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

NCT04772885 | Completed Phase 1 FDA Drug

• 1 other identifier: KT474-HV-101
• Study Type: interventional
• Target: 154
• Locations: 1 country
• Sites: 14

Brief 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.

Conditions

Healthy Volunteer; Atopic Dermatitis; Hidradenitis Suppurativa

Keywords

Atopic Dermatitis; Hidradenitis Suppurativa; Immune-inflammatory diseases

Outcome Measures

Primary Outcomes (2)

• Incidence and severity of treatment emergent Adverse Events

  up to 28 days

• Incidence and frequency of use of concomitant medication

  up to 28 days

Secondary Outcomes (10)

• Area under the curve plasma concentration from time zero to infinity [AUC(0-∞)] (single dose only)

  up to 28 days

• Area under the curve plasma concentration from time zero to last measurable concentration [AUC(0-last)]

  up to 28 days

• Area under the plasma concentration-time curve during a dosing interval [AUC(0-tau)]

  up to 28 days

• Maximum observed plasma concentration (Cmax)

  up to 28 days

• Time to maximum observed plasma concentration (Tmax)

  up to 28 days

Other Outcomes (4)

• IRAK4 levels in peripheral blood mononuclear cells

  up to 28 days

• IRAK4 levels in skin

  up to 28 days

• Percentage Change from baseline in Total Abscess and Inflammatory Nodule (AN) Count, Skin Pain Numerical Rating Scale (NRS), Peak pruritis NRS, and HS Physician's Global Assessment (HS-PGA) in HS patients

  up to 42 days

Study Arms (5)

Single ascending dose cohorts in healthy subjects

EXPERIMENTAL

Healthy volunteer subject cohorts randomized 6:2 receiving a single dose of KT-474 or placebo. The first cohort will receive 25 mg of KT-474 or placebo. Dose escalation will occur if KT-474 or placebo is tolerated.

Drug: KT-474/Placebo

Multiple ascending dose cohorts in healthy subjects

EXPERIMENTAL

Healthy volunteer subject cohorts randomized 9:3 to receive KT-474 or placebo for 14 days continuous dosing. The first cohort will receive a dose of KT-474 or placebo determined to be safe based on data generated in the SAD portion.

Drug: KT-474/Placebo

Food Effect Cohort in healthy subjects

EXPERIMENTAL

Healthy Volunteer SAD subject cohorts (up to 5) will receive a single dose of KT-474 in the fed state.

Drug: KT-474/Placebo

Multiple dose cohort in HS and AD patients

EXPERIMENTAL

A single cohort of up to 30 patients with AD or HS to receive a dose of KT-474 determined to be safe based on data generated in the healthy volunteer MAD portion, dosed daily X 28 days.

Drug: KT-474

Multiple dose cohorts in healthy subjects

EXPERIMENTAL

Healthy volunteer subject cohorts randomized 9:3 to receive KT-474 or placebo every other day over 14 days, and/or twice weekly over 15 days. The first cohort will receive a dose of KT-474 or placebo determined to be safe based on data generated in the SAD and MAD portion.

Drug: KT-474/Placebo

Interventions

KT-474/Placebo DRUG

KT-474 or matching placebo oral tablet(s)

Food Effect Cohort in healthy subjects; Multiple ascending dose cohorts in healthy subjects; Multiple dose cohorts in healthy subjects; Single ascending dose cohorts in healthy subjects

KT-474 DRUG

KT-474 oral tablet(s)

Multiple dose cohort in HS and AD patients

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Male and female subjects, including female subjects of child bearing potential, between the ages of 18 and 55 with a weight at least 50 kg and a body mass index (BMI) between 18.0 and 30.0 kg/m2.
• Subjects confirmed as negative in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection test at Screening and on Day -2.
• Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study.
• Agreement and ability to comply with all contraception requirements if applicable.
• All subjects must be willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.

