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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04643158




Registration number
NCT04643158
Ethics application status
Date submitted
23/11/2020
Date registered
24/11/2020

Titles & IDs
Public title
Efficacy and Safety of Inhaled AZD1402 Administered for Four Weeks in Adults With Asthma on Medium-to-High Dose Inhaled Corticosteroids
Scientific title
A Two-part Phase IIa Randomised, Double-blind, Placebo-controlled, Dose-ranging, Multi-centre Study to Assess Efficacy and Safety of Inhaled AZD1402 Administered as a Dry Powder for Four Weeks in Adults With Asthma on Medium-to-High Dose Inhaled Corticosteroids
Secondary ID [1] 0 0
2020-002828-37
Secondary ID [2] 0 0
D2912C00003
Universal Trial Number (UTN)
Trial acronym
APATURA
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Asthma 0 0
Condition category
Condition code
Respiratory 0 0 0 0
Asthma
Respiratory 0 0 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - AZD1402
Treatment: Drugs - Placebo
Treatment: Drugs - Short acting beta agonist (SABA) (rescue medication)
Treatment: Drugs - Run-in medications (ICS-LABA combination)

Experimental: Part 1 and Part 2: AZD1402 Dose 1 - Randomised participants will receive oral inhalation of AZD1402 Dose 1 via DPI.

Experimental: Part 1 and Part 2: AZD1402 Dose 2 - Randomised participants will receive oral inhalation of AZD1402 Dose 2 via DPI.

Experimental: Part 1: AZD1402 Dose 3 - Randomised participants will receive oral inhalation of AZD1402 Dose 3 via DPI.

Placebo comparator: Part 1 and Part 2: Placebo - Randomised participants will receive oral inhalation of matching placebo via DPI.


Treatment: Drugs: AZD1402
Randomised participants will receive oral inhalation of AZD1402, via DPI.

Treatment: Drugs: Placebo
Randomised participants will receive oral inhalation of matching placebo via DPI.

Treatment: Drugs: 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)

