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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT04643158




Registration number
NCT04643158
Ethics application status
Date submitted
23/11/2020
Date registered
24/11/2020
Date last updated
16/08/2023

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
Terminated
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
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT04643158
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



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT04643158