A Clinical Trial in Healthy Volunteers and Patients With Mild Asthma to Investigate a New Medicine (AZD4604) for the Treatment of Asthma

Launched by ASTRAZENECA · Feb 24, 2021

Keywords

ClinConnect Summary

Part 1a of the study will be a randomized, single-blind, placebo-controlled, SAD, sequential group design study. Seven inhaled dose levels of AZD4604 are planned to be investigated in cohorts of 8 healthy volunteers, with 6 healthy volunteers randomly assigned to inhaled AZD4604 and 2 healthy volunteers randomly assigned to inhaled placebo in each cohort.

Part 1a will comprise of:

* A Screening Visit within 28 days before dosing.
* A Treatment Period (Day -1 to Day 7, in the Clinical Unit) with a single inhaled dose of AZD4604 or corresponding placebo on Day 1. Although the anticipated sy...

Gender

ALL

Eligibility criteria

• Inclusion criteria:
• All Study Parts:
• • Provision of signed and dated, written informed consent prior to any study specific procedures.
• * Female subjects must have a negative pregnancy test at the Screening Visit and on admission to the Study Center or prior to randomization for Part 3 (Day -1 or Day 1 visit) and must not be lactating. Women of non-childbearing potential, must fulfill one of the following criteria:
• • Postmenopausal defined as amenorrhea for at least 12 months or more following cessation of all exogenous hormonal treatments and follicle stimulating hormone levels in the postmenopausal range.
• • Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not bilateral tubal ligation.
• • Male subjects and their Women of childbearing potential (WOCBP) partners should be willing to use highly effective contraception measures and should refrain from donating sperm or fathering a child from the first day of dosing until 3 months after the last dose of investigational medicinal product (IMP).
• • WOCBP must be willing to use highly effective contraception measures from the first day of dosing until at least 1 month after the last dose of IMP, such as measures that results in low failure rate, ie, less than 1% per year.
• Part 1a, Part 1b, and Part 2 Only:
• • Healthy male and female (including WOCBP) volunteers aged 18 to 55 years with suitable veins for cannulation or repeated venipuncture.
• • Have a BMI between 18 and 30 kg/m2 inclusive and weigh at least 60 kg.
• Part 1a and Part 2 Only:
• • - Healthy volunteers must have a FEV1 ≥ 80% of the predicted value regarding age, height, gender and ethnicity at the Screening and the Randomization Visits in accordance with American Thoracic Society (ATS)/ European Respiratory Society (ERS) criteria.
• Part 3 Only:
• • Male and female (including WOCBP) patients with mild asthma aged 18 to 65 years with suitable veins for cannulation or repeated venipuncture.
• • Have a BMI between 18 and 35 kg/m2 inclusive and weigh at least 60 kg.
• • Physician diagnosed mild asthma for at least 6 months prior to Screening Visit.
• • Lung function ≥ 70% predicted for FEV1 at the Screening Visit AND on pre-morning dose Day -1, in accordance with the ATS/ERS criteria.
• • Have a FeNO of ≥ 40 ppb at the Screening Visit and at the corresponding clock-time of pre-morning dose on Day-3.
• • Must have evidence of up-to-date Coronavirus disease 2019 (COVID-19) vaccination status as per local guidelines.
• Exclusion criteria:
• All Study Parts:
• • History of any clinically important disease or disorder.
• • Subject has an increased risk of infection.
• • History of cancer within the last 10 years except for basal and squamous cell carcinoma of the skin or in situ carcinoma of the cervix treated and considered cured.
• • Disease history suggesting abnormal immune function.
• • Have received any vaccine in the 30 days prior to the first dose.
• • Has a body temperature of \> 37.7°C on Day-1.
• • History or presence of gastrointestinal, hepatic or renal disease.
• • Any clinically important illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of Investigational medicinal product (IMP).
• • High-sensitivity C-reactive protein \> upper limit of normal (ULN) at Screening Visit and on Day -1.
