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Recruiting

A Phase 2b Dose-Ranging Study of Oral KT-621 in Adults with Uncontrolled Moderate to Severe Eosinophilic Asthma

Trial ID: 2025-523180-38-00
Protocol: KT621-AS-202
Sponsor: Kymera Therapeutics Inc.

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Diseases & Conditions

Asthma

Objectives

The primary objective of this study is to evaluate the efficacy of multiple doses of KT-621 compared to placebo in adult participants with uncontrolled eosinophilic asthma. Secondary objectives include:

Assessment of the safety and tolerability of multiple doses of KT-621 relative to placebo.
Characterization of the pharmacokinetics of KT-621 in this patient population.

Participants

This study involves 143 participants diagnosed with eosinophilic asthma. The population consists of individuals aged 18 to 75 years, including both males and females. Eligible subjects must have a documented history of asthma for at least 52 weeks and have experienced at least one exacerbation requiring systemic corticosteroids or hospitalization within the preceding year. Clinical requirements include an absolute blood eosinophil count of ≥0.30 x 10^9/L, a fractional exhaled nitric oxide level of ≥ 25 ppb, and a morning pre-bronchodilator FEV1 between 40% and 80% of the predicted normal. Participants must also demonstrate reversible airway obstruction and maintain a stable regimen of inhaled corticosteroids combined with a long-acting beta-agonist. Additionally, an Asthma Control Questionnaire-5 score of ≥ 1.5 is required.

Plans and Procedures

This Phase 2b, randomized, double-blind, placebo-controlled, parallel group, multicenter, dose-ranging study is designed to investigate the efficacy and safety of KT-621 administered orally in adults with uncontrolled moderate to severe eosinophilic asthma. The research methodology involves comparing multiple doses of the investigational product against a matched placebo. The study process begins with a screening visit (V1) to assess eligibility through criteria such as physician-diagnosed asthma, specific blood eosinophil count, FEV1 levels, ACQ-5 scores, and FeNO levels. Following successful screening, participants proceed to a baseline visit (V2) prior to randomization. The primary endpoint is the change from baseline to Week 12 in pre-bronchodilator FEV1. Secondary endpoints include changes in post-bronchodilator FEV1, ACQ-5 score, and AQLQ(S) Global Score, as well as the incidence of treatment-emergent adverse events and plasma PK parameter estimates. The overall trial period is estimated to conclude by December 31, 2027.

Treatment

The experimental medication is KT-621, which is administered in a tablet pharmaceutical form. This substance is intended for oral use.

The control group receives a placebo, consisting of an oral tablet designed to be matched to the appearance of the active medication.

Efficacy

The efficacy of KT-621 in participants with eosinophilic asthma is assessed through several parameters. The primary endpoint is the change from baseline to Week 12 in pre-bronchodilator FEV1. Secondary efficacy assessments include the change from baseline to Week 12 in post-bronchodilator FEV1, the ACQ-5 score, and the AQLQ(S) Global Score. Additionally, plasma PK parameter estimates of KT-621 are evaluated based on plasma concentration time data.

