A 2-stage, Phase III Study to Investigate the Efficacy and Safety of Anifrolumab in Adults With Chronic and/or Subacute Cutaneous Lupus Erythematosus
- Conditions
- Cutaneous Lupus Erythematosus
- Interventions
- Combination Product: AnifrolumabOther: Placebo
- Registration Number
- NCT06015737
- Lead Sponsor
- AstraZeneca
- Brief Summary
This study aims to evaluate the efficacy and safety of subcutaneous (SC) anifrolumab versus placebo in adult participants with cutaneous lupus erythematosus (CLE).
- Detailed 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 & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 460
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Stage 1: Anifrolumab Anifrolumab The participants will receive anifrolumab as a SC injection from Week 0/Day 1 up to and including week 51. Stage 1: Placebo Placebo The participant will receive placebo as a SC injection from Week 0/Day 1 to Week 23. From Week 24 the participants will receive anifrolumab up to and including Week 51. Stage 2: Anifrolumab Anifrolumab The participants will receive anifrolumab as a SC injection from Week 0/Day 1 up to and including week 51. Stage 2: Placebo Placebo The participant will receive placebo as a SC injection from Week 0/Day 1 to Week 23. From Week 24 the participants will receive anifrolumab up to and including Week 51.
- Primary Outcome Measures
Name Time Method 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 At Week 24 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.
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 At Week 24 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.
- Secondary Outcome Measures
Name Time Method 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 At Week 24 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.
Stage 1 and Stage 2 (US/EU/ROW): 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.
Stage 2 (EU): Number of participants who are CLASI-70 responders up to and including Week 52 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 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.
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 At Week 24 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.
Stage 1 and Stage 2 (US): Number of participants with CLA-IGA-R follicular activity score of 0 At Week 24 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.Stage 1 and Stage 2 (EU/ROW): Percent change from baseline in total CLASI-A erythema score At Week 24 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
Stage 1 and Stage 2 (EU/ROW): 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.
Stage 1 and Stage 2 (US): Number of participants who achieve a CLA-IGA-R OMC score of 0. At Week 24 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.
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 At Week 12 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.
Stage 1 and Stage 2 (US/EU/ROW): 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.
Stage 1 and Stage 2 (EU/ROW): Percent change from baseline in total CLASI-A scale/hypertrophy score At Week 24 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.
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 At Week 12 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.
Stage 1 and Stage 2 (US/EU/ROW): Change from baseline in Skindex-29+3 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. 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.
Stage 1 and Stage 2 (US/EU/ROW): 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.
Stage 2 (US/EU/ROW): Number of participants with ≥ 7-point reduction from baseline in CLASI-A total 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. 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.
Stage 2 (US): Number of participants who are CLA-IGA-R erythema responders from Week 24 up to and including Week 52 Up to 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.
Trial Locations
- Locations (1)
Research Site
🇬🇧Newcastle upon Tyne, United Kingdom