• • Any clinically important abnormalities in clinical chemistry, hematology or urinalysis results. Consider appropriate ethnicity adjusted local reference ranges for hematology measurements, when available.
• • Abnormal vital signs at the Screening Visit, after 5 minutes supine rest.
• • Known or suspected history of drug abuse.
• • Current smokers or those who have smoked or used nicotine products.
• • History of alcohol abuse or excessive intake of alcohol.
• • Positive screen for drugs of abuse or cotinine (nicotine).
• • History of severe allergy/hypersensitivity or ongoing clinically important allergy/hypersensitivity, or history of hypersensitivity to drugs with a similar chemical structure or class to AZD4604.
• • Excessive intake of caffeine containing drinks or food (eg, coffee, tea, chocolate).
• • Use of drugs with enzyme inducing properties such as St John's Wort within 3 weeks prior to the first administration of investigational medicinal product.
• • Plasma donation within one month of the Screening Visit or any blood donation/blood loss \> 500 mL during the 3 months prior to the Screening Visit.
• • Has received another new chemical entity (defined as a compound which has not been approved for marketing) within 3 months of the first administration of IMP in this study.
• • Involvement of any AstraZeneca or study Center employee or their close relatives.
• • Subject should not participate in the study if they have any ongoing or recent minor medical complaints that may interfere with the interpretation of study data.
• • Subjects who cannot communicate reliably.
• • Vulnerable subjects.
• • Any clinically important abnormalities in rhythm, conduction or morphology of the resting electrocardiogram (ECG) and any clinically important abnormalities in the 12 lead ECG that may interfere with the interpretation of QTc interval changes, including abnormal ST T wave morphology, particularly in the clinical study protocol (CSP) defined primary lead or left ventricular hypertrophy.
• • Female subjects who are planning a pregnancy during the study period or within 1 month after the last dose of IMP.
• Part 1a, Part 1b, and Part 2 Only:
• • Any laboratory values with the deviations at the Screening Visit and on Day 1.
• • Persistent or intermittent complete Bundle branch block (BBB), Incomplete bundle branch block (IBBB), or Intraventricular conduction delay (IVCD) with ECG interval measured from the onset of the QRS complex to the J point (QRS) \> 110 ms.
• • Subjects who have medical dietary restrictions or dietary restrictions which the site are unable to cater for.
• • Use of any prescribed or nonprescribed medication during the 2 weeks prior to the first administration of IMP or longer if the medication has a long half life.
• • History of any respiratory disorders.
• • Clinically significant history of allergic rhinitis/hay fever or anaphylaxis.
• Part 3 Only:
• • Exacerbation of asthma symptoms and requiring the use of oral or IV steroids, antibiotics, Accident and Emergency visit, or hospital admission.
• • Any laboratory values with the deviations at the Screening Visit and on Day -1. Abnormal values may be repeated once at the discretion of the PI: (a)Alanine aminotransferase \> 1.25 × upper-limit of normal (ULN); (b)Aspartate aminotransferase \> 1.25 × ULN; (c)Total bilirubin \> 1.25 × ULN; (d) Creatinine \> ULN; (e)Absolute neutrophil count \< lower limit of normal (LLN) at the Screening Visit; (f) Absolute lymphocyte count \< LLN at the Screening Visit; (g)Hemoglobin \< LLN
• • Persistent or intermittent complete BBB, IBBB, or IVCD with QRS \> 110 ms. Patients with IVCD and QRS \<120 ms are acceptable if there is no evidence of eg, ventricular hypertrophy or pre-excitation.
• • Use of the following medicines before Screening Visit: Long-acting β2 agonists; Biologics for asthma; Inhaled corticosteroids (ICS) \> 500 μg per day of beclometasone dipropionate or equivalent; Any ICS at any dose; Oral or injectable steroids for treatment of asthma or respiratory tract infection; Intranasal steroids; Leukotriene antagonists; Xanthines (excluding caffeine), anticholinergics, or cromoglycate; Short-acting bronchodilator other than for rescue.