临床试验/NCT05110976

NCT05110976已完成1 期

Phase I, Randomised, Blinded, Placebo-controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AZD8630 in Healthy Adult Subjects (Part A) and Adults With Asthma on Medium to High Dose Inhaled Corticosteroids and Long-acting Beta-agonists (Part B)

AstraZeneca1 个研究点分布在 1 个国家目标入组 170 人开始时间: 2021年12月16日最近更新: 2023年8月30日

适应症

干预措施

试验速览

阶段: 1 期
状态: 已完成
发起方: AstraZeneca
入组人数: 170
试验地点: 1
主要终点: Part A (IV cohort): Maximum observed serum (peak) drug concentration (Cmax) of AZD8630

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

This is a first in human (FIH) clinical study to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of AZD8630 in healthy adults (Part A) and adult asthma patients on medium to high dose inhaled corticosteroids / Long-acting beta-agonists (Part B)

详细描述

The study is divided in 2 parts, A and B.

Part A will be conducted in healthy adults, whereas Part B will be conducted in adult asthma patients on medium/high dose inhaled corticosteroids (ICS)/long-acting beta-agonists (LABA) to evaluate the safety, tolerability, pharmacokinetics (PK), and immunogenicity of AZD8630 by dry powder inhaler (DPI) administration. Part A includes the assessment of the PK and safety of intravenous (IV) AZD8630. Part A consists of single ascending dose (SAD) and multiple ascending dose (MAD) cohorts in sequential order and Part B will be evaluating multiple dose levels.

Part A: This part will consist 4 sub-parts and will include healthy participants and healthy participants of Chinese and Japanese ethnicity. These participants will randomized to receive AZD8630 and to receive placebo.

Sub-Part A1, SAD in healthy participants (one cohort in Sub-Part A1 will receive IV AZD8630 [IV formulation])
Sub-Part A2, SAD in healthy participants of Chinese and Japanese ethnicity
Sub-Part A3, MAD in healthy participants
Sub-Part A4, MAD in healthy participants of Chinese and Japanese ethnicity

Part B: Adult asthma patients will be randomized to one of 3 inhaled dose levels of AZD8630 or placebo.

研究设计

研究类型: Interventional
分配方式: Randomized
干预模型: Sequential
主要目的: Other
盲法: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

