Cutaneous Lupus Erythematosus
Conditions
Keywords
Lupus erythematosus, Cutaneous lupus erythematosus, Anifrolumab, Cutaneous Lupus Erythematosus Disease Area Severity Index, Subacute lupus, Discoid lupus
Brief summary
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).
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.
Interventions
COMBINATION_PRODUCTAnifrolumab
Anifrolumab will be provided as a solution for injection in accessorized pre-filled syringe (aPFS).
OTHERPlacebo
Matching placebo solution for injection in aPFS.
Sponsors
AstraZeneca
Parexel
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Intervention model description
This is a parallel group treatment study with two arms.
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with a 70% reduction relative to baseline in the Cutaneous Lupus Erythematosus Disease Area and Severity Index-Activity (CLASI-A) score | At Week 24 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in total CLASI-A score | At Week 24 | The CLASI-A is a validated index used for assessing the cutaneous lesions of SLE. |
| Number of participants with CLASI-70 response | At Week 12 | The CLASI is a validated index used for assessing the cutaneous lesions of SLE. CLASI-70 responder is defined as a participant who achieves a 70% reduction relative to baseline in CLASI-A score. Otherwise, the participant is considered a non-responder. |
| Number of participants with ≥ 7-point reduction from baseline in CLASI-A total score | At Week 12 | 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. |
| Number of participants with CLASI-50 response | At Week 12 and Week 24 | 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. |
| Number of participants who are sustained CLASI-70 responders | Up to 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, the number of participants who maintained a CLASI-70 response from Week 24 up to Week 52 will be evaluated. |
| Serum trough (pre-dose) concentrations of anifrolumab | 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) | The Ctrough of subcutaneously administered anifrolumab in participants with chronic and/or subacute CLE will be evaluated. |
| Number of participants with positive antidrug antibody | 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) | The immunogenicity of subcutaneously administered anifrolumab in participants with chronic and/or subacute CLE will be evaluated. |
| Percent change from baseline in suppression of the Interferon 21-gene | 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) | The pharmacodynamics of subcutaneously administered anifrolumab in participants with chronic and/or subacute CLE will be evaluated. |
| Change from baseline in Skindex-29+3 Symptom domain scores | At Week 24 | 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. |
| Change from baseline in Skindex-29+3 Emotion domain scores | At Week 24 | The Skindex-29+3 is based on a previous instrument, the Skindex-29 and has been modified to include items related to CLE. |
| Change from baseline in Skindex-29+3 Function domain scores | At Week 24 | The Skindex-29+3 is based on a previous instrument, the Skindex-29 and has been modified to include items related to CLE. |
| Change from baseline in Skindex-29+3 Lupus-Specific domain scores | At Week 24 | The Skindex-29+3 is based on a previous instrument, the Skindex-29 and has been modified to include items related to CLE. |
| Change from baseline in Skindex-29+3 Total score | At Week 24 | The Skindex-29+3 is based on a previous instrument, the Skindex-29 and has been modified to include items related to CLE. |
| Time from IP start date to CLASI-70 response. | From Week 0/Day 1 up to Week 24 | 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 from IP start date to CLASI-50 response. | From Week 0/Day 1 up to Week 24 | 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. |
Countries
Argentina, Australia, Austria, Brazil, Bulgaria, Canada, Chile, China, Colombia, Denmark, France, Germany, Greece, Italy, Japan, Mexico, Netherlands, New Zealand, Philippines, Poland, Portugal, Romania, Serbia, Slovakia, South Africa, South Korea, Spain, Taiwan, Thailand, Turkey (Türkiye), United Kingdom, United States
Outcome results
None listed