Phase 3 Randomized Double‑Blind Placebo‑Controlled Study of Oral Enpatoran in Adults With Active Cutaneous Lupus Erythematosus (with or without systemic disease)

The primary objective is to demonstrate the efficacy of enpatoran in reducing cutaneous disease activity by achieving at least a 70% reduction from baseline in CLASI-70 at week 24. Secondary objectives are to demonstrate overall disease activity improvement with a BICLA response at week 24; evaluate safety and tolerability; assess rapid onset of action defined as ≥50% reduction in CLASI-A total score (CLASI-50) at week 4; achieve low cutaneous disease activity or remission at week 24; reduce overall cutaneous disease activity; reduce systemic disease activity and corticosteroid use; and evaluate the effect on itch.

The trial enrolled 148 individuals, both male and female, aged 18 to 75 years, who were in generally stable health aside from active cutaneous lupus erythematosus. Participants were required to have a documented diagnosis of discoid lupus erythematosus, subacute cutaneous lupus erythematosus, or acute cutaneous lupus erythematosus, with or without systemic lupus erythematosus, and to meet the 2019 EULAR/ACR classification criteria when systemic disease was present. Inclusion criteria mandated a disease duration of at least six months, a baseline CLASI‑A score of ≥8, and up‑to‑date vaccinations per local guidelines; recombinant zoster vaccination was encouraged but not mandatory. Selection was based on these clinical and laboratory parameters, and no specific lifestyle restrictions such as diet or physical activity were stipulated in the protocol. The medical condition under investigation was Cutaneous Manifestations of Lupus Erythematosus.

The study is a Phase 3 randomized, double-blind, placebo-controlled parallel‑group trial evaluating oral Enpatoran versus matching placebo in adults with cutaneous lupus erythematosus (with or without systemic disease) who are receiving standard of care. After an eligibility screening visit, participants who meet all inclusion criteria undergo a baseline (Day 1) visit and are then assigned in a 1:1 ratio to receive either Enpatoran film‑coated tablets or placebo for a 24‑week treatment period. Scheduled study visits occur at weeks 4, 12, and 24 to assess efficacy, safety, laboratory parameters, and corticosteroid use; the week 24 visit serves as the end‑of‑study assessment. The primary endpoint is the proportion of participants achieving a ≥70 % reduction from baseline in the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI‑70) at Week 24, with secondary endpoints including BICLA response, adverse event incidence, grade ≥ 3 laboratory abnormalities, CLASI‑A ≤3, CLASI‑50 response at Weeks 4 and 24, and clinically meaningful corticosteroid reduction. Participant involvement spans approximately 24 weeks of active treatment plus the initial screening period.

The investigational product, Enpatoran, is supplied as a film‑coated tablet for oral administration. Each tablet contains enpatoran hemihydrate; the protocol specifies a dose of 0 mg per tablet, administered once daily throughout the 24‑week treatment period.

The control arm receives a matching placebo tablet identical in appearance to the active product. The placebo contains no active pharmaceutical ingredient and is taken orally once daily on the same schedule as the investigational drug.

Both study medications are dispensed in blister packs to facilitate blinded dosing. Participants are instructed to ingest the assigned tablet with water in the morning, preferably in a fasting state, and to refrain from eating for at least 30 minutes thereafter. Dosing compliance is assessed at each study visit by tablet count and patient diary review, with any missed doses documented and reported according to the trial’s monitoring procedures.

Efficacy will be evaluated primarily by the proportion of participants achieving a CLASI-70 response, defined as a ≥70 % reduction from baseline in the Cutaneous Lupus Erythematosus Disease Area and Severity Index activity score (CLASI‑A) at Week 24. The CLASI‑A is a validated clinician‑reported instrument that quantifies cutaneous disease activity and is administered at baseline and at the Week 24 visit.

Secondary efficacy assessments include: the proportion of participants attaining a BICLA response at Week 24; the proportion with a CLASI‑A score ≤3 at Week 24; the proportion achieving a CLASI-50 response (≥50 % reduction from baseline) at Weeks 4 and 24; and the proportion demonstrating a clinically meaningful corticosteroid reduction from Day 1 through Week 12 and continued through Week 24. These secondary endpoints are measured using the same CLASI‑A instrument and the British Isles Lupus Assessment Group Composite Lupus Assessment, with assessments scheduled at baseline, Week 4, Week 12, and Week 24. Data will be collected on standardized case report forms, entered into a secure database, and analyzed using predefined statistical methods to compare the enpatoran group with placebo.