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Clinical Trial Details — Status: Terminated

Administrative data

NCT number NCT04643158
Other study ID # D2912C00003
Secondary ID 2020-002828-37
Status Terminated
Phase Phase 2
First received
Last updated
Start date March 12, 2021
Est. completion date July 20, 2023

Study information

Verified date August 2023
Source AstraZeneca
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

This is a randomised, placebo-controlled, double-blinded, multi-centre, 2-part study to assess the efficacy and safety of inhaled AZD1402. Part 1 will be performed in a Lead-in Cohort for each dose level to evaluate the safety and pharmacokinetics (PK) in a population with asthma controlled on medium dose inhaled corticosteroids (ICS)-long acting beta agonists (LABA) before progressing to dosing in adults with asthma who are uncontrolled on medium-to-high dose ICS-LABA in Part 2. The study will recruit participants receiving treatment with medium dose ICS with LABA for Part 1 and participants receiving treatment with medium-to-high dose ICS with LABA for Part 2 (separate inhalers or combination product). Part 2 will be initiated following evaluation of safety and PK at the relevant dose level in Part 1a. The entire study period for each participant in both Parts 1 and 2, is approximately 3.5 months; a 2-week Screening Period, a 4 week Run-in Period, 4 weeks of Treatment Period, and 4 weeks of Follow-Up Period.


Description:

Part 1 of the study will be randomised, double blind, placebo-controlled, and conducted in parallel for the 2 lower dose levels (Part 1a) followed by an unblinded safety review and escalation to the highest dose (Part 1b) dependent on the outcome of the safety review. Part 1a will consist of 30 participants who will be randomised 1:1:1 to receive 1 of the 2 lower AZD1402 dry power inhaler (DPI) doses (Dose 1 or Dose 2) or placebo in parallel. Part 1b will consist of 15 participants who will be randomised 2:1 to receive the highest AZD1402 DPI dose (Dose 3) or placebo. Part 1a Lead-in Cohort - AZD1402 Dose 1 - AZD1402 Dose 2 - Placebo Part 1b Lead-in Cohort - AZD1402 Dose 3 - Placebo Part 2 will be randomised, double blind, placebo controlled and will include approximately 165 participants randomised 2:1 (active to placebo) to evaluate 2 inhaled dose levels of AZD1402 versus placebo. Part 2 will be started after the unblinded safety review for Part 1a. Part 2 will include: - AZD1402 Dose 1 - AZD1402 Dose 2 - Placebo


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Study Design


Related Conditions & MeSH terms


Intervention

Drug:
AZD1402
Randomised participants will receive oral inhalation of AZD1402, via DPI.
Placebo
Randomised participants will receive oral inhalation of matching placebo via DPI.
Short acting beta agonist (SABA) (rescue medication)
In addition to study intervention, all participants will be provided with a SABA as rescue medication (eg, salbutamol/albuterol), to be used throughout the Run-in and Treatment Periods. All participants should refrain from taking a SABA as rescue medication 6 hours prior to pulmonary function tests. Dosage levels: 100 µg per nominal dose 90 µg per nominal dose pro re nata (as required) (PRN)
Run-in medications (ICS-LABA combination)
During the Run-in Period, the participants are required to maintain on their ICS-LABA dose. Controller medications (eg, ICS LABA) should remain at a stable dose and be taken after study intervention as applicable. These drugs are used as standard of care.

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Sponsors (1)

Lead Sponsor Collaborator
AstraZeneca

Countries where clinical trial is conducted

Australia,  Canada,  Germany,  Hungary,  Korea, Republic of,  Poland,  Spain,  Taiwan,  Ukraine,  United Kingdom, 