Treatment: Drugs: 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.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Part 1: Number of participants with adverse events (AEs)
Timepoint [1] 0 0
From Day 1 until Follow-up (Day 56 ± 4)
Primary outcome [2] 0 0
Part 2: Change from baseline in pre-bronchodilator FEV1 at Week 4
Timepoint [2] 0 0
Baseline and Week 4
Secondary outcome [1] 0 0
Part 1 and Part 2: Maximum observed serum (peak) drug concentration (Cmax)
Timepoint [1] 0 0
Day 1 until Day 56 ± 4
Secondary outcome [2] 0 0
Part 1 and Part 2: Time to reach peak or maximum observed concentration or response following drug administration (tmax)
Timepoint [2] 0 0
Day 1 until Day 56 ± 4
Secondary outcome [3] 0 0
Part 1 and Part 2: Observed lowest drug concentration reached before the next dose is administered (pre-dose) (Ctrough)
Timepoint [3] 0 0
Day 1 until Day 56 ± 4
Secondary outcome [4] 0 0
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)
Timepoint [4] 0 0
Day 1 until Day 56 ± 4
Secondary outcome [5] 0 0
Part 1 and Part 2: Half-life associated with terminal slope (?z) of a semi-logarithmic concentration-time curve (t1/2?z)
Timepoint [5] 0 0
Day 1 until Day 56 ± 4
Secondary outcome [6] 0 0
Part 1 and Part 2: Area under the plasma concentration-curve from zero to the last quantifiable concentration (AUClast)
Timepoint [6] 0 0
Day 1 until Day 56 ± 4
Secondary outcome [7] 0 0
Part 1 and Part 2: Area under plasma concentration-time curve in the dosing interval (AUCt)
Timepoint [7] 0 0
Day 1 until Day 56 ± 4
Secondary outcome [8] 0 0
Part 1 and Part 2: Apparent total body clearance of drug from plasma after extravascular administration (CL/F)
Timepoint [8] 0 0
Day 1 until Day 56 ± 4
Secondary outcome [9] 0 0
Part 1 and Part 2: Volume of distribution (apparent) at steady state following extravascular administration (based on terminal phase) (Vz/F)
Timepoint [9] 0 0
Day 1 until Day 56 ± 4
Secondary outcome [10] 0 0
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)
Timepoint [10] 0 0
Day 1 until Day 56 ± 4
Secondary outcome [11] 0 0
Part 1 and Part 2: Maximum observed plasma (peak) drug concentration divided by the dose administered (Dose normalised Cmax)
Timepoint [11] 0 0
Day 1 until Day 56 ± 4
Secondary outcome [12] 0 0
Part 1 and Part 2: Time of last observed (quantifiable) concentration (tlast)
Timepoint [12] 0 0
Day 1 until Day 56 ± 4
Secondary outcome [13] 0 0
Part 1 and Part 2: Accumulation ratio for AUCt (Rac AUC)
Timepoint [13] 0 0
Day 1 until Day 56 ± 4
Secondary outcome [14] 0 0
Part 1 and Part 2: Accumulation ratio for Cmax (Rac Cmax)
Timepoint [14] 0 0
Day 1 until Day 56 ± 4
Secondary outcome [15] 0 0
Part 1 and Part 2: Antidrug antibodies (ADA) titers testing for all ADA-positive samples as measure of immunogenicity
Timepoint [15] 0 0
Day 1 until Day 56 ± 4
Secondary outcome [16] 0 0
Part 2: Change from baseline in pre bronchodilator FEV1 average over the 4-week Treatment Period
Timepoint [16] 0 0
Baseline, 4 weeks
Secondary outcome [17] 0 0
Part 2: Change from baseline in Asthma control questionnaire-6 (ACQ-6) at Week 4 and average over the Treatment Period
Timepoint [17] 0 0
Baseline, Week 4
Secondary outcome [18] 0 0
Part 2: Proportion of participants with a decrease in ACQ 6 score of = 0.5 from baseline to Week 4
Timepoint [18] 0 0
Baseline, Week 4
Secondary outcome [19] 0 0
Part 2: Change from baseline in average morning Peak expiratory flow (PEF) over the Treatment Period
Timepoint [19] 0 0
Baseline, 4 weeks
Secondary outcome [20] 0 0
Part 2: Change from baseline in average evening PEF over the Treatment Period
Timepoint [20] 0 0
Baseline, 4 weeks
Secondary outcome [21] 0 0
Part 2: Change from baseline in daily average asthma symptom score (AM/PM) over the Treatment Period
Timepoint [21] 0 0
Baseline, 4 weeks
Secondary outcome [22] 0 0
Part 2: Change from baseline in fractional exhaled nitric oxide (FeNO) (in-clinic) at Week 4 and average over the Treatment Period
Timepoint [22] 0 0
Baseline, Week 4
Secondary outcome [23] 0 0
Part 2: Number of participants with adverse events (AEs)
Timepoint [23] 0 0
From Day 1 until the Follow-up (Day 56 ± 4)

