A Study to Investigate the Safety, Tolerability and Effects of AZD8630 in Healthy Subjects and Subjects With Asthma on Inhaled Corticosteroids and Long-acting Beta-agonists

NCT05110976 | Completed Phase 1 FDA Drug

• 2 other identifiers: D6830C000012021-004000-18
• Study Type: interventional
• Target: 170
• Locations: 3 countries
• Sites: 29

Brief Summary

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)

Conditions

Asthma

Keywords

Healthy adult participants; Healthy participants of Chinese and Japanese ethnicity; Corticosteroids Beta-agonists; Multiple ascending dose; Single ascending dose

Outcome Measures

Primary Outcomes (14)

• Part A and Part B: Number of participants with adverse events

  Safety and tolerability of inhaled AZD8630 in healthy participants and participants with asthma will be assessed.

  Until Follow-up (FU) Visit/Early Termination (ET) Visit (Part A: 7-day post-dose for SAD; 10-day post-last dose for MAD) and Part B: Until FU Visit/ET Visit (10-day post-last dose)

• Part A (IV cohort): Time to reach maximum observed concentration (tmax) of AZD8630

  tmax of AZD8630 following IV administration of single dose of AZ8630 in healthy participants will be assessed

  Pre-dose and Post-dose on Days 1 to 4 and Follow-up Visit/ET Visit (7-day post-dose)

• Part A (IV cohort): Time of last observed quantifiable concentration (tlast) of AZD8630

  tlast of AZD8630 following IV administration of single dose of AZ8630 in healthy participants will be assessed

  Pre-dose and Post-dose on Days 1 to 4 and Follow-up Visit/ET Visit (7-day post-dose)

• Part A (IV cohort): Maximum observed serum (peak) drug concentration (Cmax) of AZD8630

  Cmax of AZD8630 following IV administration of single dose of AZ8630 in healthy participants will be assessed.

  Pre-dose and Post-dose on Days 1 to 4 and Follow-up Visit/ET Visit (7-day post-dose)

• Part A (IV cohort): Partial area under the serum concentration-time curve from 0 to time 24 hours post-dose [AUC(0-24)] of AZD8630

  AUC(0-24) of AZD8630 following IV administration of single dose of AZ8630 in healthy participants will be assessed.

  Pre-dose and Post-dose on Days 1 to 4 and Follow-up Visit/ET Visit (7-day post-dose)

• Part A (IV cohort): Area under the serum concentration curve from zero to the last quantifiable concentration (AUClast) of AZD8630

  AUClast of AZD8630 following IV administration of single dose of AZ8630 in healthy participants will be assessed.

  Pre-dose and Post-dose on Days 1 to 4 and Follow-up Visit/ET Visit (7-day post-dose)

• Part A (IV cohort): Area under serum concentration-time curve from zero to infinity (AUCinf) of AZD8630

  AUCinf of AZD8630 following IV administration of single dose of AZ8630 in healthy participants will be assessed.

  Pre-dose and Post-dose on Days 1 to 4 and Follow-up Visit/ET Visit (7-day post-dose)

• Part A (IV cohort): Terminal rate constant (λz) of AZD8630

  λz of AZD8630 following IV administration of single dose of AZ8630 in healthy participants will be assessed.

  Pre-dose and Post-dose on Days 1 to 4 and Follow-up Visit/ET Visit (7-day post-dose)

• Part A (IV cohort): Half-life associated with terminal slope (λz) of a semi-logarithmic concentration-time curve (t1/2λz) of AZD8630

  t1/2λz) of AZD8630 following IV administration of single dose of AZ8630 in healthy participants will be assessed.

  Pre-dose and Post-dose on Days 1 to 4 and Follow-up Visit/ET Visit (7-day post-dose)

• Part A (IV cohort): Mean residence time of the unchanged drug in the systemic circulation (MRTinf) of AZD8630

  MRTinf of AZD8630 following IV administration of single dose of AZ8630 in healthy participants will be assessed.

  Pre-dose and Post-dose on Days 1 to 4 and Follow-up Visit/ET Visit (7-day post-dose)

• Part A (IV cohort): Total body clearance of drug from serum after IV administration (CL) of AZD8630

  CL of AZD8630 following IV administration of single dose of AZ8630 in healthy participants will be assessed.

  Pre-dose and Post-dose on Days 1 to 4 and Follow-up Visit/ET Visit (7-day post-dose)

• Part A (IV cohort): Volume of distribution at steady state (Vss) of AZD8630

  Vss of AZD8630 following IV administration of single dose of AZ8630 in healthy participants will be assessed.

  Pre-dose and Post-dose on Days 1 to 4 and Follow-up Visit/ET Visit (7-day post-dose)

• Part A (IV Cohort): Volume of distribution of drug from serum after IV administration (Vz) of AZD8630

  Vz of AZD8630 following IV administration of single dose of AZ8630 in healthy participants will be assessed.

  Pre-dose and Post-dose on Days 1 to 4 and Follow-up Visit/ET Visit (7-day post-dose)

• Part A (IV Cohort): Number of participants with adverse events

  Safety and tolerability of IV AZD8630 in healthy participants will be assessed.

