A 2-stage, Phase III Study to Investigate the Efficacy and Safety of Anifrolumab in Adults With Chronic and/or Subacute Cutaneous Lupus Erythematosus (LAVENDER)
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The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT06015737 |
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Recruitment Status :
Not yet recruiting
First Posted : August 29, 2023
Last Update Posted : April 23, 2024
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Sponsor:
AstraZeneca
Collaborator:
Parexel
Information provided by (Responsible Party):
AstraZeneca
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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).
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Cutaneous Lupus Erythematosus | Combination Product: Anifrolumab Other: Placebo | Phase 3 |
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.
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 460 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Intervention Model Description: | This is a parallel group treatment study in two concurrent stages (Stage 1 and Stage 2) and each stage will have two arms. |
| Masking: | Double (Participant, Investigator) |
| Primary Purpose: | Treatment |
| 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 |
| Estimated Study Start Date : | May 9, 2024 |
| Estimated Primary Completion Date : | December 21, 2027 |
| Estimated Study Completion Date : | December 21, 2027 |
Resource links provided by the National Library of Medicine
Drug Information
available for:
Anifrolumab
| Arm | Intervention/treatment |
|---|---|
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Experimental: Stage 1: Anifrolumab
The participants will receive anifrolumab as a SC injection from Week 0/Day 1 up to and including week 51.
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Combination Product: Anifrolumab
Anifrolumab will be provided as a solution for injection in accessorized pre-filled syringe (aPFS). |
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Placebo Comparator: Stage 1: 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.
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Other: Placebo
Matching placebo solution for injection in aPFS. |
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Experimental: Stage 2: Anifrolumab
The participants will receive anifrolumab as a SC injection from Week 0/Day 1 up to and including week 51.
|
Combination Product: Anifrolumab
Anifrolumab will be provided as a solution for injection in accessorized pre-filled syringe (aPFS). |
|
Placebo Comparator: Stage 2: 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.
|
Other: Placebo
Matching placebo solution for injection in aPFS. |
Primary Outcome Measures :
- 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 [ Time Frame: 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 [ Time Frame: 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 :
- 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 [ Time Frame: 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 who achieve a CLA-IGA-R OMC score of 0. [ Time Frame: 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 follicular activity score of 0 [ Time Frame: 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 [ Time Frame: 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): Percent change from baseline in total CLASI-A scale/hypertrophy score [ Time Frame: 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, or a CLA-IGA-R OMC score of 0 or 1 and at least a 1-point reduction relative to baseline [ Time Frame: 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): Number of participants with CLA-IGA-R erythema score of 0 or 1 and at least a 2-point reduction relative to baseline [ Time Frame: 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): Number of participants with CLA-IGA-R OMC score of 0 or 1 and at least a 1-point reduction relative to baseline [ Time Frame: 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 (EU/ROW): Number of participants with CLASI-70 response [ Time Frame: 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/EU/ROW): Change from baseline in Skindex-29+3 domain scores [ Time Frame: 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): Serum trough (pre-dose) concentrations of anifrolumab [ 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) ]The Ctrough of subcutaneously administered anifrolumab in participants with chronic and/or subacute CLE will be evaluated.
- Stage 1 and Stage 2 (US/EU/ROW): Number of participants with positive antidrug antibody [ 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) ]The immunogenicity of subcutaneously administered anifrolumab in participants with chronic and/or subacute CLE will be evaluated.
- Stage 1 and Stage 2 (US/EU/ROW): Percent change from baseline in suppression of the Interferon 21-gene [ 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) ]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 [ Time Frame: 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 [ Time Frame: 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.
- Stage 2 (EU): Number of participants who are CLASI-70 responders up to and including Week 52 [ Time Frame: 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.
Other Outcome Measures:
- Stage 1 and Stage 2 (US, EU and ROW): Number of participants with adverse events [ Time Frame: Screening (up to and including 42 days before Day 1) until Safety Follow-up Period (13 weeks from Week 52/ EDV) ]To evaluate the safety and tolerability of anifrolumab compared with placebo in participants with CLE.
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Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years to 70 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Key inclusion criteria:
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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
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT06015737
Contacts
| Contact: AstraZeneca Clinical Study Information Center | 1-877-240-9479 | information.center@astrazeneca.com |
Locations
Show 69 study locations
Sponsors and Collaborators
AstraZeneca
Parexel
| Responsible Party: | AstraZeneca |
| ClinicalTrials.gov Identifier: | NCT06015737 |
| Other Study ID Numbers: |
D346BC00001 2021-003698-70 ( EudraCT Number ) |
| First Posted: | August 29, 2023 Key Record Dates |
| Last Update Posted: | April 23, 2024 |
| Last Verified: | April 2024 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| 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. |
| Supporting Materials: |
Study Protocol Statistical Analysis Plan (SAP) |
| 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. |
| 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. |
| URL: | https://vivli.org/ |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by AstraZeneca:
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Lupus erythematosus Cutaneous lupus erythematosus Anifrolumab Cutaneous Lupus Erythematosus Disease Area Severity Index Cutaneous lupus activity - Investigator's Global Assessment - Revised |
Additional relevant MeSH terms:
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Lupus Erythematosus, Systemic Lupus Erythematosus, Cutaneous Connective Tissue Diseases Autoimmune Diseases Immune System Diseases |
Skin Diseases Antibodies, Monoclonal Immunologic Factors Physiological Effects of Drugs |