A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of SHR-4597 Inhalation in Healthy Subjects and Asthmatic Patients

NCT06385964 | Completed Phase 1

• 1 other identifier: SHR-4597-101
• Study Type: interventional
• Target: 62
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective of this randomized, double-blind, single/multiple ascending dose, placebo-controlled Phase I clinical trial was to evaluate the safety and tolerability of SHR-4597 in healthy subjects and asthmatic patients. The study consists of two parts: Part 1 involves single ascending inhalation dose in healthy subjects; Part 2 involves multiple ascending inhalation dose in asthmatic patients, further divided into Part 2A: multiple ascending inhalation dose in mild to moderate asthmatic patients, and Part 2B: multiple ascending inhalation dose in moderate to severe asthmatic patients. Subsequent lung pharmacokinetic studies of SHR-4597 inhalation will be conducted based on patients' PKPD data.

Conditions

Healthy Subjects; Asthmatic Patients

Outcome Measures

Primary Outcomes (2)

• Incidence and severity of inhalant adverse events after 4 days of single inhalation of SHR4597 in healthy subjects

  4 days for healthy subjects

• Incidence and severity of inhalant adverse events after 16 days of multiple inhalation of SHR4597 in asthmatic patients,

  16 days for asthmatic patients.

Study Arms (2)

SHR-4597

EXPERIMENTAL

Drug: SHR-4597

SHR-4597 Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

SHR-4597 DRUG

SHR-4597 by dry powder inhalation

SHR-4597

Placebo DRUG

Placebo by dry powder inhalation

SHR-4597 Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy subjects:
• Understand the specific procedures of the trial, voluntarily participate in this trial, and sign the informed consent form in writing.
• Aged between 18 and 55 years old (inclusive of boundary values).
• Male subjects with a weight of ≥ 50 kg and female subjects with a weight of ≥ 45 kg, with a body mass index (BMI) between 18 and 30 kg/m2 (inclusive of boundary values).
• Vital signs, physical examinations, laboratory tests, chest X-rays, etc., are either normal or clinically insignificant in abnormalities.
• Female subjects of reproductive potential or male subjects whose partners are of reproductive potential must agree, from the time of signing the informed consent form until 1 month after the last dose of study drug administration, to have no plans for pregnancy and voluntarily adopt effective contraception measures (including partners), while also avoiding sperm/egg donation (see Appendix 1 for details).
• During the study period, participants must be able to comply with all study regulations and procedures and be able to use the inhalation device used in this study correctly.
• Asthma patients:
• Age ≥ 18 years and ≤ 75 years, gender not specified.
• Body Mass Index (BMI) during screening period ≥ 18 and ≤ 30 kg/m2.
• History records and objective evidence of asthma diagnosis meeting current guidelines in the 12 months prior to randomization.
• Not received any asthma treatment or only used short-acting bronchodilators (SABA) on an as-needed basis in the 4 weeks prior to randomization; or received maintenance therapy with medium to high daily doses of inhaled corticosteroids (ICS) and/or other asthma control medications for at least 3 months prior to randomization, and the dosage regimen and asthma condition remained stable in the 4 weeks prior to randomization.
• FEV1 ≥ 60% or ≥40% and \< 80% of predicted value before inhalation bronchodilator use during screening and baseline.
• FeNO value ≥ 25 ppb during screening and baseline.
• Female subjects of reproductive potential or male subjects whose partners are of reproductive potential must agree, from the time of signing the informed consent form until 1 month after the last dose of study drug administration, to have no plans for pregnancy and voluntarily adopt effective contraception measures (including partners), while also avoiding sperm/egg donation (see Appendix 1 for details).

You may not qualify if:

• Healthy subjects:
• Suffering from any clinically serious disease such as circulatory, endocrine, nervous, digestive, respiratory, hematological, immunological, psychiatric and metabolic abnormalities, or any other disease that might interfere with the study results;
• Previous history of malignant tumor;
• Current or recent (within 3 months) respiratory disease or a history of severe respiratory disease, and researchers assess that it may affect drug absorption or pose a safety risk;
• Patients with severe infection, severe trauma or major surgical operation within 3 months before administration; Patients who plan to undergo surgery during the trial period and within two weeks of its end;
• lead ECG abnormalities are clinically significant or ECG QT interval (QTc) \> 450 ms in male subjects and ECG QTc \> 470 ms in female subjects;
• Screening for infectious diseases during the screening period, including positive results for hepatitis B surface antigen (HBsAg), hepatitis C virus antibody, human immunodeficiency virus antibody, and syphilis treponema antibody;
• People with a suspected history of allergy to the investigational drug or any of the ingredients in the investigational drug, allergies or a history of severe drug allergy;
• Previous blood collection difficulties or can not tolerate venipuncture, such as fainting needle, fainting blood
• Had taken any prescription, over-the-counter, or Chinese herbal medicine within 14 days prior to taking the study drug, or within 5 half-lives of the drug at the time of screening; Plan to take non-study medications during the trial period.;
• Participants who have participated in clinical trials of any drug or medical device within 3 months prior to screening, or those still within 5 half-lives of a drug prior to screening (whichever is longer);
• Blood donation or blood loss ≥ 200 mL within 1 month prior to administration, or blood donation or blood loss ≥ 400 mL within 3 months prior to administration, or received blood transfusion within 8 weeks;
• Average smoking ≥ 5 cigarettes per day in the three months prior to administration; More than 15 g of alcohol per day on average in the month prior to administration (15 g of alcohol is equivalent to 450 mL of beer or 150 mL of wine or 50 mL of low-alcohol liquor);
• People who do not refrain from smoking, drinking or consuming caffeinated food or beverages (more than 8 cups, 1 cup = 250 mL) 2 days before administration and during the trial period; Those who cannot prohibit the consumption of grapefruit or grapefruit juice; And those who have special requirements for diet and cannot comply with a unified diet;
• Subjects who are pregnant (tested positive during screening or baseline pregnancy test) or who plan to become pregnant while breastfeeding or during the study;

Sponsors & Collaborators

• Guangdong Hengrui Pharmaceutical Co., Ltd: lead

Study Sites (1)

West China Hospital of Sichuan University

Chengdu, Sichuan, 200433, China

Location

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 23, 2024
• First Posted: April 26, 2024
• Study Start: May 7, 2024
• Primary Completion: February 19, 2025
• Study Completion: February 19, 2025
• Last Updated: March 6, 2026

Record last verified: 2026-03

Locations

CN (1)