Efficacy and Safety Evaluation of Rezpegaldesleukin in Severe to Very Severe Alopecia Areata: A Phase 2B Randomized, Double-Blind, Placebo-Controlled Study

The primary objective of this study is to compare the **efficacy** of rezpegaldesleukin versus placebo in reducing hair loss at Week 36 in patients with severe to very severe **Alopecia Areata**. This is clinically relevant as it aims to address a significant unmet need in the management of this condition, potentially offering a new therapeutic option for patients with limited treatment choices.

Secondary objectives include:

• Comparing the efficacy of rezpegaldesleukin versus placebo on reducing hair loss in patients with severe to very severe Alopecia Areata.

The clinical trial involves a total of **46 participants** diagnosed with **Alopecia Areata**, specifically targeting individuals with severe to very severe cases. The study population includes both male and female adults, with an age range of 18 to 60 years for males and up to 70 years for females. Participants were selected based on their diagnosis of severe to very severe Alopecia Areata, characterized by at least 50% scalp involvement, and a documented history of the condition persisting for over six months without spontaneous improvement. The trial includes individuals who are able to complete patient questionnaires, comply with study visits and procedures, and provide written informed consent. Both genders are represented, and the study considers vulnerable populations. Participants' lifestyle factors such as diet, physical activity, or habits are not specified in the available data. Key inclusion criteria include the ability to communicate, read, and understand the local language, and for women of childbearing potential, a negative pregnancy test is required at screening and baseline, along with the use of approved contraceptive methods during the study and for at least 30 days after the last dose of the investigational product.

The clinical trial is a **randomized**, **double-blind**, parallel-group, placebo-controlled study designed to evaluate the efficacy and safety of **rezpegaldesleukin** in the treatment of severe to very severe **alopecia areata** in adult patients. The trial aims to compare the efficacy of rezpegaldesleukin versus placebo in reducing hair loss at Week 36, with the primary endpoint being the percent change from baseline in the Severity of Alopecia Tool (SALT) score. Secondary endpoints include the percent change in SALT score at various intervals and the proportion of patients achieving significant improvement in their SALT scores.

The trial is expected to commence recruitment on November 29, 2024, and conclude by August 24, 2026. Participants will be involved in the study for a maximum treatment period of 52 weeks. The study will include an initial screening visit to confirm eligibility based on criteria such as age, diagnosis of alopecia areata, and ability to comply with study procedures. Following the screening, eligible participants will be randomized to receive either the investigational product, rezpegaldesleukin, administered as a **solution for injection** via **subcutaneous injection**, or a placebo.

Study visits will occur at regular intervals to monitor the participants' progress and collect data on the primary and secondary endpoints. These visits will include assessments of the SALT score at Weeks 12, 16, 20, 24, 28, 32, and 36. The end-of-study visit will mark the completion of the trial for each participant, where final assessments will be conducted. Participants may be withdrawn from the study early if they experience adverse events, fail to comply with study procedures, or withdraw consent.

The clinical trial involves the administration of **NKTR-358**, a PEGylated form of recombinant human interleukin (IL)-2, known by its active substance name **rezpegaldesleukin**. This experimental medication is provided in the form of a **solution for injection**. The route of administration is via **subcutaneous injection**. The trial is designed to evaluate the efficacy and safety of rezpegaldesleukin in the treatment of severe to very severe **alopecia areata** in adult patients. The dosing schedule and frequency of administration are not explicitly detailed in the provided data, but the maximum treatment period is specified as 52 weeks. Participant compliance with the dosing regimen will be monitored throughout the study.

In addition to the experimental treatment, a **placebo** is utilized as a comparator in this double-blind, placebo-controlled study. The placebo is administered in a manner consistent with the experimental treatment to maintain the study's blinding. The pharmaceutical form, dosage, and route of administration for the placebo are not specified in the provided data. The use of a placebo is critical in assessing the true efficacy of the experimental medication by providing a baseline for comparison. Compliance with the placebo administration will also be monitored to ensure the integrity of the trial results.

The efficacy of the investigational product, **rezpegaldesleukin**, will be assessed in a Phase 2B, randomized, double-blind, parallel group, placebo-controlled clinical trial. The primary endpoint for evaluating efficacy is the percent change from baseline in the Severity of Alopecia Tool (SALT) score at Week 36. Secondary endpoints include the percent change from baseline in SALT score at Weeks 12, 16, 20, 24, 28, and 32, as well as the proportion of patients achieving improvement in SALT scores of 50%, 75%, and 90% (SALT50, SALT75, and SALT90) relative to their baseline score at Weeks 12, 16, 20, 24, 28, 32, and 36. Additionally, the proportion of patients achieving an absolute SALT score of 10, 20, 30, and 50 relative to their baseline score at the same timepoints will be evaluated.

The SALT score, a validated scale, will be used to measure the severity of **alopecia areata** in patients, with assessments conducted at specified intervals throughout the study. Data collection will occur at baseline and at multiple timepoints, specifically Weeks 12, 16, 20, 24, 28, 32, and 36, to monitor changes in hair loss severity. The analysis will focus on comparing the efficacy of rezpegaldesleukin against placebo in reducing hair loss in patients with severe to very severe alopecia areata. The study aims to provide comprehensive insights into the therapeutic potential of rezpegaldesleukin in this patient population.