Eligibility
Key inclusion criteria
* Participants who have a documented clinical diagnosis of asthma for = 12 months before Visit 1.
* Participants who are able to perform acceptable pulmonary function testing for FEV1.
* Participants who are able to demonstrate the ability to use the study inhalation device properly.
* Male participants must be surgically sterile or agree to use highly-effective contraceptives.
* All female participants must have a negative serum pregnancy test at Screening. Female participants of non-childbearing potential, Female participants of childbearing potential must have a negative urine pregnancy test before the administration of first dose of study intervention and must agree to use a highly-effective method of birth control.
* Participant is a non smoker or an ex-smoker with a total smoking history of less than 10 pack-years.
* Only for Part 1: Documented treatment with medium dose ICS with LABA for at least 6 months prior to Screening. ICS and LABA must be on a stable dose for at least 3 months prior to Screening, during Screening and Run-in Periods and may be contained in a combination product or separate inhaler. No asthma exacerbations in last 12 months requiring oral or intravenous (IV) steroids or hospitalisation/ emergency room visit due to asthma. Pre-bronchodilator FEV1 = 70% predicted at Screening and start of Run-in. Asthma Control Questionnaire 6 score of = 1.0 at Screening and start of Run-in.
* Only for Part 2: Documented evidence of asthma. Documented treatment with medium-to-high dose ICS-LABA for at least 6 months prior to Screening. ICS and LABA must be on a stable dose for at least 4 weeks prior to Screening, during Screening and Run-in Periods. If on asthma maintenance controller medications in addition to ICS-LABA, the dose of the additional controller medications must be stable for at least 4 weeks prior to Screening, during Screening and Run-in Periods. Pre bronchodilator FEV1 of 40% to 85% (inclusive) predicted at Screening and start of Run-in. Blood eosinophil count of = 150 cells/µL and FeNO = 25 ppb at Screening. Asthma Control Questionnaire 6 score = 1.5 at Screening.

