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

The primary objective is to evaluate the efficacy of enpatoran in reducing cutaneous disease activity, defined as achieving at least a 70 % reduction from baseline in the Cutaneous Lupus Disease Area and Severity Index activity score (CLASI-70) at week 24. Demonstrating this magnitude of improvement would indicate a clinically meaningful attenuation of skin involvement in patients with cutaneous lupus erythematosus.

Secondary objectives include:

• Demonstration of overall disease control by attaining a BICLA response at week 24.
• Assessment of safety and tolerability of enpatoran throughout the study period.
• Evaluation of rapid onset of action, measured by achieving a 50 % reduction from baseline in CLASI-A score (CLASI-50) at week 4.
• Achievement of low cutaneous disease activity or remission at week 24.
• Overall reduction in cutaneous disease activity across time points.
• Reduction in systemic disease activity and concomitant corticosteroid use.
• Effect on patient‑reported itch severity.

The trial enrolled 145 participants aged 18 to 75 years, including both female and male individuals. Eligible subjects had documented diagnosis of discoid lupus erythematosus, subacute cutaneous lupus erythematosus, or acute cutaneous lupus erythematosus (as sole cutaneous manifestation in the presence of systemic lupus erythematosus) and met the 2019 EULAR/ACR classification criteria for systemic lupus erythematosus when applicable. All participants exhibited active cutaneous disease for at least six months and a baseline CLASI‑A score of ≥ 8. Vaccination status was required to be current according to local guidelines, with recombinant zoster vaccination encouraged but not mandatory. Both patients and vulnerable populations were considered for inclusion, provided they satisfied the disease‑specific criteria and general health requirements.

The study is a Phase 3, randomized, double-blind, placebo-controlled parallel‑group trial evaluating oral Enpatoran versus matching placebo in adults 18–75 years with active cutaneous lupus erythematosus. Participants undergo a screening visit to confirm eligibility, including diagnosis of DLE, SCLE, or ACLE and baseline CLASI‑A assessment; eligible subjects then enter a 24‑week treatment period with study visits at Day 1 (randomization), Weeks 4, 12, and 24 for efficacy and safety evaluations, followed by an end‑of‑study visit. The primary endpoint is the proportion achieving a CLASI‑70 response (≥70 % reduction from baseline) at Week 24. Secondary assessments include BICLA response, adverse event monitoring, laboratory safety, CLASI‑A ≤ 3, CLASI‑50 response, and corticosteroid reduction. Participant involvement therefore spans approximately 26 weeks including screening. Early termination may occur due to serious adverse events, Grade ≥ 3 laboratory abnormalities, significant protocol violations, or investigator discretion.

The investigational product is Enpatoran, supplied as a film‑coated tablet containing enpatoran hemihydrate. The medication is administered orally. The protocol specifies a dose of 0 mg per tablet, taken according to the dosing schedule defined in the study manual (e.g., once daily), with each dose taken at approximately the same time each day.

The control arm receives a matching Placebo tablet that is identical in appearance to the active film‑coated tablet. The placebo is also administered orally and follows the same dosing schedule and frequency as the active product to maintain blinding.

All participants continue to receive background standard of care therapy for cutaneous lupus erythematosus as prescribed by their treating physician. Concomitant medications are recorded at each visit, and any changes to the regimen are documented. Participant compliance with study medication is monitored by tablet count at each study visit and by patient diary entries documenting dosing times.

The primary efficacy assessment is the proportion of participants achieving a ≥70 % reduction from baseline in the Cutaneous Lupus Erythematosus Disease Area and Severity Index activity score at Week 24, defined as a CLASI‑70 response. The CLASI instrument, a validated clinical scoring system, will be administered at baseline and at the Week 24 visit to determine the change in score.

Secondary efficacy evaluations include the proportion of participants meeting a BICLA response at Week 24, the proportion with a CLASI activity score ≤3 at Week 24, the proportion achieving a ≥50 % reduction from baseline in the CLASI activity score at Weeks 4 and 24 (defined as a CLASI‑50 response), and the proportion demonstrating a clinically meaningful reduction in corticosteroid use from Day 1 to Week 12 and to Week 24. All secondary parameters are measured using the respective validated scales at the scheduled study visits.