Clinical trial NCT06945458: Safety, PK, PD, and Clinical Activity of Orally Administered KT-621 in Adult Patients With Atopic Dermatitis (AD)
Official title: A Phase 1b Open-label, Multicenter, Single-arm Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Clinical Activity of Orally Administered KT-621 in Adult Participants With Moderate to Severe Atopic Dermatitis
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Atopic Dermatitis
Keywords: KT621
STAT6
STAT6 degrader
Targeted protein degrader
Phase 1
Lead sponsor: Kymera Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2025-04-25
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a study to evaluate safety, tolerability, pharmacokinetics, pharmacodynamics, and clinical activity of orally administered KT-621 in adult male and female patients with moderate to severe atopic dermatitis (AD).


Eligibility criteria: Inclusion Criteria:

* Participants aged 18 to 55 years (inclusive) at the time of screening
* Participants must be willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other procedures
* Participants must have had chronic atopic dermatitis (AD) for at least 1 year before Screening.
* Moderate to very severe eczema as determined by Eczema Area and Severity Index (EASI) score of at least 16 at the baseline visit.
* A validated Investigator Global Assessment (vIGA) score of at least 3 at the baseline visit, indicating moderate to severe AD.
* At least 10% body surface area (BSA) of AD involvement at the baseline visit.
* Weekly average Peak Pruritus Numeric Rating Scale (NRS) of at least 4 at the baseline visit.
* Documented history within 6 months prior to baseline visit of either inadequate response or contraindication to topical medications for AD.
* Application of stable dose of moisturizer at least twice daily for at least 7 consecutive days immediately prior to the baseline visit.

Exclusion Criteria:

* Participants who 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.
* Participants who have any surgical or medical procedure planned during participation in the study.
* Participants with a history of alcohol or substance abuse within the previous 2 years.
* Participants who have any known factor, condition, or disease that might interfere with treatment compliance, study conduct or interpretation of the results.
* Participants whose results from clinical laboratory safety tests are outside the local reference range at Screening.
* Participants who 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.
* Participants with 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.
* Pregnant or breastfeeding women, or women planning to become pregnant or breastfeed during the study.
* Female participants of childbearing potential with a positive or undetermined pregnancy result at the Screening and baseline visits.
* Participants with a known sensitivity to any of the components of KT-621.
* Participants who are a member of the investigational team or his/her immediate family.

Primary outcomes:
measure: Incidence of adverse events (AEs)
timeFrame: From enrollment through the safety follow-up visit on Day 43
measure: Incidence of treatment-emergent potentially clinically-significant abnormalities in electrocardiogram (ECG) results, vital signs, or laboratory test results from the serum chemistry, hematology (with differential), chemistry, or coagulation panels.
timeFrame: From enrollment through the safety follow-up visit on Day 43
Secondary outcomes:
measure: Plasma PK parameter estimates of KT-621 derived from plasma concentration-time data
timeFrame: From baseline visit through the safety follow-up visit on Day 43
Other outcomes:
measure: KT-621 concentrations in skin
timeFrame: From baseline visit through the safety follow-up visit on Day 43
measure: Change in Eczema Area and Severity Index (EASI) score
timeFrame: From screening through the safety follow-up visit on Day 43
measure: Proportion of participants who achieve a validated Investigator Global Assessment (vIGA) score of 0 or 1 at scheduled clinic visits
timeFrame: From screening through the safety follow-up visit on Day 43
measure: Change from baseline in the Peak Pruritus Numeric Rating Scale (NRS) score
timeFrame: From baseline visit through the safety follow-up visit on Day 43
measure: Change from baseline in levels of signal transducer and activator of transcription 6 protein, in skin and in whole blood
timeFrame: From baseline visit through the safety follow-up visit on Day 43
measure: Change from baseline in the serum levels of Th2 biomarkers such as thymus and activation-regulated chemokine (TARC)
timeFrame: From baseline visit through the safety follow-up visit on Day 43
measure: Change from baseline through Week 4 in the serum levels of proinflammatory cytokines
timeFrame: From baseline visit through the safety follow-up visit on Day 43
measure: Change from baseline through Week 4 in messenger RNA transcriptome levels on the skin.
timeFrame: From baseline visit through the safety follow-up visit on Day 43
Locations:
city: Birmingham
country: United States
facility: Kymera Investigative Site
state: Alabama
city: Fountain Valley
country: United States
facility: Kymera Investigative Site
state: California
city: Santa Monica
country: United States
facility: Kymera Investigative Site
state: California
city: Boynton Beach
country: United States
facility: Kymera Investigative Site
state: Florida
city: Hollywood
country: United States
facility: Kymera Investigative Site
state: Florida
city: Tampa
country: United States
facility: Kymera Investigative Site
state: Florida
city: Fargo
country: United States
facility: Kymera Investigative Site
state: North Dakota
city: Dublin
country: United States
facility: Kymera Investigative Site
state: Ohio
city: Springfield
country: United States
facility: Kymera Investigative Site
state: Ohio
city: Tulsa
country: United States
facility: Kymera Investigative Site
state: Oklahoma
city: Charleston
country: United States
facility: Kymera Investigative Site
state: South Carolina
city: San Antonio
country: United States
facility: Kymera Investigative Site
state: Texas
Study officials:
References: