KT-474 is an oral heterobifunctional small molecule IRAK4 degrader being developed for the treatment of interleukin-1 receptor (IL-1R)/toll-like receptor (TLR)-driven immune-inflammatory diseases. This first-in-human (FIH) study will characterize the safety, tolerability and the pharmacokinetics/pharmacodynamics (PK/PD) of a single ascending dose and multiple ascending doses of KT-474 in healthy volunteers and patients with atopic dermatitis (AD) or hidradenitis suppurativa (HS). The effects of food on the absorption of KT-474 will also be evaluated in healthy volunteers.
This is a first-in-human (FIH), Phase 1 randomized, placebo-controlled, single and multiple ascending dose trial of KT-474 that will characterize the safety, PK and PD of orally administered KT-474 after a single dose (Part A) and after repeated dosing first in healthy adult volunteers (Part B) and then in patients with AD or HS (Part C). Initially, a dose range of KT-474 in single ascending dose (SAD) escalation cohorts will be explored in healthy subjects. Up to five single dose cohorts of healthy subjects is also planned to understand food effects (FE) on the PK of KT-474. Enrollment of healthy subjects into 2-week multiple ascending dose (MAD) escalation cohorts will be initiated once sufficient safety and PK data from multiple SAD cohorts are available to inform the safe starting dose for the 2-week MAD portion of the study. After the MAD portion in healthy subjects is completed, the safety, PK, and PD of a dose of KT-474 that was found to be safe in healthy subjects when administered for 2 weeks will then be evaluated in AD or HS subjects for 28 days of dosing. Separately, additional multiple dose cohorts evaluating once every other day and/or twice weekly dosing schedules at or below previously evaluated dose levels in healthy volunteers may be initiated.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
154
KT-474 or matching placebo oral tablet(s)
KT-474 oral tablet(s)
Medical Dermatology Specialists
Phoenix, Arizona, United States
Southwest Skin Specialists 32nd St
Phoenix, Arizona, United States
Southwest Skin Specialists Tatum
Phoenix, Arizona, United States
Beatrice Keller Clinic
Sun City West, Arizona, United States
Encore Medical Research, LLC. - Boynton Beach
Boynton Beach, Florida, United States
Research Centers of America
Hollywood, Florida, United States
Encore Medical Research, LLC. - Hollywood
Hollywood, Florida, United States
Encore Medical Research, LLC. - Weston
Weston, Florida, United States
Dermatology and Skin Cancer Center of Leawood
Leawood, Kansas, United States
Dermatology and Skin Cancer Center of Overland Park
Overland Park, Kansas, United States
...and 4 more locations
Incidence and severity of treatment emergent Adverse Events
Time frame: up to 28 days
Incidence and frequency of use of concomitant medication
Time frame: up to 28 days
Area under the curve plasma concentration from time zero to infinity [AUC(0-∞)] (single dose only)
Time frame: up to 28 days
Area under the curve plasma concentration from time zero to last measurable concentration [AUC(0-last)]
Time frame: up to 28 days
Area under the plasma concentration-time curve during a dosing interval [AUC(0-tau)]
Time frame: up to 28 days
Maximum observed plasma concentration (Cmax)
Time frame: up to 28 days
Time to maximum observed plasma concentration (Tmax)
Time frame: up to 28 days
Apparent clearance (CL/F)
Time frame: up to 28 days
Apparent volume of distribution (Vz/F)
Time frame: up to 28 days
Terminal elimination half-life (t1/2)
Time frame: up to 28 days
Mean residence time (MRT)
Time frame: up to 28 days
Renal clearance (CLR)
Time frame: up to 28 days
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