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

• Status: Recruiting
• Trial end date: 2022-02-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Kymera Therapeutics, Inc.

Criteria

Healthy Volunteer (Parts A and B) Inclusion Criteria:

1. 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.

2. Subjects confirmed as negative in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection test at Screening and on Day -2.

3. Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study.

4. Agreement and ability to comply with all contraception requirements if applicable.

5. All subjects must be willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.

Healthy Volunteer (Parts A and B) Exclusion Criteria:

1. 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.

2. 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.

3. 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.

4. Female Healthy volunteers who are pregnant, trying to become pregnant or lactating or breastfeeding.

5. Healthy volunteers who have participated in any investigational drug or device clinical study within 3 months prior to first dosing on this study.

6. 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.

AD or HS Patient (Part C) Inclusion Criteria:

1. 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).

2. Diagnosis of AD or HS for at least 6 months.

3. Patients with AD: having at least 25% treatable percentage body surface area at Screening or on Admission (excluding the scalp and designated venous access areas).

4. Willingness and ability to comply with all contraception requirements as applicable based on reproductive status.

5. Has an Investigator's static global assessment score of moderate (3) or severe (4) at Screening or on Day -1.

6. Has adequate venous access with venous access sites having AD-unaffected, non-infected skin to permit repeated PK sampling.

7. Female patients must have a negative result for the serum pregnancy test at the Screening Visit and at the follow-up visit.

8. Evidence of a personally signed and dated informed consent document indicating that the patient has been informed of all pertinent aspects of the study.

9. Patients who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.

AD or HS Patient (Parts C) Exclusion Criteria:

1. Has any clinically significant medical disorder, condition, disease (including active or potentially recurrent dermatological conditions other than AD or HS), significant physical examination or laboratory findings that may interfere with study objectives, in the Investigator's opinion (eg, conditions or findings that may expose a patient to unacceptable risk by study participation, confound the evaluation of treatment response or adverse events, or otherwise interfere with a patient's ability to complete the study).

2. Has unstable AD or HS or a consistent requirement for strong to strongest potency topical corticosteroids to manage AD or HS signs and symptoms.

3. Has an active systemic or localized infection, including known actively-infected AD or HS.

4. Treatment with an investigational product within 30 days or 5 half-lives preceding the first dose of investigational product (whichever is longer).

5. Use of prescription or nonprescription drugs including topical corticosteroids, vitaminic and dietary supplements within 14 days or 5 half-lives (whichever is longer) prior to the first dose of investigational product.

6. Blood donation (excluding plasma donations and platelet donations) of approximately ≥400 mL within 3 months or ≥200 mL within a month prior to dosing.

7. History of sensitivity to heparin or heparin-induced thrombocytopenia.

8. Unwilling or unable to comply with the protocol procedures and/or assessments.

9. Other acute or chronic medical or psychiatric condition including recent (within the past year) or active suicidal ideation or behavior or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the patient inappropriate for entry into this study.