Clinical trial NCT06673667: First-in-human Study of Orally Administered KT-621 in Healthy Adult Participants
Official title: A Phase 1, Randomized, Placebo-Controlled, First-in-Human, Single and Multiple Ascending Dose Study Designed to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Orally Administered KT-621 in Healthy Adult Participants
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Healthy Participants Study
Keywords: Phase 1
STAT6
STAT6 degrader
targeted protein degrader
Lead sponsor: Kymera Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2024-11-05
Enrollment: 120
Sex: ALL
Minimum age (years): 19
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: OTHER

Brief summary: This is a first-in-human study to evaluate safety, pharmacokinetics, and pharmacodynamics of single and multiple dose levels of KT-621 in healthy male and female adult participants.


Eligibility criteria: Inclusion Criteria:

* Participants aged 19 to 55 years (inclusive) at the time of consent, with a weight of at least 50 kg if male or 40 kg if female, and a body mass index (BMI) between 18.0 and 30.0 kg/m² (inclusive) at Screening.
* Evidence of a personally signed and dated informed consent document indicating that the participant has been informed of all pertinent aspects of the study.
* Participants must be willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
* Male participants (and their partners of childbearing potential) and female participants must agree to the contraception requirements as specified in the clinical protocol.
* Female participants may not be pregnant, lactating, or breast-feeding or plan to become pregnant (including ova donation) within 30 days of last study drug administration.
* Female participants must have a negative result for pregnancy test at Screening and on admission to the CRU.

Exclusion Criteria:

* Participants who have a clinically relevant history of respiratory, gastrointestinal (GI), renal, hepatic, hematological, lymphatic, endocrinological, neurological, cardiovascular, psychiatric, musculoskeletal, genitourinary, immunological, dermatological, ophthalmological, or connective tissue diseases or disorders.
* Participants who have a clinically relevant surgical history (eg, surgery of the GI tract that could interfere with the PK of the trial medication) Note: prior appendectomy or cholecystectomy is not exclusionary.
* Participants with a history of alcohol or substance abuse within the previous 5 years.
* Participants 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.
* Participants who test positive for alcohol and drugs of abuse at Screening and on admission to the CRU.
* Participants who have acute GI symptoms at the time of Screening or admission to the CRU (eg, nausea, vomiting, diarrhea, heartburn).
* Participants whose results from clinical laboratory safety tests are outside the local reference range at Screening and on admission to the CRU.
* Participants who have previously received KT-621 in another cohort in this study.
* Participants who have been dosed with any investigational drug or device in a clinical study within 30 days or 5 half-lives (whichever is longer) of KT-621/placebo administration.

Primary outcomes:
measure: Incidence of adverse events
timeFrame: From enrollment through the safety follow-up visit on either Day 14 (SAD) or Day 38 (MAD)
measure: Treatment-emergent potentially clinically-significant abnormalities in safety laboratory parameters: hematology
timeFrame: From enrollment through the safety follow-up visit on either Day 14 (SAD) or Day 38 (MAD)
measure: Treatment-emergent potentially clinically significant abnormalities in safety laboratory parameters: serum chemistry
timeFrame: From enrollment through the safety follow-up visit on either Day 14 (SAD) or Day 38 (MAD)
measure: Treatment-emergent potentially clinically significant abnormalities in safety laboratory parameters: coagulation
timeFrame: From enrollment through the safety follow-up visit on either Day 14 (SAD) or Day 38 (MAD)
measure: Treatment-emergent potentially clinically significant abnormalities in electrocardiogram values: QTcF (milliseconds)
timeFrame: From enrollment through the safety follow-up visit on either Day 14 (SAD) or Day 38 (MAD)
measure: Treatment-emergent potentially clinically significant abnormalities in vital signs: heart rate (beats per minute)
timeFrame: From enrollment through the safety follow-up visit on either Day 14 (SAD) or Day 38 (MAD)
measure: Treatment-emergent potentially clinically significant abnormalities in vital signs: blood pressure (mmHg)
timeFrame: From enrollment through the safety follow-up visit on either Day 14 (SAD) or Day 38 (MAD)
measure: Treatment-emergent potentially clinically significant abnormalities in vital signs: respiratory rate (breaths per minute)
timeFrame: From enrollment through the safety follow-up visit on either Day 14 (SAD) or Day 38 (MAD)
measure: Treatment-emergent potentially clinically significant abnormalities in vital signs: temperature (degrees Celsius)
timeFrame: From enrollment through the safety follow-up visit on either Day 14 (SAD) or Day 38 (MAD)
Secondary outcomes:
measure: Maximum concentration (Cmax): observed maximum concentrations derived from plasma concentration data
timeFrame: Day 1 (SAD); Day 1, Day 7, and Day 14 (MAD)
measure: Time to maximum concentration (Tmax): observed time to achieve maximum concentrations derived from plasma concentration data
timeFrame: Day 1 (SAD); Day 1, Day 7, and Day 14 (MAD)
measure: Area under the curve (AUC0-last): Area under the plasma concentration-time curve calculated using non-compartmental analysis from time zero to the last observed timepoint
timeFrame: Day 1 (SAD); Day 1, Day 7, and Day 14 (MAD)
measure: Area under the curve (AUC0-infinity): Area under the plasma concentration-time curve calculated using non-compartmental analysis from time zero to infinite time
timeFrame: Day 1 (SAD)
measure: Area under the curve (AUC0-tau): Area under the plasma concentration-time curve calculated using non-compartmental analysis from time zero to end of the dosing interval
timeFrame: Day 1, Day 7, and Day 14 (MAD)
measure: Terminal elimination half-life (t1/2): elimination half-life calculated using non-compartmental analysis
timeFrame: Day 1 (SAD) and Day 14 (MAD)
measure: Fraction excreted: Fraction of drug excreted unchanged in urine
timeFrame: Day 14 (MAD)
Other outcomes:
measure: Change from baseline in STAT6 protein levels in whole blood and peripheral blood mononuclear cells (SAD)
timeFrame: Day 1
measure: Change from baseline in STAT6 protein levels in whole blood, peripheral blood mononuclear cells, and skin (MAD)
timeFrame: Day 1 to Day 14
Locations:
city: Lincoln
country: United States
facility: Celerion
state: Nebraska
Study officials:
References: