Cutaneous Lupus Erythematosus (CLE)Phase 2/3DISCOVERYNCT07881120
Phase 2/3 Double-Blind, Placebo-Controlled Study of Afimetoran in Cutaneous Lupus Erythematosus
A Phase 2/3 study testing Afimetoran in people with Cutaneous Lupus Erythematosus (CLE) and Systematic Lupus Erythematosus, run by Beeline Medicines Corporation.
Trial summary
This study is evaluating whether afimetoran, an investigational oral medicine that blocks toll-like receptors 7 and 8 (TLR7/TLR8), can improve skin disease in adults with active cutaneous lupus erythematosus (CLE), with or without systemic lupus, whose disease has not responded to or who cannot tolerate antimalarial… Read more about this study
- Who is it for?
- Ages 16 years and older
- Conditions the study is for
- Cutaneous Lupus Erythematosus (CLE), Systematic Lupus Erythematosus
- What is being tested?
- Afimetoran
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 390 participants
- Where
- No sites listed yet
- Study dates
- Oct 2026to Apr 2031
- Phase
- Phase 2/3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Adults aged ≥18 years (or ≥16 years where permitted).
- Histologically confirmed active cutaneous lupus erythematosus (CLE) with or without systemic manifestations.
- Active subacute and/or chronic cutaneous lupus erythematosus, including discoid lupus erythematosus.
- Moderate to severe skin disease activity.
- Refractory, intolerant, or inadequately controlled on antimalarial therapy.
- Willing and able to comply with study requirements.
- Agreement to protocol-specified contraception requirements
Who cannot join
- Severe lupus nephritis or severe neuropsychiatric SLE
- Drug-induced lupus
- Active or chronic clinically significant infections, including HIV, hepatitis B, hepatitis C, active tuberculosis, untreated latent tuberculosis, or uncontrolled congestive heart failure
- Significant concurrent autoimmune disease other than lupus-related conditions permitted by the protocol
- Active malignancy or recent history of certain cancers
- Other dermatologic conditions that may interfere with study assessments
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- Recent use of prohibited medications or investigational therapies
- Prior treatment with afimetoran or another TLR7/TLR8 antagonist
- Clinically significant laboratory abnormalities or severe organ dysfunction
- Pregnancy or breastfeeding
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: A 2-Stage Operationally Seamless Phase 2/3, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Efficacy and Safety of Afimetoran in Participants With Active Cutaneous Lupus Erythematosus With or Without Systemic Manifestations and Refractory and/or Intolerant to Antimalarial Therapy
This study is evaluating whether afimetoran, an investigational oral medicine that blocks toll-like receptors 7 and 8 (TLR7/TLR8), can improve skin disease in adults with active cutaneous lupus erythematosus (CLE), with or without systemic lupus, whose disease has not responded to or who cannot tolerate antimalarial therapy. Participants are assigned by chance to receive afimetoran or a matching placebo capsule once daily for 24 weeks, in addition to their existing standard lupus care. Neither participants nor study staff know which treatment is given.
The study is run in two stages under a single protocol. Stage 1 compares two doses of afimetoran with placebo to select the dose. Stage 2 compares the selected afimetoran dose with placebo to confirm efficacy and safety. After the 24-week placebo-controlled period, all participants receive afimetoran for a further 28 weeks, for a total of 52 weeks of treatment. The main measures of benefit are the change in the CLASI-A skin activity score and the proportion of participants achieving a 70% improvement in that score at Week 24.
- Being tested
- Afimetoran, Placebo
- Keywords
- Subacute cutaneous lupus erythematosus (SCLE), Chronic cutaneous lupus erythematosus (CCLE), discoid lupus erythematosus (DLE), Afimetoran;, BLN-256;, BMS-986256;, TLR7/TLR8 antagonist, CLASI-A, antimalarial-refractory, Afimetoran, antimalarial-intolerant
- Medical subject headings
- Lupus Erythematosus, Cutaneous, Lupus Erythematosus, Discoid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AfimetoranDrug
Also called BLN-256
Afimetoran (BLN-256) oral capsule, once daily
PlaceboDrug
Placebo (capsule matched to afimetoran), once daily
| Study group | Role | What they receive |
|---|---|---|
| Afimetoran Dose 1 | Experimental | Not described Receives: Drug: Afimetoran |
| Afimetoran Dose 2 | Experimental | Not described Receives: Drug: Afimetoran |
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent change from baseline in CLASI-A total score
Demonstrates efficacy of afimetoran vs placebo based on CLASI-A change in participants with active CLE with or without systemic manifestations
Measured: Baseline to Week 24
Proportion of participants achieving a CLASI-70 response (≥70% decrease from baseline in CLASI-A total score)
To demonstrate the superiority of afimetoran compared with placebo based on CLASI-70 response in participants with active CLE with or without systemic manifestations
Measured: Week 24
Secondary outcomes (10)
Proportion achieving CLASI-70 response, CLASI-50 response, and CLASI-A total score of 0-3; percent and absolute change from baseline in CLASI-A total score; time to first and sustained response
Efficacy of afimetoran vs placebo in reducing skin disease activity
Measured: Weeks 12, 16, and 24 (time-to-event up to Week 24)
Proportion of Participants Achieving a Cutaneous Lupus Activity-Investigator's Global Assessment-Revised (CLA-IGA-R) Erythema Score of 0 or 1
Proportion of participants achieving a CLA-IGA-R Erythema score of 0 (clear) or 1 (almost clear). Scores range from 0 to 4, with lower scores indicating less disease activity.
