NCT04772885

A Single and Multiple Ascending Dose Trial of KT-474 in Healthy Adult Volunteers and Patients With Atopic Dermatitis (AD) or Hidradenitis Suppurativa (HS)

A Phase 1 Randomized, Placebo-controlled, Single and Multiple Ascending Dose Trial to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Orally Administered KT-474 in Healthy Adult Volunteers and Patients With Atopic Dermatitis (AD) or Hidradenitis Suppurativa (HS)

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 154 (actual)
• Sponsor: Kymera Therapeutics, Inc. · Industry
• Sex: All
• Age: 18 Years – 55 Years
• Healthy volunteers: Accepted

Summary

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.

Detailed description

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.

Conditions

• Healthy Volunteer
• Atopic Dermatitis
• Hidradenitis Suppurativa

Interventions

Type	Name	Description
DRUG	KT-474/Placebo	KT-474 or matching placebo oral tablet(s)
DRUG	KT-474	KT-474 oral tablet(s)

Timeline

• Start date: 2021-02-23
• Primary completion: 2022-10-20
• Completion: 2022-10-20
• First posted: 2021-02-26
• Last updated: 2022-10-24

Locations

14 sites across 1 country: United States

Regulatory

• FDA-regulated drug study