Specific Randomisation Criteria at Visit 3

* For Part 1: Pre-bronchodilator FEV1 = 70% predicted. At least 70% compliance with usual asthma controller ICS-LABA during Run-in Period (from Visit 2 to Visit 3) based on daily electronic diary (e-Diary). Minimum 80% compliance with ePRO completion. Asthma Control Questionnaire 6 score of = 1.0. C-reactive protein < 5 mg/L on Day -1.
* For Part 2: Pre-bronchodilator FEV1 of 40% to 85% (inclusive) predicted. Asthma Control Questionnaire 6 score of = 1.5. At least 70% compliance with usual asthma controller ICS-LABA during Run-in Period from (Visit 2 to Visit 3) based on daily e-Diary. Minimum 70% compliance with ePRO completion. C-reactive protein < 10 mg/L at Visit 2. A FeNO of = 25 ppb.
Minimum age
18 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Women who are pregnant or breastfeeding, or who are planning to become pregnant during the study.
* Known or suspected hypersensitivity including anaphylaxis/anaphylactoid reaction following any biologic therapy, or known history of drug hypersensitivity to any component of the study intervention formulation.
* Evidence of any active clinically important pulmonary disease other than asthma, within 5 years at screening.
* History of pulmonary or systemic disease, other than asthma, that are associated with elevated peripheral eosinophil counts.
* History or clinical suspicion of any clinically relevant or active disease or disorder.
* History of severe COVID-19 infection requiring hospitalisation within the last 12 months or clinical history compatible with long COVID (symptoms beyond 12 weeks of acute infection).
* Confirmed symptomatic COVID-19 infection during Screening, Run-in or prior to randomisation.
* Current malignancy or history of malignancy.
* Significant history of recurrent or ongoing 'dry eye'.
* Diagnosis of Sjögren's syndrome.
* High risk of infection suggesting abnormal immune function.
* History of, or known significant infection or positivity at Screening period, including hepatitis B or C, or human immunodeficiency virus (HIV).
* Evidence of active tuberculosis.
* Clinically significant lower respiratory tract infection not resolved within 4 weeks prior to Screening and during Run-in.
* Clinically significant upper respiratory tract infection at Screening and during Run-in.
* A helminth parasitic infection diagnosed within 24 weeks prior to the date informed consent is obtained.
* Any clinically important ECG abnormalities.
* Any clinically significant cardiac disease.
* Uncontrolled hypertension.
* History of life-threatening asthma attack or asthma attack requiring ventilation.
* Part 2 only: History of 3 or more severe asthma exacerbations.
* Daily rescue use of SABA = 8 puffs for = 3 consecutive days at any time during Run-in Period, before randomisation.
* History of anaphylaxis.
* Any clinically significant abnormalities in haematology.
* Alanine aminotransferase or AST level = 3 times the upper limit of normal (ULN), confirmed by repeated testing during Screening Period.
* History of, drug or alcohol abuse within the past 2 years prior to Screening.
* Planned in-patient surgery, major dental procedure or hospitalisation during the study.
* Prior/Concomitant Therapy: Systemic corticosteroid use, AZD1402, marketed or investigational biologicals such as monoclonal antibodies or chimeric biomolecules, investigational nonbiologic drug within 60 days prior to Screening and during Run-in, any immunosuppressive therapy, Live or attenuated vaccine within 4 weeks of Screening and during Run-in, Receipt of COVID-19 vaccine (vaccine or booster dose) within 30 days prior to randomisation, Immunoglobulin or blood products within 4 weeks of Screening and during Run-in, Any immunotherapy within 3 months of Screening and during Run-in.
* Part 1 only: Additional asthma maintenance controller medications in addition to ICS-LABA (eg, leukotriene receptor inhibitors, theophylline, LAMA, chromones) within 3 months of Screening period and during Run-in.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
12/03/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
20/07/2023
Sample size
Target
Accrual to date
Final
72
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Research Site - Herston
Recruitment hospital [2] 0 0
Research Site - Melbourne
Recruitment hospital [3] 0 0
Research Site - Nedlands
Recruitment postcode(s) [1] 0 0
4006 - Herston
Recruitment postcode(s) [2] 0 0
IC 3004 - Melbourne
Recruitment postcode(s) [3] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
Canada
State/province [1] 0 0
Ontario
Country [2] 0 0
Canada
State/province [2] 0 0
Quebec
Country [3] 0 0
Germany
State/province [3] 0 0
Berlin
Country [4] 0 0
Germany
State/province [4] 0 0
Bonn
Country [5] 0 0
Germany
State/province [5] 0 0
Frankfurt
Country [6] 0 0
Germany
State/province [6] 0 0
Hamburg
Country [7] 0 0
Germany
State/province [7] 0 0
Hannover
Country [8] 0 0
Germany
State/province [8] 0 0
Lübeck
Country [9] 0 0
Hungary
State/province [9] 0 0
Szombathely
Country [10] 0 0
Korea, Republic of
State/province [10] 0 0
Cheongiu
Country [11] 0 0
Korea, Republic of
State/province [11] 0 0
Incheon
Country [12] 0 0
Korea, Republic of
State/province [12] 0 0
Namdong-gu
Country [13] 0 0
Korea, Republic of
State/province [13] 0 0
Seoul
Country [14] 0 0
Korea, Republic of
State/province [14] 0 0
Suwon-si
Country [15] 0 0
Poland
State/province [15] 0 0
Bialystok
Country [16] 0 0
Poland
State/province [16] 0 0
Krakow
Country [17] 0 0
Poland
State/province [17] 0 0
Lodz
Country [18] 0 0
Poland
State/province [18] 0 0
Lubin
Country [19] 0 0
Poland
State/province [19] 0 0
Sopot
Country [20] 0 0
Poland
State/province [20] 0 0
Wroclaw
Country [21] 0 0
Spain
State/province [21] 0 0
Barcelona
Country [22] 0 0
Spain
State/province [22] 0 0
Santiago de Compostela
Country [23] 0 0
Spain
State/province [23] 0 0
Villarreal (Castellón)
Country [24] 0 0
Taiwan
State/province [24] 0 0
Kaohsiung
Country [25] 0 0
Ukraine
State/province [25] 0 0
Kiev
Country [26] 0 0
United Kingdom
State/province [26] 0 0
High Wycombe
Country [27] 0 0
United Kingdom
State/province [27] 0 0
Liverpool
Country [28] 0 0
United Kingdom
State/province [28] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
AstraZeneca
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal.

All request will be evaluated as per the AZ disclosure commitment:

https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

Supporting document/s available: Study protocol, Statistical analysis plan (SAP)
When will data be available (start and end dates)?
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.
Available to whom?
When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in a sponsor approved 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.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://astrazenecagroup-dt.pharmacm.com/DT/Home


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT04643158