Measured: Weeks 12, 16, and Week 24
Proportion of Participants Achieving a CLA-IGA-R Mucous Membrane, Edema, and Scale/Hypertrophy (OMC) Score of 0 or 1
Proportion of participants achieving a CLA-IGA-R OMC score of 0 (clear) or 1 (almost clear). Scores range from 0 to 4, with lower scores indicating less disease activity
Measured: Weeks 12, 16, and Week 24
Change From Baseline in Patient Global Assessment of Skin Disease Activity (PtGA-Skin Disease Activity)
Change from baseline in PtGA-Skin Disease Activity score. The assessment uses a numeric rating scale ranging from 0 to 10. Higher scores indicate greater disease activity and worse symptoms.
Measured: Weeks 12, 16, 24, and 52
Change From Baseline in Cutaneous Lupus Erythematosus Quality of Life (CLE-QoL) Total Score
Change from baseline in CLE-QoL total score. Higher scores indicate greater impairment in quality of life associated with cutaneous lupus erythematosus.
Measured: Weeks 12, 16, 24, and 52
Change From Baseline in Dermatology Life Quality Index (DLQI) Total Score
Change from baseline in DLQI total score. Scores range from 0 to 30, with higher scores indicating greater impairment in quality of life.
Measured: Weeks 12, 16, 24, and 52
Proportion of Participants Achieving a ≥4-Point Reduction From Baseline in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K)
Proportion of participants with SLE at baseline achieving a reduction of at least 4 points from baseline in SLEDAI-2K score without change in lupus standard-of-care therapy and/or increase in oral corticosteroid dose. SLEDAI-2K scores range from 0 to 105, with higher scores indicating greater disease activity.
Measured: Weeks 24 and 52
Proportion of Participants With SLE at Baseline Achieving Lupus Low Disease Activity State (LLDAS)
Proportion of participants with SLE at baseline achieving LLDAS
Measured: Weeks 24 and 52
Incidence of Treatment-Emergent Adverse Events (TEAEs)
Number of participants experiencing at least one treatment-emergent adverse event.
Measured: Up to 52 Weeks
Incidence of Serious Adverse Events (SAEs)
Number of participants experiencing at least one serious adverse event.
Measured: Up to 52 Weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Oct 2026
- Study startOct 2026 (estimated)
- Primary completionApr 2030 (estimated)
- Study completionApr 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cutaneous Lupus Erythematosus (CLE)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 390 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Beeline Medicines Corporation
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Study Director, Study director, Beeline Medicines Corporation
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07881120
- Sponsor's protocol ID
- AFI-CLE-201
- Other IDs
- 2026-528004-34-00
- Acronym
- DISCOVERY
- Status last verified
- Oct 2026
- First submitted
- 5 Oct 2026
- Last updated
- 19 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided: No internal process at this time
Study at a glance
From the registry record, last updated by the sponsor on 19 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A 2-Stage Operationally Seamless Phase 2/3, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Efficacy and Safety of Afimetoran in Participants With Active Cutaneous Lupus Erythematosus With or Without Systemic Manifestations and Refractory and/or Intolerant to Antimalarial Therapy
- ClinicalTrials.gov ID
- NCT07881120
- Acronym / sponsor ID
- DISCOVERY / AFI-CLE-201
- Keywords
- Subacute cutaneous lupus erythematosus (SCLE), Chronic cutaneous lupus erythematosus (CCLE), discoid lupus erythematosus (DLE), Afimetoran;, BLN-256;, BMS-986256;, TLR7/TLR8 antagonist, CLASI-A
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 390 participants (estimated)
- Lead sponsor
- Beeline Medicines CorporationIndustry (pharma, biotech, devices)
- Study start
- Oct 2026 (estimated)
- Primary completion
- Apr 2030 (estimated)
- Study completion
- Apr 2031 (estimated)
- First posted
- 19 Oct 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is evaluating whether afimetoran, an investigational oral medicine that blocks toll-like receptors 7 and 8 (TLR7/TLR8), can improve skin disease in adults with active cutaneous lupus erythematosus (CLE), with or without systemic lupus, whose disease has not responded to or who cannot tolerate antimalarial therapy. Participants are assigned by chance to receive afimetoran or a matching placebo capsule once daily for 24 weeks, in addition to their existing standard lupus care. Neither participants nor study staff know which treatment is given.
