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

Phase 3RecruitingNCT06015737

AstraZeneca302 enrolled

Overview

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).

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

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

302

Conditions

Cutaneous Lupus Erythematosus

Interventions

AnifrolumabCOMBINATION_PRODUCT

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

PlaceboOTHER

Matching placebo solution for injection in aPFS.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 70 Years

Medical Language ↔ Plain English

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

Locations (272)

Outcomes

Primary Outcomes

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.

Time frame: At Week 24

Secondary Outcomes

Change from baseline in total CLASI-A score

The CLASI-A is a validated index used for assessing the cutaneous lesions of SLE.

Time frame: At Week 24

Number of participants with CLASI-70 response

Time frame: 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.

Time frame: 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.

Central Contacts

AstraZeneca Clinical Study Information Center

CONTACT

1-877-240-9479 information.center@astrazeneca.com

Data from ClinicalTrials.gov

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Research Site

Glendale, Arizona, United States

WITHDRAWN

Research Site

Phoenix, Arizona, United States

RECRUITING

Research Site

Covina, California, United States

RECRUITING

Research Site

Fountain Valley, California, United States

WITHDRAWN

Research Site

La Jolla, California, United States

RECRUITING

Research Site

Los Angeles, California, United States

RECRUITING

Research Site

Los Angeles, California, United States

RECRUITING

Research Site

Orange, California, United States

RECRUITING

Research Site

Orange, California, United States

WITHDRAWN

Research Site

San Francisco, California, United States

RECRUITING

...and 262 more locations

Time frame: 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.

Time frame: 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.

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 [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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: From Week 0/Day 1 up to Week 24