, Oregon, United States, 97239
      • Research Site
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Research Site
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Research Site
  • Texas
    • Dallas, Texas, United States, 75390-8843
      • Research Site
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • Research Site
    • Roanoke, Virginia, United States, 24016
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Key inclusion criteria:

• 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.
  • Inadequate response or intolerant to antimalarial therapy.
• 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.
• Contraceptive use by males and females should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.

Key exclusion criteria:

• History or evidence of suicidal ideation.
• Severe or life-threatening Systemic lupus erythematosus (SLE).
• Active SLE or Sjögren's Syndrome.
• Any active skin conditions other than CLE that may interfere with the study.
• History of, or current diagnosis of, catastrophic antiphospholipid syndrome (APS).
• History of recurrent infection requiring hospitalization and IV antibiotics.
• COVID-19 infection.
• 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.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Anifrolumab; Participants will receive anifrolumab as a SC injection from Week 0/Day 1 up to Week 51.	Combination product: Anifrolumab; Anifrolumab will be provided as a solution for injection in accessorized pre-filled syringe (aPFS).
Placebo Comparator: Placebo; Participants will receive placebo as a SC injection from Week 0/Day 1 up to Week 23. From Week 24 the participants will receive anifrolumab up to and including Week 51.	Other: Placebo; Matching placebo solution for injection in aPFS.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with a 70% reduction relative to baseline in the Cutaneous Lupus Erythematosus Disease Area and Severity Index-Activity (CLASI-A) score	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. 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.	At Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in total CLASI-A score	The CLASI-A is a validated index used for assessing the cutaneous lesions of SLE.	At Week 24
Number of participants with CLASI-70 response	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.	At Week 12
Number of participants with ≥ 7-point reduction from baseline in CLASI-A total score	The CLASI is a validated index used for assessing the cutaneous lesions of SLE. A 7-point reduction CLASI-A is established as clinically meaningful improvement in disease for CLE and as being impactful for patients.	At Week 12
Number of participants with CLASI-50 response	The CLASI is a validated index used for assessing the cutaneous lesions of SLE. CLASI-50 responder is defined as a responder (yes/no) is defined as a participant who achieves at least a 50% reduction relative to baseline in CLASI-A score. Otherwise, the participant is a non-responder.	At Week 12 and Week 24
Number of participants who are sustained CLASI-70 responders	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, the number of participants who maintained a CLASI-70 response from Week 24 up to Week 52 will be evaluated.	Up to Week 52
Serum trough (pre-dose) concentrations of anifrolumab	The Ctrough of subcutaneously administered anifrolumab in participants with chronic and/or subacute CLE will be evaluated.	Double-blind: Pre-dose on Day 1 (Week 0), Weeks 1, 4, 12, 24; Open-label: Weeks 40, and 52 or early discontinuation visit [EDV] and follow-up visit (13 Weeks after last dose)
Number of participants with positive antidrug antibody	The immunogenicity of subcutaneously administered anifrolumab in participants with chronic and/or subacute CLE will be evaluated.	Double-blind: Pre-dose on Day 1 (Week 0), Weeks 4, 12, and 24; Open-label: Pre-dose on Weeks 40, and 52 or EDV and follow-up visit (13 weeks after last dose)
Percent change from baseline in suppression of the Interferon 21-gene	The pharmacodynamics of subcutaneously administered anifrolumab in participants with chronic and/or subacute CLE will be evaluated.	Double-blind: Day 1 (Week 0), Week 1, 4, 12, and 24; Open-label; Week 40 and 52 or EDV and follow-up visit (13 weeks after last dose)
Change from baseline in Skindex-29+3 Symptom domain scores	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.	At Week 24
Change from baseline in Skindex-29+3 Emotion domain scores	The Skindex-29+3 is based on a previous instrument, the Skindex-29 and has been modified to include items related to CLE.	At Week 24
Change from baseline in Skindex-29+3 Function domain scores	The Skindex-29+3 is based on a previous instrument, the Skindex-29 and has been modified to include items related to CLE.	At Week 24
Change from baseline in Skindex-29+3 Lupus-Specific domain scores	The Skindex-29+3 is based on a previous instrument, the Skindex-29 and has been modified to include items related to CLE.	At Week 24
Change from baseline in Skindex-29+3 Total score	The Skindex-29+3 is based on a previous instrument, the Skindex-29 and has been modified to include items related to CLE.	At Week 24
Time from IP start date to CLASI-70 response.	To assess the efficacy of anifrolumab compared with placebo on the onset of reduction in skin manifestations in participants with chronic and/or subacute CLE.	From Week 0/Day 1 up to Week 24
Time from IP start date to CLASI-50 response.	To assess the efficacy of anifrolumab compared with placebo on the onset of reduction in skin manifestations in participants with chronic and/or subacute CLE.	From Week 0/Day 1 up to Week 24

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with adverse events	To evaluate the safety and tolerability of anifrolumab compared with placebo in participants with CLE.	Screening (up to and including 42 days before Day 1) until Safety Follow-up Period (12 weeks from Week 52/EDV)

Collaborators and Investigators

• Sponsor: AstraZeneca
• Collaborators: Parexel

Study record dates

Study Major Dates

• Study Start (Actual): June 29, 2024
• Primary Completion (Estimated): December 11, 2026
• Study Completion (Estimated): August 11, 2027

Study Registration Dates

• First Submitted: August 1, 2023
• First Submitted That Met QC Criteria: August 22, 2023
• First Posted (Actual): August 29, 2023

Study Record Updates

• Last Update Posted (Actual): May 1, 2026
• Last Update Submitted That Met QC Criteria: April 30, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Cutaneous lupus erythematosus; Anifrolumab; Lupus erythematosus; Discoid lupus; Cutaneous Lupus Erythematosus Disease Area Severity Index; Subacute lupus
• Additional Relevant MeSH Terms: Connective Tissue Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Lupus Erythematosus, Cutaneous; Lupus Erythematosus, Discoid; Substandard Drugs; Pharmaceutical Preparations; anifrolumab
• Other Study ID Numbers: D346BC00001; 2021-003698-70 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD 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 Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No