Inclusion and Exclusion Criteria

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Inclusion Criteria

Documented history of at least 1 asthma exacerbation requiring either treatment with systemic corticosteroids (intramuscular, intravenous, or oral) and/or hospitalization or an emergency/urgent medical care visit for acute asthma worsening within the past 52 weeks prior to Screening (V1).
Male or female assigned at birth, inclusive of all gender identities. Contraceptive use by participants or participant partners should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
Must be 18 years old (or the legal age of consent in the jurisdiction in which the study is taking place) to 75 years of age, inclusive, at the time of signing the ICF.
Must have a physician diagnosis of asthma for ≥ 52 weeks prior to the Screening visit (V1), based on the Global Initiative for Asthma (GINA) 2024 guidelines.
Must be on a stable regimen of medium- to high-dose inhaled corticosteroid (ICS) defined as ≥500 µg fluticasone propionate DPI (or equivalent total daily dose) in combination with a long-acting β2-agonist (LABA). The regimen may include additional controller medication (e.g., leukotriene receptor antagonist [LTRA] and/or long-acting muscarinic antagonist [LAMA]). All background controller medications must have been used for ≥12 weeks prior to Screening (V1) and be at a stable dose and regimen with no change in dose or frequency of administration for ≥4 weeks prior to Screening (V1) and between Screening and Baseline (V2).
Morning pre-bronchodilator FEV₁ 40–80% of predicted normal at Screening (V1) and at Baseline (V2), prior to randomization. Up to 2 repeat assessments (3 total) are allowed during the Screening period up to Baseline. If the criterion is not met at Baseline (V2), one additional repeat Baseline visit is permitted within 5 days; at a repeat Baseline visit all baseline assessments must be repeated in full. The qualifying Baseline visit will be used to determine timing of subsequent visits.
ACQ-5 score ≥ 1.5 at the Screening visit (V1) and at the Baseline visit (V2), prior to randomization.
Fractional exhaled nitric oxide (FeNO) ≥25 ppb at Screening (V1) and at Baseline (V2). Up to 2 repeat assessments (3 total) are allowed during Screening up to Baseline. If not met at Baseline (V2), one additional repeat Baseline assessment is permitted within 5 days; at a repeat Baseline visit all baseline assessments must be repeated in full.
Demonstrated evidence of reversible airway obstruction by post-bronchodilator (albuterol/salbutamol) reversibility of FEV₁ at Screening (15–30 minutes after administration of 2–4 puffs of albuterol/salbutamol). Up to 2 repeat assessments (3 total) are allowed during Screening up to Baseline. If applicable, the repeat Baseline allowance described for Criteria 4–6 applies.
Absolute blood eosinophil count must be ≥0.30 x 10^9/L at Screening; up to 2 repeat assessments (3 total) are allowed during the screening period up to the Baseline visit (V2).

