A 2-stage, Phase III Study to Investigate the Efficacy and Safety of Anifrolumab in Adults With Chronic and/or Subacute Cutaneous Lupus Erythematosus

Cutaneous Lupus Erythematosus Clinical Trial

— 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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06015737
• Other study ID #: D346BC00001
• Secondary ID: 2021-003698-70
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: May 9, 2024
• Est. completion date: December 21, 2027

Study information

• Verified date: April 2024
• Source: AstraZeneca
• Contact: AstraZeneca Clinical Study Information Center
• Phone: 1-877-240-9479
• Email: information.center[@]astrazeneca.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Description:

The primary objectives of the study are to evaluate the efficacy of anifrolumab compared with placebo in reducing skin disease in participants with active chronic and/or subacute CLE who are refractory and/or intolerant to antimalarial therapy. The secondary objectives of the study are to evaluate additional efficacy parameters of anifrolumab, safety, tolerability, quality of life, pharmacokinetics, pharmacodynamics, and immunogenicity. Stage 1 and Stage 2 of the study will have broadly identical study designs with the exception of sample size. Both Stages of the study will have a randomized, double-blind, placebo-controlled design, followed by an open-label treatment period.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 460
• Est. completion date: December 21, 2027
• Est. primary completion date: December 21, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.
• CLA-IGA-R erythema score of = 3 and CLA-IGA-R-OMC score of = 1 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.
• Participants should have a coronavirus disease 2019 (COVID-19) negative PCR or antigen test result as per local policies at Screening.

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 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

Related Conditions & MeSH terms

• Cutaneous Lupus Erythematosus
• Lupus Erythematosus, Cutaneous
• Lupus Erythematosus, Systemic

Intervention

Combination Product:
• Anifrolumab
Anifrolumab will be provided as a solution for injection in accessorized pre-filled syringe (aPFS).

Other:
• Placebo
Matching placebo solution for injection in aPFS.

Combination Product:
• Anifrolumab
Anifrolumab will be provided as a solution for injection in accessorized pre-filled syringe (aPFS).

Other:
• Placebo
Matching placebo solution for injection in aPFS.

Locations

Country	Name	City	State
Argentina	Research Site	Ciudad de Buenos Aires
Argentina	Research Site	Córdoba
Argentina	Research Site	Quilmes
Australia	Research Site	Box Hill
Australia	Research Site	Westmead
Australia	Research Site	Woolloongabba
Austria	Research Site	Innsbruck
Austria	Research Site	Linz
Austria	Research Site	Sankt Pölten
Brazil	Research Site	Belo Horizonte
Bulgaria	Research Site	Sofia
Chile	Research Site	Santiago
China	Research Site	Baotou
China	Research Site	Beijing
China	Research Site	Beijing
China	Research Site	Chongqing
China	Research Site	Guangzhou
China	Research Site	Hangzhou
China	Research Site	Jinan
China	Research Site	Nanjing
China	Research Site	Shanghai
China	Research Site	Shijiazhuang
China	Research Site	Wuhan
Colombia	Research Site	Barranquilla
Colombia	Research Site	Chia
France	Research Site	Lyon Cedex 03
France	Research Site	Nice
France	Research Site	Paris
France	Research Site	Paris
France	Research Site	Paris
France	Research Site	Paris
France	Research Site	Toulouse Cedex 9
Germany	Research Site	Berlin
Germany	Research Site	Bochum
Germany	Research Site	Dresden
Germany	Research Site	Hannover
Germany	Research Site	Leipzig
Germany	Research Site	Mainz
Germany	Research Site	Wuppertal
Greece	Research Site	Athens
Greece	Research Site	Athens
Greece	Research Site	Athens
Italy	Research Site	Brescia
Italy	Research Site	Florence
Italy	Research Site	Napoli
Italy	Research Site	Torrette
Netherlands	Research Site	Rotterdam
Philippines	Research Site	Lipa
Philippines	Research Site	Manila
Poland	Research Site	Olsztyn
Poland	Research Site	Poznan
Poland	Research Site	Warszawa
Spain	Research Site	Barcelona
Spain	Research Site	Madrid
Spain	Research Site	Madrid
Taiwan	Research Site	Kaohsiung
Taiwan	Research Site	Taichung
United States	Research Site	Ann Arbor	Michigan
United States	Research Site	Boston	Massachusetts
United States	Research Site	Brooklyn	New York
United States	Research Site	Charlottesville	Virginia
United States	Research Site	Fort Lauderdale	Florida
United States	Research Site	Miami	Florida
United States	Research Site	Miami	Florida
United States	Research Site	Orange	California
United States	Research Site	Phoenix	Arizona
United States	Research Site	Plantation	Florida
United States	Research Site	Portland	Oregon
United States	Research Site	Rochester	New York

Sponsors (2)