Outcome

Type Measure Description Time frame Safety issue
Primary Part 1: Number of participants with adverse events (AEs) To evaluate the safety and tolerability of AZD1402 compared to placebo at different dose levels in adults with asthma controlled on medium dose ICS-LABA. Safety and tolerability variables included AEs/ adverse events of special interest (AESIs) / serious adverse events (SAEs), vital signs (blood pressure and pulse rate), changes in clinical chemistry, haematology, and coagulation parameters, Immuno-biomarkers, Electrocardiograms (ECGs), Forced expiratory volume in 1 second (FEV1) and fractional exhaled nitric oxide (FeNO). From Day 1 until Follow-up (Day 56 ± 4)
Primary Part 2: Change from baseline in pre-bronchodilator FEV1 at Week 4 To investigate the efficacy of inhaled AZD1402 compared to placebo in adults with asthma who are uncontrolled on medium-to-high dose ICS-LABA. Baseline and Week 4
Secondary Part 1 and Part 2: Maximum observed serum (peak) drug concentration (Cmax) To investigate the PK profile of AZD1402 (Part 1: full profile in all participants; Part 2: sparse in all, full profile in a subset of participants in each treatment arm). Day 1 until Day 56 ± 4
Secondary Part 1 and Part 2: Time to reach peak or maximum observed concentration or response following drug administration (tmax) To investigate the PK profile of AZD1402 (Part 1: full profile in all participants; Part 2: sparse in all, full profile in a subset of participants in each treatment arm). Day 1 until Day 56 ± 4
Secondary Part 1 and Part 2: Observed lowest drug concentration reached before the next dose is administered (pre-dose) (Ctrough) To investigate the PK profile of AZD1402 (Part 1: full profile in all participants; Part 2: sparse in all, full profile in a subset of participants in each treatment arm). Day 1 until Day 56 ± 4
Secondary Part 1 and Part 2: Terminal rate constant, estimated by log-linear least squares regression of the terminal part of the concentration-time curve (?z) To investigate the PK profile of AZD1402 (Part 1: full profile in all participants; Part 2: sparse in all, full profile in a subset of participants in each treatment arm). Day 1 until Day 56 ± 4
Secondary Part 1 and Part 2: Half-life associated with terminal slope (?z) of a semi-logarithmic concentration-time curve (t1/2?z) To investigate the PK profile of AZD1402 (Part 1: full profile in all participants; Part 2: sparse in all, full profile in a subset of participants in each treatment arm). Day 1 until Day 56 ± 4
Secondary Part 1 and Part 2: Area under the plasma concentration-curve from zero to the last quantifiable concentration (AUClast) To investigate the PK profile of AZD1402 (Part 1: full profile in all participants; Part 2: sparse in all, full profile in a subset of participants in each treatment arm). Day 1 until Day 56 ± 4
Secondary Part 1 and Part 2: Area under plasma concentration-time curve in the dosing interval (AUCt) To investigate the PK profile of AZD1402 (Part 1: full profile in all participants; Part 2: sparse in all, full profile in a subset of participants in each treatment arm). Day 1 until Day 56 ± 4
Secondary Part 1 and Part 2: Apparent total body clearance of drug from plasma after extravascular administration (CL/F) To investigate the PK profile of AZD1402 (Part 1: full profile in all participants; Part 2: sparse in all, full profile in a subset of participants in each treatment arm). Day 1 until Day 56 ± 4
Secondary Part 1 and Part 2: Volume of distribution (apparent) at steady state following extravascular administration (based on terminal phase) (Vz/F) To investigate the PK profile of AZD1402 (Part 1: full profile in all participants; Part 2: sparse in all, full profile in a subset of participants in each treatment arm). Day 1 until Day 56 ± 4
Secondary Part 1 and Part 2: Area under the plasma concentration time curve in the dosing interval t divided by the dose administered (Dose normalised AUCt) To investigate the PK profile of AZD1402 (Part 1: full profile in all participants; Part 2: sparse in all, full profile in a subset of participants in each treatment arm). Day 1 until Day 56 ± 4
Secondary Part 1 and Part 2: Maximum observed plasma (peak) drug concentration divided by the dose administered (Dose normalised Cmax) To investigate the PK profile of AZD1402 (Part 1: full profile in all participants; Part 2: sparse in all, full profile in a subset of participants in each treatment arm). Day 1 until Day 56 ± 4
Secondary Part 1 and Part 2: Time of last observed (quantifiable) concentration (tlast) To investigate the PK profile of AZD1402 (Part 1: full profile in all participants; Part 2: sparse in all, full profile in a subset of participants in each treatment arm). Day 1 until Day 56 ± 4
Secondary Part 1 and Part 2: Accumulation ratio for AUCt (Rac AUC) To investigate the PK profile of AZD1402 (Part 1: full profile in all participants; Part 2: sparse in all, full profile in a subset of participants in each treatment arm). Day 1 until Day 56 ± 4
Secondary Part 1 and Part 2: Accumulation ratio for Cmax (Rac Cmax) To investigate the PK profile of AZD1402 (Part 1: full profile in all participants; Part 2: sparse in all, full profile in a subset of participants in each treatment arm). Day 1 until Day 56 ± 4