  Until Follow-up (FU) Visit/Early Termination (ET) Visit (7-day post-dose)

Secondary Outcomes (22)

• Part A and Part B: Time to reach maximum observed concentration (tmax) of AZD8630

  Pre-dose and Post-dose: Part A- (SAD) Days 1 to 4 and FU Visit/ET Visit (7-day post-dose), (MAD) Days 1 to 17 and FU Visit/ET Visit (10-day post-last dose); Part B- Days 1 to 14, Day 28, Day 29, and FU Visit/ ET Visit (10-day post-last dose)

• Part A (A1 and A2 only): Time of last observed quantifiable concentration (tlast) of AZD8630

  Pre-dose and Post-dose: Part A- (SAD) Days 1 to 4 and FU Visit/ET Visit (7-day post-dose)

• Part A and Part B: Maximum observed serum (peak) drug concentration (Cmax) of AZD8630

  Pre-dose and Post-dose: Part A- (SAD) Days 1 to 4 and FU Visit/ET Visit (7-day post-dose), (MAD) Days 1 to 17 and FU Visit/ET Visit (10-day post-last dose); Part B- Days 1 to 14, Day 28, Day 29, and FU Visit/ ET Visit (10-day post-last dose)

• Part A and Part B: Maximum observed serum (peak) drug concentration divided by the lung-delivered dose (LDD) [Cmax/D] of AZD8630

  Pre-dose and Post-dose: Part A- (SAD) Days 1 to 4 and FU Visit/ET Visit (7-day post-dose), (MAD) Days 1 to 17 and FU Visit/ET Visit (10-day post-last dose); Part B- Days 1 to 14, Day 28, Day 29, and FU Visit/ ET Visit (10-day post-last dose)

• Part A and Part B: Concentration at the end of the dosing interval (Ctrough) [repeat dose only] of AZD8630

  Pre-dose and Post-dose: Part A- (MAD) Days 1 to 17 and FU Visit/ET Visit (10-day post-last dose); Part B- Days 1 to 14, Day 28, Day 29, and FU Visit/ ET Visit (10-day post-last dose)

Study Arms (10)

Part A1: SAD (AZD8630)

EXPERIMENTAL

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

Drug: AZD8630

Part A1: IV (AZD8630)

EXPERIMENTAL

Healthy participants will receive a single IV dose of AZD8630.

Drug: AZD8630

Part A1: IV (Placebo)

PLACEBO COMPARATOR

Healthy participants will receive single IV dose of Placebo.

Drug: Placebo

Part A2: SAD (AZD8630)

EXPERIMENTAL

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

Drug: AZD8630

Part A3: MAD (AZD8630)

EXPERIMENTAL

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

Drug: AZD8630

Part A4: MAD (AZD8630)

EXPERIMENTAL

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

Drug: AZD8630

Part A: SAD (Placebo)

PLACEBO COMPARATOR

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

Drug: Placebo

Part A: MAD (Placebo)

PLACEBO COMPARATOR

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

Drug: Placebo

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.

Drug: AZD8630

Part B (Placebo)

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

AZD8630 DRUG

Participants will receive Inhaled or IV doses of AZD8630 as per the arm they are assigned.

Part A1: IV (AZD8630); Part A1: SAD (AZD8630); Part A2: SAD (AZD8630); Part A3: MAD (AZD8630); Part A4: MAD (AZD8630); Part B (AZD8630)

Placebo DRUG

Participants will receive Inhaled or IV doses of placebo as per the arm they are assigned.

Part A1: IV (Placebo); Part A: MAD (Placebo); Part A: SAD (Placebo); Part B (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:

• 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%.

You may not qualify if:

• 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.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (29)

Research Site

Tempe, Arizona, 85283, United States

Location

Research Site

Bakersfield, California, 93301, United States

Location

Research Site

Glendale, California, 91206, United States

Location

Research Site

San Jose, California, 95117, United States

Location

Research Site

Homestead, Florida, 33030, United States

Location

Research Site

Miami, Florida, 33122, United States

Location

Research Site

Miami, Florida, 33144, United States

Location

Research Site

Miami, Florida, 33155, United States

Location

Research Site

Miami, Florida, 33173, United States

Location

Research Site

Miami, Florida, 33175, United States

Location

Research Site

Boise, Idaho, 83706, United States

Location

Research Site

White Marsh, Maryland, 21162, United States

Location

Research Site

North Dartmouth, Massachusetts, 02747, United States

Location

Research Site

Ann Arbor, Michigan, 48105, United States

Location

Research Site

Raleigh, North Carolina, 27607, United States

Location

Research Site

Toledo, Ohio, 43617, United States

Location

Research Site

Portland, Oregon, 97202, United States

Location

Research Site

El Paso, Texas, 79903, United States

Location

Research Site

Berlin, 10119, Germany

Location

Research Site

Frankfurt, 60596, Germany

Location

Research Site

Großhansdorf, 22927, Germany

Location

Research Site

Lübeck, 23552, Germany

Location

Research Site

Magdeburg, 39120, Germany

Location

Research Site

Wiesbaden, 65187, Germany

Location

Research Site

Bradford, BD9 6RJ, United Kingdom

Location

Research Site

London, HA1 3UJ, United Kingdom

Location

Research Site

London, W12 0HS, United Kingdom

Location

Research Site

Manchester, M23 9QZ, United Kingdom

Location

Research Site

Portsmouth, PO6 3LY, United Kingdom

Location

MeSH Terms

Conditions

Asthma

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Part A of the study is single-blind, and Part B of the study is double-blind
• Purpose: OTHER
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 28, 2021
• First Posted: November 8, 2021
• Study Start: December 16, 2021
• Primary Completion: August 2, 2023
• Study Completion: August 2, 2023
• Last Updated: August 30, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will share
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please refer to our disclosure commitment at: https://astrazenecagrouptrials.pharmacm.com /ST/Submission/Disclosure.
• Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patientlevel data in an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at: https://astrazenecagrouptrials.pharmacm.com /ST/Submission/Disclosure.

Locations

GB (5); DE (6); US (18)