盲法说明

Part A of the study is single-blind, and Part B of the study is double-blind

入排标准

年龄范围: 18 Years 至 75 Years（Adult, Older Adult）
性别: All
接受健康志愿者: 是

入选标准

•Part A (Healthy participants):
•Healthy participants aged 18 to 55 years, inclusive:
•Japanese participants must be aged 20 to 55 years, inclusive
•Chinese participants must be aged 18 to 45 years, inclusive
•Females must have a negative serum pregnancy test at the Screening Visit and a negative urine pregnancy test on admission to the Clinical Unit, must not be lactating, and must be of non childbearing potential, confirmed at the Screening Visit
•Have a body mass index (BMI) between 18 and 30 kg/m^2 inclusive and weigh at least 45 kg.
•Healthy participant must have a forced expiratory volume in 1 second (FEV1) ≥ 80% of the predicted value regarding age, height, gender, and ethnicity at the Screening Visit.
•Male participants and their women of childbearing potential partners (WOCPB) should be willing to use highly effective contraception measures and male participants should refrain from donating sperm or fathering a child from the first day of dosing until 3 months after the study Follow up Visit.
•Part A2 and Part A4 (Chinese population only): Chinese participants must have been born in China, have all parents and grandparents of Chinese origin, and not have lived outside of China for more than 10 years.
•Part A2 and Part A4 (Japanese population only): Japanese participants must have been born in Japan, have all parents and grandparents of Japanese origin, and not have lived outside of Japan for more than 10 years.
•Part B (Participants with Asthma):
•Male and female including WOCBP participants with asthma aged 18 to 75 years inclusive, with suitable veins for cannulation or repeated venipuncture.
•Have a BMI between 18 and 35 kg/m^2 inclusive and weigh at least 45 kg.
•Confirmed physician-led diagnosis of asthma for > 6 months before the Screening Visit.
•Any of the following assessments within the last 10 years to confirm variable airflow obstruction: Variability between clinic visits: FEV1 > 12% and 200 mL; Response to 4 weeks' anti-inflammatory therapy: FEV1 > 12% and 200 mL; Exercise challenge test: FEV1 fall > 10% and 200mL; Methacholine challenge test: FEV1 ≥ 20% fall at < 8 mg/mL; Indirect challenge test: FEV1 ≥ 15% fall; Or in the screening period: Variability between clinic visits: FEV1 > 12% and 200 mL; Peak expiratory flow rate (PEFR) for 2 weeks during run-in: PEFR average daily variability > 10%.
•Pre-bronchodilator FEV1 ≥ 40% and < 85% predicted at the Screening Visit.
•Have a fractional exhaled nitric oxide (FeNO) of ≥ 35 ppb at the Screening Visit and ≥ 30 ppb at randomisation.
•Asthma Control Questionnaire -5 score of ≥ 0.75 and ≤ 3.0 at screening.
•During 7 consecutive days within screening, immediately prior to randomisation demonstrates ≥ 65% adherence to each of the following:
•Once daily home FeNO
•Twice daily home spirometry measurements
•Twice daily entries in the eDiary
•Females must have a negative serum pregnancy test at the Screening Visit. Additionally, WOCBP must have a negative urine pregnancy test at Visit 2 (prior to randomisation) and must not be lactating.
•Male participants and their WOCBP partners should be willing to use highly effective contraception measures and male participants should refrain from donating sperm or fathering a child from the first day of dosing until 3 months after the study Follow-up Visit.
•WOCBP must be willing to use highly effective contraception measures from the first day of dosing until 3 months after the study Follow up Visit.

排除标准

•Part A (Healthy participants)
•History of following: any clinically important disease or disorder; any upper or lower respiratory tract infection during screening period; active tuberculosis or current positive result for Interferon gamma release assay at screening; clinically significant history of atopy or allergy to common allergens including house dust mite and pollens, or a history of childhood asthma.
•Active or previous hepatitis B, hepatitis C, or Human immunodeficiency virus at the Screening Visit, and other latent or chronic infections.
•History of severe COVID-19 (Coronavirus disease 2019) infection requiring hospitalization
•SARS-CoV-2 (Severe acute respiratory syndrome coronavirus 2) first vaccination within 30 days prior to screening.
•SARS-CoV-2 second or booster vaccination within 10 days of screening.
•Unwilling to defer SARS-CoV-2 vaccination during the study period.
•History of cancer within last 10 years (20 years for breast cancer) except for basal and squamous cell carcinoma of skin or in situ carcinoma of cervix treated and considered cured. Any history of lymphoma is not allowed.
•Have received live or live attenuated vaccine in 4 weeks prior to randomisation.
•History of acquired or inherited immunodeficiency disorders including but not limited to HIV, COVID-19, or taking immune replacement therapy.
•C-reactive protein above upper limit of laboratory reference range
•Any clinically important abnormalities in clinical chemistry, haematology or urinalysis results and abnormal vital signs at the Screening Visit.
•Current smokers or those who have smoked or used nicotine or inhalational cannabis/marijuana products. History of alcohol abuse or drug abuse.
•Use of any prescribed or nonprescribed medication during the 2 weeks prior to the first administration of investigational medicinal product.
•Has received another new chemical entity.
•History of severe allergy/hypersensitivity or ongoing clinically important allergy/hypersensitivity, as judged by the investigator, or history of hypersensitivity to drugs with a similar chemical structure or class to AZD
•History of anaphylaxis to any previous biological therapy.
•Participants who have previously received AZD
•Part B (Participants with Asthma):
•History of following: any clinically important disease or disorder; any chronic respiratory disorders (except asthma) such as Chronic obstructive pulmonary disease, bronchiectasis, or IPF; clinically significant lower respiratory tract infection not resolved within 4 weeks prior to screening.
•Acute exacerbation of asthma requiring hospitalisation and/or attendance at an emergency department and/or systemic corticosteroids within 6 weeks of randomisation.
•History of active TB or a current positive result for IGRA at screening.
•History of severe COVID-19 infection requiring hospitalisation.
•SARS-CoV-2 first vaccination within 30 days prior to screening.
•SARS-CoV-2 second or booster vaccination within 10 days of screening.
•Confirmed COVID-19 infection during screening, prior to randomisation.
•History of cancer within the last 10 years (20 years for breast cancer) except for basal and squamous cell carcinoma of the skin or in situ carcinoma of the cervix treated and considered cured. Any history of lymphoma is not allowed.
•Have received live or live attenuated vaccine in the 4 weeks prior to randomisation.
•C-reactive protein above the upper limit of laboratory reference range at screening.
•Any clinically important abnormalities in clinical chemistry, haematology or urinalysis results, and abnormal vital signs at the Screening Visit.
•Current smokers or those who have smoked or used nicotine or inhalational cannabis/marijuana products. History of alcohol or drug abuse.
•Positive screen for drugs of abuse or cotinine (nicotine) prior to randomisation.
•Use of drugs with enzyme inducing properties such as St John's Wort within 3 weeks before first administration of study drug.
•Use of any prescribed or nonprescribed medication during the 2 weeks prior to the first administration of study drug.
•Use of following medicines within specified time before Screening: (a) Any biologics for asthma within 6 months prior to Screening; (b) Systemic or intranasal steroids within 4 weeks prior to Screening; (c) Xanthines, anticholinergics, or cromoglycate within 1 week prior to Screening; (d) Short acting bronchodilator other than for rescue and within 12 hours prior to Screening and Day -1 assessments.
•History of anaphylaxis or ongoing clinically important serious allergy, or history of hypersensitivity or anaphylaxis to drugs with a similar chemical structure or class to AZD
•History of anaphylaxis to any previous biological therapy.
•Pregnancy or intention to become pregnant during course of study, breastfeeding, or unwillingness to use a highly effective method of contraception throughout study in female participants of childbearing potential or lactating woman.