Secondary Part 1 and Part 2: Antidrug antibodies (ADA) titers testing for all ADA-positive samples as measure of immunogenicity To investigate the immunogenicity of AZD1402. Day 1 until Day 56 ± 4
Secondary Part 2: Change from baseline in pre bronchodilator FEV1 average over the 4-week Treatment Period To further investigate the efficacy of AZD1402 compared to placebo in adults with asthma who are uncontrolled on medium-to-high dose ICS-LABA. Baseline, 4 weeks
Secondary Part 2: Change from baseline in Asthma control questionnaire-6 (ACQ-6) at Week 4 and average over the Treatment Period To further investigate the efficacy of AZD1402 compared to placebo in adults with asthma who are uncontrolled on medium-to-high dose ICS-LABA. The ACQ was developed to measure asthma control. In the ACQ-6, participants will be asked to recall how their asthma has been during the previous week by responding to one bronchodilation use question and 5 symptom questions. Questions are weighted equally and scored from 0 (totally controlled) to 6 (severely uncontrolled). Higher scores indicated worse outcome. The mean ACQ-6 score is the mean of the responses. Mean scores of = 0.75 indicate well-controlled asthma, scores between 0.75 and = 1.5 indicate partly controlled asthma, and scores > 1.5 indicate not well-controlled asthma. Individual changes of at least 0.5 are considered clinically meaningful. Baseline, Week 4
Secondary Part 2: Proportion of participants with a decrease in ACQ 6 score of = 0.5 from baseline to Week 4 To further investigate the efficacy of AZD1402 compared to placebo in adults with asthma who are uncontrolled on medium-to-high dose ICS-LABA. The ACQ was developed to measure asthma control. In the ACQ-6, participants will be asked to recall how their asthma has been during the previous week by responding to one bronchodilation use question and 5 symptom questions. Questions are weighted equally and scored from 0 (totally controlled) to 6 (severely uncontrolled). Higher scores indicated worse outcome. The mean ACQ-6 score is the mean of the responses. Mean scores of = 0.75 indicate well-controlled asthma, scores between 0.75 and = 1.5 indicate partly controlled asthma, and scores > 1.5 indicate not well-controlled asthma. Individual changes of at least 0.5 are considered clinically meaningful. Baseline, Week 4
Secondary Part 2: Change from baseline in average morning Peak expiratory flow (PEF) over the Treatment Period To further investigate the efficacy of AZD1402 compared to placebo in adults with asthma who are uncontrolled on medium-to-high dose ICS-LABA. Peak expiratory flow will be measured by the participant at home using a peak flow meter. Baseline, 4 weeks
Secondary Part 2: Change from baseline in average evening PEF over the Treatment Period To further investigate the efficacy of AZD1402 compared to placebo in adults with asthma who are uncontrolled on medium-to-high dose ICS-LABA. Peak expiratory flow will be measured by the participant at home using a peak flow meter. Baseline, 4 weeks
Secondary Part 2: Change from baseline in daily average asthma symptom score (AM/PM) over the Treatment Period To further investigate the efficacy of AZD1402 compared to placebo in adults with asthma who are uncontrolled on medium-to-high dose ICS-LABA. Severity scores for asthma symptoms will be recorded twice daily in the morning and evening and documented in the e-Diary. Asthma symptom scores during night-time and day-time will be assessed by the participant each morning and evening according to the following scoring system:
0: You have no asthma symptoms.
You are aware of your asthma symptoms but you can easily tolerate the symptoms.
Your asthma is causing you enough discomfort to cause problems with normal activities (or with sleep).
You are unable to do your normal activities (or to sleep) because of your asthma.
Higher scores indicated worse outcome.
Baseline, 4 weeks
Secondary Part 2: Change from baseline in fractional exhaled nitric oxide (FeNO) (in-clinic) at Week 4 and average over the Treatment Period To investigate the effect of AZD1402 compared to placebo on airway inflammation in adults with asthma who are uncontrolled on medium-to-high dose ICS-LABA. To investigate the effect of AZD1402 on airway inflammation, the measurement of FeNO will be performed in accordance with ATS/ERS guidelines. Standardised conditions with regard to exhalation flow rate and duration of exhalation will be followed such that plateau definition can be evaluated over a minimum of 3 seconds. The concentration of FeNO will be measured in units of part per billion (ppb). Baseline, Week 4
Secondary Part 2: Number of participants with adverse events (AEs) To evaluate the safety and tolerability of AZD1402 compared to placebo in adults with asthma who are uncontrolled on medium-to-high dose ICS-LABA. Safety and tolerability variables included AEs/AESIs/SAEs, vital signs (blood pressure and pulse rate), changes in clinical chemistry, haematology, and coagulation parameters, Immuno-biomarkers, ECGs, FEV1 and FeNO. From Day 1 until the Follow-up (Day 56 ± 4)
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