A Study to Evaluate the Effect of AZD8154 Administered Via Nebulizer Once Daily in Subjects With Mild Allergic Asthma Challenged With an Inhaled Allergen

NCT04187508 | Withdrawn Phase 2

• 1 other identifier: D8900C00004
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 5

Brief Summary

This is a Phase IIa, double blind, randomized, parallel group, placebo controlled multi centre study to evaluate the effect of AZD8154 (administered via nebulizer daily \[QD\]) on allergen-induced inflammation in subjects with mild allergic asthma challenged with an inhaled allergen. Approximately 36 subjects who meet all eligibility criteria will be randomized (1:1) to receive either AZD8154 or placebo.

Conditions

Asthma

Keywords

Allergen-induced inflammation

Outcome Measures

Primary Outcomes (2)

• Maximal percentage decrease in forced expiratory volume in 1 second (FEV1) 3-7 hours post-allergen challenge

  To evaluate the effect of AZD8154 on the allergen-induced late asthmatic response 3-7 hours post-allergen challenge (LAR3-7hr) when compared with placebo

  At day 9

• Area under the curve (AUC) of time adjusted percent decrease in FEV1 in late asthmatic response (LAR) 3-7hr

  To evaluate the effect of AZD8154 on the allergen-induced late asthmatic response 3-7 hours post-allergen challenge (LAR3-7hr) when compared with placebo

  At day 9

Secondary Outcomes (6)

• Maximum percentage fall in FEV1 0-2 hours post-allergen challenge

  At day 9

• AUC of time adjusted percent decrease in FEV1 curve in EAR0-2hr

  At day 9

• PC20 dose of methacholine causing ≥20% fall in FEV1

  At Day 1, Day 8 and Day 10

• FENO at baseline, pre-allergen challenge and at 7 and 24 hours post-allergen challenge

  At Day 1, Day 8, Day 9 and Day 10

• Plasma concentrations of AZD8154 pre- and post-allergen challenge

  At pre-dose on day 1, day 2 to day 7, 10 minutes post-dose on day 8 and pre-dose and 1, 2, 4 and 8 hours post-dose on day 9, pre-dose on day 10 and day 17 (follow-up)

Study Arms (2)

AZD8154

EXPERIMENTAL

Subjects will receive AZD8154 QD dosing for 10 days

Drug: AZD8154 nebulizer suspension, 20 mg/mL

Placebo

PLACEBO COMPARATOR

Subjects will receive AZD8154 matching placebo QD dosing for 10 days

Drug: Placebo

Interventions

AZD8154 nebulizer suspension, 20 mg/mL DRUG

Subjects will receive AZD8154 from Day 1 to Day 10 (10 consecutive days) by using nebulizer and dosimeter system as inhaled dosing and delivered dose will be 3mg.

AZD8154

Placebo DRUG

Subjects will receive AZD8154 matching placebo (placebo nebulizer suspension, glucose solution for infusion 50 mg/mL) QD from Day 1 to Day 10 (10 consecutive days) by using nebulizer and dosimeter system as inhaled dosing.

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Informed consent
• Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this Clinical Study Protocol (CSP).
• Provision of signed and dated, written ICF prior to any mandatory study specific procedures, sampling, and analyses.
• Provision of signed and dated written Genetic ICF prior to collection of samples for genetic analysis (if subject agrees to take part in this optional assessment).
• Age • Subject must be 18 to 65 years of age (inclusive) at the time of signing the ICF.
• Type of subject and disease characteristics
• Individuals who are determined as healthy by the Investigator, based on medical evaluations including, but not limited to, medical history, physical examination, laboratory tests, vital signs, and electrocardiogram (ECG).
• Subjects have mild, stable, allergic asthma with episodic wheeze and shortness of breath. Asthma therapy is limited to inhaled, short-acting β2 agonists (should not be used on more than 2 occasions in a week, excluding for prophylactic treatment).
• Subjects have no current exposure to allergens to which the subject experiences asthmatic responses (except for the house dust mite).
• Positive methacholine challenge (PC20 ≤16 mg/mL) at screening (Visit 2).
• Positive skin-prick test to at least one common aeroallergen at screening (Visit 1).
• Positive early and late airway responses during the screening allergen challenge. The EAR will be a fall in FEV1 of ≥20% during the 2 hours after allergen challenge. The LAR will be defined as a fall in FEV1 of ≥15% during the 3-7 hours after allergen challenge.
• Pre-bronchodilator FEV1 at screening (Visit 1) ≥70% of predicted normal value.
• Weight
• Body mass index (BMI) within the range 18 to 35 kg/m2 (inclusive).

You may not qualify if:

• Medical conditions
• A worsening of asthma or a respiratory tract infection from 6 weeks prior to Visit 1 or during the screening period, requiring a change of treatment.
• Any history of life-threatening asthma attack or asthma attack requiring admission to an intensive care unit and/or ventilation.
• A medical history or evidence of medical conditions which in the Investigator's opinion makes it undesirable for the subject to participate in the study, including but not limited to:
• lung disease (excluding sleep apnea) other than mild allergic asthma
• history of diabetes, metabolic syndrome, Gilbert syndrome, hepatic impairment, hypertriglyceridemia, or familial lipid disorders
• clinically significant hypotensive episodes or symptoms of fainting, dizziness, or light headedness
• cardiovascular disease, particularly coronary artery disease, hypertension, congestive heart failure or any clinically important abnormalities in rhythm, conduction or morphology of the ECG at rest that may interfere with the interpretation of QT interval corrected (QTc) interval changes.
• significant neurologic disease, including transient ischemic attack, stroke, or seizure disorder
• alcoholism, drug dependency or abuse
• latent or chronic infection (eg, recurrent sinusitis, genital or ocular herpes, urinary tract infection) or at risk of infection (eg, surgery) within 90 days of screening
• malignancy in the previous 5 years other than superficial basal cell carcinoma.
• Prolonged QT interval corrected using Fridericia's formula (QTcF) \>450 milliseconds (ms) based on ECG (at Visit 1 or Visit 6 pre-dose) or family history of long QT syndrome
• Persistent or intermittent bundle branch block, intermittent second or third degree atrial ventricular (AV) block or AV dissociation (at Visit 1 or Visit 6).
• Current smokers. Ex-smokers must not have smoked or used nicotine or cannabis products (including e-cigarettes) for a minimum of 6 months prior to enrolment and should not have a smoking history ≥10 pack years.

Sponsors & Collaborators

• AstraZeneca: lead
• Parexel: collaborator

Study Sites (5)

Research Site

Calgary, Alberta, T2N 4Z6, Canada

Location

Research Site

Edmonton, Alberta, T6G 2G3, Canada

Location

Research Site

Vancouver, British Columbia, V5Z 1M9, Canada

Location

Research Site

Hamilton, Ontario, L8N 3Z5, Canada

Location

Research Site

Saskatoon, Saskatchewan, S7N 0W8, Canada

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 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: The study will be randomized and double blinded, ie, subjects, Investigators, and other study site personnel must be kept blinded to avoid bias, although due to the differences between the AZD8154 and placebo treatments unblinded pharmacy/site staff will be required for dose preparation and administration.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 3, 2019
• First Posted: December 5, 2019
• Study Start: February 6, 2020
• Primary Completion: November 10, 2021
• Study Completion: November 10, 2021
• Last Updated: November 3, 2020

Record last verified: 2020-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• 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 rerefer 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 deidentified individual patient-level 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

CA (5)