Lead Sponsor	Collaborator
AstraZeneca	Parexel

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Brazil,  Bulgaria,  Chile,  China,  Colombia,  France,  Germany,  Greece,  Italy,  Netherlands,  Philippines,  Poland,  Spain,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Stage 1 and Stage 2 (US, EU and ROW): 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 (13 weeks from Week 52/ EDV)
Primary	Stage 1 and Stage 2 (United States [US]): Number of participants with Cutaneous Lupus Activity of Investigator's Global Assessment-Revised (CLA-IGA-R) erythema score of 0 or 1 and at least a 2- point reduction relative to baseline	The CLA-IGA-R is an assessment tool that scores the three key disease components (erythema; other morphological characteristics [OMC] 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 (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. CLA-IGA-R erythema responder is defined as a participant who achieves a CLA-IGA-R erythema score of 0 or 1 and at least a 2-point reduction relative to baseline. Otherwise, the participant is considered a non-responder.	At Week 24
Primary	Stage 1 and Stage 2 (European Union [EU]/Rest of the World [ROW]: Number of participants with a 70% reduction relative to baseline in the Cutaneous Lupus Erythematosus Disease Area and Severity Index-Activity (CLASI-A) score	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.	At Week 24
Secondary	Stage 1 and Stage 2 (US): Number of participants who achieve a CLA-IGA-R OMC score of 0 or 1 and at least a 1-point reduction relative to baseline	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. A responder (yes/no) is defined as a participant who achieves a CLA-IGA-R OMC score of 0 or 1 and at least a 1-point reduction relative to baseline. Otherwise, the participant is considered a non-responder.	At Week 24
Secondary	Stage 1 and Stage 2 (US): Number of participants who achieve a CLA-IGA-R OMC score of 0.	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. CLA-IGA-R OMC complete response is defined as a participant who scores 0. Otherwise, the participant is a non-responder. Only participants with CLA-IGA-OMC = 3 at baseline will be included in the analysis.	At Week 24
Secondary	Stage 1 and Stage 2 (US): Number of participants with CLA-IGA-R follicular activity score of 0	The CLA-IGA-R is a 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. On all IGA scales, a decrease in score relates to an improvement in signs and symptoms. A responder (yes/no) is defined as a participant who achieves a CLA-IGA-R follicular activity score of 0. Otherwise, the participant is a non-responder. Only participants with follicular activity score of 1 at baseline will be included in the analysis.	At Week 24
Secondary	Stage 1 and Stage 2 (EU/ROW): Percent change from baseline in total CLASI-A erythema score	The Cutaneous Lupus Erythematosus Disease Area and Severity Index-Activity (CLASI-A) is a validated index used for assessing the cutaneous lesions of SLE. The CLASI-A erythema score is interpreted as follows: 0-absent; 1-pink; faint erythema; 2-red; 3-dark red; purple/violaceous/crusted/ hemorrhagic	At Week 24
Secondary	Stage 1 and Stage 2 (EU/ROW): Percent change from baseline in total CLASI-A scale/hypertrophy score	The CLASI-A 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.	At Week 24
Secondary	Stage 1 and Stage 2 (US): Number of participants with CLA-IGA-R erythema score of 0 or 1 and at least a 2-point reduction relative to baseline, or a CLA-IGA-R OMC score of 0 or 1 and at least a 1-point reduction relative to baseline	The CLA-IGA-R is a tool that scores the three key disease components (erythema; OMC and follicular activity) of CLE independently. The CLA-IGA-R erythema and OMC are 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. A responder (yes/no) is defined as a participant who achieves either a CLA-IGA-R erythema score of 0 or 1 and at least a 2-point reduction relative to baseline, or a CLA-IGA-R OMC score of 0 or 1 and at least a 1-point reduction relative to baseline. Otherwise, the participant is a non-responder. On all IGA scales, a decrease in score relates to an improvement in signs and symptoms.	At Week 24
Secondary	Stage 1 and Stage 2 (US): Number of participants with CLA-IGA-R erythema score of 0 or 1 and at least a 2-point reduction relative to baseline	The CLA-IGA-R is a tool that scores the three key disease components (erythema; OMC 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 (0 indicates clear, 1 is almost clear, 2 is mild, 3 is moderate, and 4 indicates severe CLE). A responder is defined as a participant who achieves a CLA-IGA-R erythema score of 0 or 1 and at least a 2-point reduction relative to baseline. Otherwise, the participant is a non-responder. On all IGA scales, a decrease in score relates to an improvement in signs and symptoms.	At Week 12
Secondary	Stage 1 and Stage 2 (US): Number of participants with CLA-IGA-R OMC score of 0 or 1 and at least a 1-point reduction relative to baseline	The CLA-IGA-R is a 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 (0 indicates clear, 1 is almost clear, 2 is mild, 3 is moderate, and 4 indicates severe CLE). A responder (yes/no) is defined as a participant who achieves a CLA- IGA-R OMC score of 0 or 1 and at least a 1-point reduction relative to baseline. Otherwise, the participant is a non-responder. On all IGA scales, a decrease in score relates to an improvement in signs and symptoms.	At Week 12
Secondary	Stage 1 and Stage 2 (EU/ROW): 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
Secondary	Stage 1 and Stage 2 (US/EU/ROW): Change from baseline in Skindex-29+3 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. 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.	At Week 24
Secondary	Stage 1 and Stage 2 (US/EU/ROW): 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)
Secondary	Stage 1 and Stage 2 (US/EU/ROW): 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)
Secondary	Stage 1 and Stage 2 (US/EU/ROW): 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)
Secondary	Stage 2 (US/EU/ROW): 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. 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.	At Week 24
Secondary	Stage 2 (US): Number of participants who are CLA-IGA-R erythema responders from Week 24 up to and including Week 52	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 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 responder is defined as a participant who achieves a CLA- IGA-R erythema score of 0 or 1 and at least a 2-point reduction relative to baseline. Otherwise, the participant is a non-responder. Amongst participants randomized to anifrolumab during the double-blind treatment period, the number of participants who maintained a CLA-IGA-R erythema response from Week 24 up to Week 52 will be evaluated.	Up to Week 52
Secondary	Stage 2 (EU): Number of participants who are CLASI-70 responders up to and including Week 52	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 up to Week 52 will be evaluated.	Up to Week 52