Efficacy and Safety of Lebrikizumab in Adults With Moderate to Severe Localized Scleroderma: Randomized, Double-Blind, Placebo-Controlled Trial

Primary objective: to assess the efficacy of subcutaneous lebrikizumab 250 mg administered every two weeks versus placebo in adult patients with moderate to severe localized scleroderma after 24 weeks, thereby determining its potential to modify disease activity. Secondary objectives:

• to evaluate the impact of lebrikizumab on health‑related quality of life and overall disease activity;
• to assess safety and tolerability relative to placebo;
• to characterize the peripheral T‑cell profile;
• to characterize local inflammation and sclerosis in affected skin areas.

The trial enrolled adult participants of both sexes diagnosed with Localized Scleroderma meeting specific disease activity criteria; all subjects were required to be ≥18 years old, to have a baseline mLoSSI score of at least 5, and to exhibit plaque‑type or generalized disease with documented lesion enlargement or erythema within the preceding six months and at least one active lesion. Enrollment required documented insufficient response to potent topical steroid therapy for more than three months and acquisition of a signed, dated informed consent prior to any protocol‑related procedures. The sponsor did not provide information on the total number of participants enrolled. Subjects were selected based on these clinical and diagnostic parameters; no additional lifestyle restrictions such as diet or physical activity were stipulated in the available description.

A multicenter, randomized, double‑blind, placebo‑controlled Phase 4 trial will assess the efficacy and safety of 250 mg subcutaneous lebrikizumab administered every two weeks versus a matching placebo in adult patients with moderate to severe Localized Scleroderma. Recruitment is scheduled to commence 30 April 2026 and conclude 31 March 2028. After obtaining written informed consent, eligible participants undergo a screening visit to confirm diagnosis, baseline mLoSSI ≥5, and prior inadequate response to potent topical steroids. Participants then enter a 24‑week treatment period with study visits at week 0 (baseline), week 2, 4, 8, 12, 16, 20, and 24 for drug administration, safety assessments, and efficacy evaluations, followed by an end‑of‑study visit at week 28 to capture post‑treatment outcomes. The overall participant involvement spans approximately 28 weeks, including screening and follow‑up. Randomization is performed centrally in a 1:1 ratio, and both investigators and subjects remain blinded to treatment allocation. Early termination may occur due to serious adverse events, lack of adherence to the dosing schedule, withdrawal of consent, or clinically significant disease progression that warrants alternative therapy. The primary endpoint is the absolute change from baseline in mLoSSI score at week 24.

The investigational product, Ebglyss 250 mg solution for injection in a pre‑filled syringe, contains the monoclonal antibody lebrikizumab. It is supplied as a sterile solution for injection and is administered by subcutaneous injection. Each dose delivers 250 mg of active substance and is given once every two weeks (Q2W) for a total treatment period of 24 weeks. Dosing is performed in a clinical setting, and adherence is monitored through injection‑site logs, electronic case report forms, and periodic compliance checks by study staff.

The comparator is a matching placebo to the investigational medicinal product. The placebo has no active pharmaceutical ingredients and is provided in an identical pre‑filled syringe to maintain blinding. It is administered subcutaneously using the same schedule as the active treatment (every two weeks for 24 weeks). Compliance monitoring for the placebo follows the same procedures as for the active arm.

Both study arms receive standard supportive care as required for the underlying condition, localized scleroderma. Concomitant medications are recorded, and any deviations from the dosing schedule are documented in the trial database.

The primary efficacy assessment will be based on the mLoSSI score measured at baseline and after 24 weeks of treatment. Absolute change from the baseline visit in the mLoSSI score will be compared between the lebrikizumab and placebo groups.

Efficacy data will be collected using the validated Modified Localized Scleroderma Skin Severity Index instrument at the specified timepoints. Statistical analysis will evaluate the between‑group difference in the change from baseline to week 24.