A Phase 2b, Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicenter, Dose-ranging Study With an Open-label Period Investigating the Efficacy and Safety Profile of KT-621 Administered Orally to Participants with Moderate to Severe Atopic Dermatitis

The primary objective of this study is to evaluate the efficacy of multiple KT-621 doses compared with placebo in participants with moderate to severe atopic dermatitis. This assessment is clinically relevant for determining the therapeutic benefit of KT-621 in reducing disease severity and improving clinical outcomes in this patient population.

The secondary objectives include:

• To evaluate the safety and tolerability of multiple doses of KT-621 compared with placebo treatment in participants with moderate to severe atopic dermatitis.

• To evaluate the long-term efficacy of KT-621 treatment in participants with moderate to severe atopic dermatitis.

• To evaluate the long-term safety of KT-621 treatment in participants with moderate to severe atopic dermatitis.

• To characterize the pharmacokinetics of KT-621 in blood in participants with moderate to severe atopic dermatitis.

This clinical trial enrolled a total of **92 participants** diagnosed with **moderate to severe atopic dermatitis**. The study population included both **male and female subjects** aged **18 to 75 years**. Participants were required to have **chronic atopic dermatitis** present for at least 3 years prior to enrollment. Key selection criteria included an **EASI score** of 16 or higher, a **vIGA-AD score** of 3 or greater on a scale of 0 to 4, and at least **10% body surface area involvement** at both screening and baseline visits. Additionally, participants demonstrated a **weekly average Peak Pruritus NRS** of 4 or higher at baseline, indicating significant pruritus severity. Eligible individuals had a documented history within 6 months prior to baseline of either inadequate response to or contraindication to **topical medications** for atopic dermatitis treatment. Lifestyle considerations included the requirement for participants to apply a stable dose of **moisturizer** at least twice daily for a minimum of 7 consecutive days immediately before the baseline visit. The trial population included vulnerable populations as defined by regulatory standards.

This is a Phase 2b, randomized, double-blind, placebo-controlled, parallel-group, multicenter, dose-ranging study with an open-label period. The trial investigates the efficacy and safety profile of KT-621 administered orally to participants with moderate to severe atopic dermatitis. The study design includes a double-blind, placebo-controlled treatment period during which participants are randomly assigned to receive either KT-621 or a matching placebo. The placebo is designed to match the study drug in appearance and administration method to maintain blinding. KT-621 is formulated as a tablet for oral use with a maximum treatment period of 68 weeks.

The primary objective is to evaluate the efficacy of multiple KT-621 doses compared with placebo in participants with moderate to severe atopic dermatitis. The primary endpoint is the percentage change from baseline to Week 16 in the EASI score. Secondary endpoints include the proportion of participants achieving EASI-50, EASI-75, and EASI-90 at Week 16, the proportion of participants who achieve a vIGA-AD score of 0 to 1 with a reduction from baseline of at least 2 points at Week 16, and the proportion of participants with at least a 4-point improvement in the Peak Pruritus NRS at Week 16. Additional secondary endpoints include the incidence of treatment-emergent adverse events and treatment-emergent serious adverse events through Week 16 and from Week 16 through Week 68, as well as plasma pharmacokinetic parameter estimates of KT-621.

Principal inclusion criteria require participants to be 18 to 75 years of age at the time of signing the informed consent form. Participants must have chronic atopic dermatitis that has been present for at least 3 years before the screening visit. At both the screening and baseline visits, participants must have an EASI score of 16 or greater, a vIGA-AD score of 3 or greater on a scale of 0 to 4, and at least 10% body surface area involvement of atopic dermatitis. A weekly average Peak Pruritus NRS of 4 or greater at the baseline visit is required. Participants must have a documented history within the 6 months prior to the baseline visit of either an inadequate response to or contraindication to topical medications for the treatment of atopic dermatitis. Application of a stable dose of moisturizer at least twice daily for at least 7 consecutive days immediately prior to the baseline visit is also required.

The study is expected to commence recruitment on March 30, 2026, with an estimated end date of June 30, 2028. The overall trial duration extends up to 68 weeks. Participant involvement includes the screening visit for eligibility assessment, the baseline visit for randomization and treatment initiation, regular follow-up visits through Week 16 during the double-blind treatment period, and continued follow-up through Week 68 during the open-label period. The end-of-study visit occurs at Week 68 or upon early termination.

The experimental medication under investigation is KT-621, a chemical substance administered in tablet form via the oral route. The study evaluates multiple dose levels of KT-621 in participants with moderate to severe atopic dermatitis. The maximum treatment period for KT-621 administration is 68 weeks. The tablets are manufactured by KYMERA THERAPEUTICS, INC. and contain KT-621 as the active substance. The study design incorporates a dose-ranging approach to assess the efficacy and safety profile of different KT-621 dosages compared to placebo.

A matching placebo is utilized during the double-blind, placebo-controlled treatment period. Participants are randomly assigned to receive either KT-621 or the matching placebo in a parallel-group design. The placebo is specifically designed to match the study drug in appearance and administration method to maintain blinding throughout the controlled treatment phase. This ensures that neither participants nor investigators can distinguish between active treatment and placebo based on physical characteristics or method of administration, thereby preserving the integrity of the double-blind study design.

Efficacy will be assessed through multiple parameters evaluating clinical improvement in atopic dermatitis. The primary efficacy endpoint is the percentage change from baseline to Week 16 in the EASI score. Secondary efficacy endpoints include the proportion of participants achieving EASI-50, EASI-75, and EASI-90 at Week 16, which represent 50%, 75%, and 90% improvement in the EASI score, respectively. Additional secondary endpoints assess the proportion of participants who achieve a vIGA-AD score of 0 to 1 on a 5-point scale with a reduction from baseline of at least 2 points at Week 16, and the proportion of participants with at least a 4-point improvement in the Peak Pruritus NRS at Week 16. Efficacy assessments will be conducted at specified timepoints, with the primary evaluation occurring at Week 16 and extended evaluations continuing through Week 68 during the open-label period.