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Exclusion Criteria

The presence of any clinically significant pulmonary disease other than asthma, including, but not limited to, active lung infection, chronic obstructive pulmonary disease (COPD), bronchiectasis, pulmonary fibrosis, cystic fibrosis, obesity associated hypoventilation syndrome, lung cancer, alpha 1 antitrypsin deficiency, or primary ciliary dyskinesia. Additionally, any pulmonary or systemic condition other than asthma that is associated with elevated peripheral eosinophil counts, such as allergic bronchopulmonary aspergillosis/mycosis, Churg Strauss syndrome, or hypereosinophilic syndrome.
An asthma exacerbation, requiring either treatment with systemic corticosteroids (intramuscular, intravenous, or oral) and/or hospitalization or an emergency/urgent medical care visit for acute asthma worsening, at any time from 4 weeks prior to the Screening visit (V1) up to and including the Baseline visit (V2).
Has had any of the following at Screening: a. Positive human immunodeficiency virus (HIV) antibody b. Positive hepatitis B (HBV) surface antigen (HBsAg) c. Positive total hepatitis B core antibody (HBcAb) d. Positive hepatitis C virus (HCV) antibody e. Have evidence of active or latent or inadequately treated infection with mycobacterium tuberculosis (TB)
Has any of the following findings at the Screening visit (V1): a. Inadequate hematological function, as follows: i. Platelet count < 100 × 10^9/L (< 100,000/µL) ii. Hemoglobin < 9 g/dL iii. Absolute neutrophil count < 1.5 × 10^9/L (< 1,500/µL) b. Inadequate liver function, as follows: i. Aspartate aminotransferase (AST)/ alanine aminotransferase (ALT) > 2 × upper limit of normal (ULN) ii. Total bilirubin > 1.5 x ULN (participants with Gilbert's syndrome can be included with total bilirubin > 1.5 × ULN) as long as direct bilirubin is ≤ 1.5 x ULN)
Known or suspected history of immunodeficiency disorder, including history of invasive opportunistic infections (eg, histoplasmosis, listeriosis, coccidioidomycosis, pneumocystosis, aspergillosis), despite infection resolution; or unusually frequent, recurrent or prolonged infections, per Investigator's judgment.
Has a clinically significant history or evidence of any active or suspected parasitic infection within 4 weeks of the Baseline visit (V2) or has travelled within the 3 months before Baseline to areas of high parasitic exposure, as determined by local or international health guidelines or epidemiological data.
Has had any major surgery within 8 weeks prior to the Screening visit (V1) or has any planned surgical or medical procedure planned during the study
Has a chronic or acute infection, including upper or lower respiratory tract infection, requiring treatment with systemic antibiotics, antiparasitics, antifungals, or antivirals that were completed within 4 weeks of Baseline or during the Screening period.
Has any other clinically significant disease, condition, or medical history that, in the opinion of the Investigator, would interfere with participant safety, study evaluations, and/or study procedures. Examples include, but are not limited to, participants with short life expectancy, participants with uncontrolled diabetes (hemoglobin A1c ≥9%), partecipants with cardiovascular conditions (eg, heart failure, uncontrolled hypertension), severe renal conditions (eg, participants on dialysis), hepatobiliary conditions (eg, Child Pugh class B or C), neurological conditions (eg, demyelinating diseases), active major autoimmune diseases (such as, but not limited to, lupus, inflammatory bowel disease, rheumatoid arthritis), and other severe endocrinological, gastrointestinal, metabolic, pulmonary, or lymphatic diseases.
Has any medical or psychiatric condition which, in the opinion of the Investigator or the Sponsor's Medical Monitor, would place the participant at risk, interfere with participation in the study, or interfere with the interpretation of study results.
Has a history of alcohol or drug abuse within 2 years of the Screening visit (V1).
Current smokers of nicotine/tobacco as well as non-nicotine products, participants with smoking history of ≥10 pack years, and participants using vaping products, including electronic cigarettes. Former smokers with a smoking history of < 10 pack years and users of vaping or e-cigarette products must have stopped for at least 26 weeks prior to the Screening visit (V1).
Has any cancer or a history of cancers within the last 5 years (except curatively treated with surgical excised squamous cell carcinoma, basal cell carcinoma, or carcinoma in situ of the skin or cervix).

Trial Status by Country

Country	Status	Start of Recruitment	Planned Patients
Austria	Not Yet Recruiting	31 Mar 2026	10
Belgium	Not Yet Recruiting	31 Mar 2026	15
Germany	Recruiting	31 Mar 2026	9
Italy	Not Yet Recruiting	31 Mar 2026	12
Poland	Recruiting	31 Mar 2026	39
Romania	Recruiting	31 Mar 2026	9
Slovakia	Recruiting	31 Mar 2026	9
Spain	Recruiting	31 Mar 2026	18

Sites & Investigators

Research sites

CENTRUM MEDYCZNE LUCYNA ANDRZEJ DYMEK NsP Sv. Jakuba Bardejov n.o.Policlinico “Tor Vergata”, Università degli Studi di Roma TOR VERGATA Bio Zdrowie Sp. z o.o.

Investigators

Agata K.Ismael G. M.Jordi J. P.Jean-Benoit M.

Investigational Products

Details about the medicinal products being studied in this clinical trial.

Product Name	Role in Trial	Formulation	Administration	Max Daily Dose	Treatment Duration	EU MP Number
KT-621	Test	TABLET	ORAL USE	00	12	PRD12800622
Placebo oral tablet matched to KT-621	Placebo	N/A	—	—	—	N/A
KT-621	Test	TABLET	ORAL USE	00	12	PRD12800623
KT-621	Test	TABLET	ORAL USE	00	12	PRD12800621