Atopic Dermatitis
Conditions
Keywords
STAT6, stat6 degrader, targeted protein degrader, Phase 2, Phase 2b, kt-621
Brief summary
This phase 2b study is designed to evaluate the safety and efficacy of KT-621 in adult and adolescent participants with moderate-to-severe atopic dermatitis (AD), a common form of eczema. The main goals of this study are to learn how effective KT-621 is at reducing the severity and extent of AD, the safety and tolerability of KT-621, how KT-621 behaves in the body, and how the body responds to KT-621. This is a 16-week double-blind, placebo-controlled study with a 52-week open-label period.
Interventions
DRUGKT-621
Oral drug
OTHERPlacebo
Oral placebo matched to KT-621
Sponsors
Kymera Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
12 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Must be 12 to 75 years of age, inclusive, at the time of signing the IAF (informed assent form) and/or ICF (informed consent form). * Must have chronic AD that has been present for at least 3 years (for participants ≥ 18 years of age) or 1 year (for participants \< 18 years of age) before the Screening visit. * Must have an EASI score ≥ 16 at the Screening and Baseline visits. * Must have a vIGA-AD score ≥ 3 (scale of 0 to 4) at the Screening and Baseline visits. * Must have at least 10% BSA of AD involvement at the Screening and Baseline visits. * Must have a weekly average Peak Pruritus NRS value ≥ 4 at the Baseline visit. * Must have a history within the 6 months prior to the Baseline visit of either an inadequate response to, or inability to take, topical medications for the treatment of AD. * Must apply a stable dose of moisturizer at least twice daily for at least 7 consecutive days immediately prior to the Baseline visit. Participants should be willing to continue using moisturizer twice daily during the study. * Must be willing and able to comply with scheduled visits, treatment plan, laboratory tests, other study-related procedures, and questionnaires, including completing the electronic diary (e-diary), for the duration of the study as required by the study protocol. * Must agree to contraceptive requirements in compliance with the clinical study and local requirements.
Exclusion criteria
* Must not have an unstable course of AD (spontaneously improving or rapidly deteriorating) as determined by the Investigator in the 4 weeks before the baseline visit. * Must not have other skin conditions, such as contact dermatitis, psoriasis, tinea corporis, or lupus erythematosus, that may interfere with study assessments. * Must not have a clinically relevant history of respiratory, gastrointestinal (GI), renal, hepatic, hematological, lymphatic, endocrinological, neurological, cardiovascular, psychiatric, musculoskeletal, genitourinary, immunological, ophthalmological, or connective tissue diseases or disorders. * Must not have any surgical or medical procedure planned during participation in the study. * Must not have a history of alcohol or substance abuse within the previous 2 years. * Must not be pregnant or breastfeeding; must not be a woman planning to become pregnant or breastfeed during the study. * Must not have a history of lack of response to any medication targeting interleukin (IL)-4, IL-13, and/or janus kinase (JAK)- signal transducer and activator of transcription (STAT) pathways (e.g. dupilumab, tralokinumab, upadacitinib, abrocitinib) at approved doses after at least 16 weeks of therapy. * Must not have results from clinical laboratory safety tests that are outside the local reference range at Screening. * Must not have been dosed with any investigational drug or device in a clinical study within 8 weeks or 5 half-lives (whichever is longer) of KT-621 administration. * Female participants of childbearing potential must not have a positive or undetermined pregnancy result at the Screening and baseline visits. * Must not have any known factor, condition, or disease that might interfere with treatment compliance, study conduct or interpretation of the results. * Must not be taking or have taken any prespecified prohibited therapies within a specific timeframe as evaluated by the Investigator. * Must not have a known sensitivity to any of the components of KT-621. * Must not be a member of the investigational team or his/her immediate family.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change from baseline in Eczema Area and Severity Index (EASI) score | From baseline through Week 16 |
Secondary
| Measure | Time frame |
|---|---|
| Incidence of treatment-emergent adverse events (TEAEs) | From baseline through Week 16, and from Week 16 through Week 68 |
| Incidence of treatment-emergent serious adverse events (SAEs) | From baseline through Week 16, and from Week 16 through Week 68 |
| Percentage change from baseline in body surface area (BSA) affected by AD | From baseline to Week 16 and to Week 68 |
| Percentage change from baseline in the Peak Pruritus NRS score | From baseline to Week 16, and to Week 68 |
| Proportion of participants with at least a 4-point improvement from baseline in the Peak Pruritus Numerical Rating Scale (NRS) | At Week 16 and at Week 68 |
| Proportion of participants who achieve a validated Investigator Global Assessment Scale for Atopic Dermatitis (vIGA-AD) score of 0 to 1 (on a 5-point scale) and a reduction from the baseline value of at least 2 points | At Week 16 and at Week 68 |
| Proportion of participants with EASI-50, EASI-75, and EASI-90 | At Week 16 and at Week 68 |
| Percentage change from baseline in the EASI score | From baseline to Week 68 |
| Percentage change from baseline in the SCORing Atopic Dermatitis (SCORAD) score | From baseline to Week 16, and to Week 68 |
| Change from baseline in the Patient-Oriented Eczema Measure (POEM) | From baseline to Week 16, and to Week 68 |
| Change from baseline in the Dermatology Life Quality Index (DLQI) | From baseline to Week 16, and to Week 68 |
| Plasma concentration of KT-621 derived from plasma concentration time data | From baseline to Week 16, and to Week 68 |
Countries
Australia, Canada, Czechia, Germany, Japan, Poland, South Korea, United States
Outcome results
None listed