The study is run in two stages under a single protocol. Stage 1 compares two doses of afimetoran with placebo to select the dose. Stage 2 compares the selected afimetoran dose with placebo to confirm efficacy and safety. After the 24-week placebo-controlled period, all participants receive afimetoran for a further 28 weeks, for a total of 52 weeks of treatment. The main measures of benefit are the change in the CLASI-A skin activity score and the proportion of participants achieving a 70% improvement in that score at Week 24.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Afimetoran Dose 1 | Experimental | Drug: Afimetoran |
| Afimetoran Dose 2 | Experimental | Drug: Afimetoran |
| Placebo | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 16 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (7 listed)
- Adults aged ≥18 years (or ≥16 years where permitted).
- Histologically confirmed active cutaneous lupus erythematosus (CLE) with or without systemic manifestations.
- Active subacute and/or chronic cutaneous lupus erythematosus, including discoid lupus erythematosus.
- Moderate to severe skin disease activity.
- Refractory, intolerant, or inadequately controlled on antimalarial therapy.
Key exclusion criteria (10 listed)
- Severe lupus nephritis or severe neuropsychiatric SLE
- Drug-induced lupus
- Active or chronic clinically significant infections, including HIV, hepatitis B, hepatitis C, active tuberculosis, untreated latent tuberculosis, or uncontrolled congestive heart failure
- Significant concurrent autoimmune disease other than lupus-related conditions permitted by the protocol
- Active malignancy or recent history of certain cancers
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AfimetoranAlso: BLN-256Afimetoran (BLN-256) oral capsule, once daily | Drug | Afimetoran Dose 1, Afimetoran Dose 2 |
| PlaceboPlacebo (capsule matched to afimetoran), once daily | Drug | Placebo |
Primary outcome
Percent change from baseline in CLASI-A total score
Time frame: Baseline to Week 24
Demonstrates efficacy of afimetoran vs placebo based on CLASI-A change in participants with active CLE with or without systemic manifestations
Proportion of participants achieving a CLASI-70 response (≥70% decrease from baseline in CLASI-A total score)
Time frame: Week 24
To demonstrate the superiority of afimetoran compared with placebo based on CLASI-70 response in participants with active CLE with or without systemic manifestations
10 secondary outcomes
Proportion achieving CLASI-70 response, CLASI-50 response, and CLASI-A total score of 0-3; percent and absolute change from baseline in CLASI-A total score; time to first and sustained response
Time frame: Weeks 12, 16, and 24 (time-to-event up to Week 24)
Proportion of Participants Achieving a Cutaneous Lupus Activity-Investigator's Global Assessment-Revised (CLA-IGA-R) Erythema Score of 0 or 1
Time frame: Weeks 12, 16, and Week 24
Proportion of Participants Achieving a CLA-IGA-R Mucous Membrane, Edema, and Scale/Hypertrophy (OMC) Score of 0 or 1
Time frame: Weeks 12, 16, and Week 24
Change From Baseline in Patient Global Assessment of Skin Disease Activity (PtGA-Skin Disease Activity)
Time frame: Weeks 12, 16, 24, and 52
Change From Baseline in Cutaneous Lupus Erythematosus Quality of Life (CLE-QoL) Total Score
Time frame: Weeks 12, 16, 24, and 52
Change From Baseline in Dermatology Life Quality Index (DLQI) Total Score
Time frame: Weeks 12, 16, 24, and 52
Proportion of Participants Achieving a ≥4-Point Reduction From Baseline in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K)
Time frame: Weeks 24 and 52
Proportion of Participants With SLE at Baseline Achieving Lupus Low Disease Activity State (LLDAS)
Time frame: Weeks 24 and 52
Incidence of Treatment-Emergent Adverse Events (TEAEs)
Time frame: Up to 52 Weeks
Incidence of Serious Adverse Events (SAEs)
Time frame: Up to 52 Weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Oct 2026.
- Individual participant dataSharing planned: Undecided. No internal process at this time
Related trials for Cutaneous Lupus Erythematosus (CLE)
Active, not recruitingPhase 2/3
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Subacute Cutaneous Lupus Erythematosus, Chronic Cutaneous Lupus Erythematosus
Active, not recruitingPhase 2
The Willow LTE Study With M5049 in Participants With SCLE, DLE and/or SLE (WILLOW LTE)
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RecruitingPhase 3
A Study of Enpatoran in Participants With Cutaneous Manifestations of Lupus With or Without Systemic Disease
Systemic Lupus Erythematosus (SLE), Cutaneous Lupus Erythematosus (CLE)
RecruitingPhase 3
A Study of Enpatoran in Participants With Cutaneous Manifestations of Lupus With or Without Systemic Disease (ELOWEN-2)
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RecruitingPhase 2
A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase 2a Study With an Open-Label Extension Evaluating the Efficacy and Safety of VENT-03 in Adult Participants With Active Cutaneous Lupus Erythematosus With or Without Systemic Lupus Erythematosus
Cutaneous Lupus Erythematosus (CLE), Systemic Lupus Erythematosus
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Study Director study director
Beeline Medicines Corporation
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Afimetoran in people with Cutaneous Lupus Erythematosus (CLE) and Systematic Lupus Erythematosus, run by Beeline Medicines Corporation.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 19 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Study Director (1 617 885-8290, medinfo@beelinemedicines.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percent change from baseline in CLASI-A total score (time frame: Baseline to Week 24). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Oct 2026.