You may not qualify if:

• Evidence or history of a clinically significant medical condition or other condition that might significantly interfere with the absorption, distribution, metabolism, or excretion of study drug, or place the subject at an unacceptable risk as a participant in this study.
• Healthy volunteers who have a clinically relevant history or presence of respiratory, GI, renal, hepatic, hematological, lymphatic, neurological, cardiovascular, psychiatric, musculoskeletal, genitourinary, immunological, dermatological, or connective tissue diseases or disorders.
• Healthy volunteers who have any known factor, condition, or disease that might interfere with treatment compliance, study conduct or interpretation of the results such as drug or alcohol dependence or psychiatric disease.
• Female Healthy volunteers who are pregnant, trying to become pregnant or lactating or breastfeeding.
• Healthy volunteers who have participated in any investigational drug or device clinical study within 3 months prior to first dosing on this study.
• Healthy volunteers who have previously participated in a study with an investigational product or device involving the dosing of a biological targeted at any immune pathway within 1 year prior to Screening.
• Male or female patients aged 18 years to 55 years (inclusive) at the time of Screening, and in generally good health, except for AD or HS, and has a BMI of 17.5 to 35.0 kg/m2; and a total body weight \>50 kg (110 lb).
• Diagnosis of AD or HS for at least 6 months.
• Patients with AD: having at least 10% treatable percentage body surface area at Screening or on Admission (excluding the scalp and designated venous access areas).
• Willingness and ability to comply with all contraception requirements as applicable based on reproductive status.
• Has adequate venous access with venous access sites having AD-unaffected, non-infected skin to permit repeated PK sampling.
• Female patients must have a negative result for the serum pregnancy test at the Screening Visit and on admission.
• Evidence of a personally signed and dated informed consent document indicating that the patient has been informed of all pertinent aspects of the study.
• Patients who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
• Patients with HS: A total Abscess and Inflammatory Nodule count of ≥4 at baseline

Sponsors & Collaborators

• Kymera Therapeutics, Inc.: lead

Study Sites (14)

Medical Dermatology Specialists

Phoenix, Arizona, 85006, United States

Location

Southwest Skin Specialists 32nd St

Phoenix, Arizona, 85018, United States

Location

Southwest Skin Specialists Tatum

Phoenix, Arizona, 85028, United States

Location

Beatrice Keller Clinic

Sun City West, Arizona, 85375, United States

Location

Encore Medical Research, LLC. - Boynton Beach

Boynton Beach, Florida, 33436, United States

Location

Research Centers of America

Hollywood, Florida, 22024, United States

Location

Encore Medical Research, LLC. - Hollywood

Hollywood, Florida, 33021, United States

Location

Encore Medical Research, LLC. - Weston

Weston, Florida, 33331, United States

Location

Dermatology and Skin Cancer Center of Leawood

Leawood, Kansas, 66211, United States

Location

Dermatology and Skin Cancer Center of Overland Park

Overland Park, Kansas, 66223, United States

Location

Dermatology and Skin Cancer Center of Lee's Summit

Lee's Summit, Missouri, 64064, United States

Location

TKL Research

Fair Lawn, New Jersey, 07410, United States

Location

U.S. Dermatology Partners Jollyville

Austin, Texas, 78759, United States

Location

U.S. Dermatology Partners Cedar Park

Cedar Park, Texas, 78613, United States

Location

Related Publications (1)

• Ackerman L, Acloque G, Bacchelli S, Schwartz H, Feinstein BJ, La Stella P, Alavi A, Gollerkeri A, Davis J, Campbell V, McDonald A, Agarwal S, Karnik R, Shi K, Mishkin A, Culbertson J, Klaus C, Enerson B, Massa V, Kuhn E, Sharma K, Keaney E, Barnes R, Chen D, Zheng X, Rong H, Sabesan V, Ho C, Mainolfi N, Slavin A, Gollob JA. IRAK4 degrader in hidradenitis suppurativa and atopic dermatitis: a phase 1 trial. Nat Med. 2023 Dec;29(12):3127-3136. doi: 10.1038/s41591-023-02635-7. Epub 2023 Nov 13.

  PMID: 37957373 DERIVED

MeSH Terms

Conditions

Dermatitis, Atopic; Hidradenitis Suppurativa

Condition Hierarchy (Ancestors)

Skin Diseases, Genetic; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Dermatitis; Skin Diseases; Skin and Connective Tissue Diseases; Skin Diseases, Eczematous; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Skin Diseases, Bacterial; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Skin Diseases, Infectious; Suppuration; Hidradenitis; Sweat Gland Diseases

Study Officials

• Ashwin Gollerkeri, MD

  Kymera Therapeutics, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: randomized double blind (for Parts A and B only)
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Single ascending dose escalation and multiple ascending dose escalation study followed by an evaluation of food effects on absorption

Study Record Dates

• First Submitted: February 12, 2021
• First Posted: February 26, 2021
• Study Start: February 23, 2021
• Primary Completion: October 20, 2022
• Study Completion: October 20, 2022
• Last Updated: October 24, 2022

Record last verified: 2022-10

Locations

US (14)