研究组 & 干预措施

Part A1: SAD (AZD8630)

Experimental

Healthy participants will receive single inhaled doses 1 to 5 of AZD8630.

干预措施: AZD8630 (Drug)

Part A1: IV (AZD8630)

Experimental

Healthy participants will receive a single IV dose of AZD8630.

干预措施: AZD8630 (Drug)

Part A1: IV (Placebo)

Placebo Comparator

Healthy participants will receive single IV dose of Placebo.

干预措施: Placebo (Drug)

Part A2: SAD (AZD8630)

Experimental

Healthy participants of Chinese and Japanese ethnicity will receive single inhaled dose 5 of AZD8630.

干预措施: AZD8630 (Drug)

Part A3: MAD (AZD8630)

Experimental

Healthy participants will receive once daily inhaled doses 3, 4, and 5 of AZD8630.

干预措施: AZD8630 (Drug)

Part A4: MAD (AZD8630)

Experimental

Healthy participants of Chinese and Japanese ethnicity will receive once daily inhaled dose 5 of AZD8630.

干预措施: AZD8630 (Drug)

Part A: SAD (Placebo)

Placebo Comparator

Healthy participants and healthy participants of Chinese and Japanese ethnicity will receive single inhaled doses of placebo.

干预措施: Placebo (Drug)

Part A: MAD (Placebo)

Placebo Comparator

Healthy participants and healthy participants of Chinese and Japanese ethnicity will receive once daily inhaled dose of placebo.

干预措施: Placebo (Drug)

Part B (AZD8630)

Experimental

Participants with asthma will be randomized to one of 3 inhaled dose levels 3, 6, and 7 of AZD8630 once daily.

干预措施: AZD8630 (Drug)

Part B (Placebo)

Placebo Comparator

Participants with asthma will receive once daily inhaled dose of placebo.

干预措施: Placebo (Drug)