Study to Assess the Effectiveness and Safety of AZD4604 in Adult Patients with Uncontrolled Moderate-to-Severe Asthma – The AJAX Study
Scientific Title of Study
A Phase 2a Randomised, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of AZD4604 Twice Daily for Twelve Weeks in Adult Patients with Moderate-to-Severe Asthma Uncontrolled on Medium-High Dose ICS-LABA
Trial Acronym
AJAX
Secondary IDs if Any
Secondary ID
Identifier
D8210C00003 VERSION 1.0 Date 01 Jun 2023
Protocol Number
NCT06020014
ClinicalTrials.gov
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Dr Santosh Kadam
Designation
Director, SMM BioPharmaceuticals
Affiliation
AstraZeneca Pharma India Ltd,
Address
Block N1, 12th Floor, Manyata Embassy Business Park, Rachenahalli, Outer Ring Road
Bangalore KARNATAKA 560045 India
Phone
9535999494
Fax
Email
santosh.kadam@astrazeneca.com
Details of Contact Person Scientific Query
Name
Dr Santosh Kadam
Designation
Director, SMM BioPharmaceuticals
Affiliation
AstraZeneca Pharma India Limited
Address
Block N1, 12th Floor, Manyata Embassy Business Park, Rachenahalli, Outer Ring Road
Bangalore KARNATAKA 560045 India
Phone
9535999494
Fax
Email
santosh.kadam@astrazeneca.com
Details of Contact Person Public Query
Name
Dr Santosh Kadam
Designation
Director, SMM BioPharmaceuticals
Affiliation
AstraZeneca Pharma India Limited
Address
Block N1, 12th Floor, Manyata Embassy Business Park, Rachenahalli, Outer Ring Road
Bangalore KARNATAKA 560045 India
Phone
9535999494
Fax
Email
santosh.kadam@astrazeneca.com
Source of Monetary or Material Support
AstraZeneca AB
151 85 Södertälje, Sweden
Primary Sponsor
Name
AstraZeneca AB
Address
151 85 Södertälje, Sweden
Type of Sponsor
Pharmaceutical industry-Global
Details of Secondary Sponsor
Name
Address
AstraZeneca Pharma India Ltd
Block N1, 12th Floor, Manyata Embassy Business Park,
Rachenahalli, Outer Ring Road, Bangalore - 560045,
Karnataka, India
Countries of Recruitment
Argentina Brazil Bulgaria Denmark France Germany India Malaysia Netherlands Philippines Republic of Korea South Africa Spain Sweden Taiwan Thailand United Kingdom United States of America Viet Nam
Sites of Study
No of Sites = 7
Name of Principal
Investigator
Name of Site
Site Address
Phone/Fax/Email
Dr Srikanth Krishnamurthy
Hindusthan Hospital
Department of Pulmonology, 522/3, 523/3 Nava India Road, Udaiyampalayam, PIN- 641028 Coimbatore TAMIL NADU
9894257706
drsrikanthcbe@gmail.com
Dr Santhosh Kumar Puthukkudy Velayudhan
Institute of Chest Disease, Govt Medical College, Calicut
Department of Pulmonary Medicine, Kozhikode, PIN - 673008 Kozhikode KERALA
9837105779
drpvsksanam@gmail.com
Dr Piyush Arora
Jawaharlal Nehru Medical College
Department of Respiratory Diseases, Kala Bagh, PIN - 305001 Ajmer RAJASTHAN
9887088122
doctor.piyusharora@gmail.com
Dr Ravindra Reddy Etikala
Kamineni Hospitals Private Limited
Department of Respiratory Medicine, L.B Nagar, PIN- 500068, Hyderabad TELANGANA
9848023703
rvndrreddy@yahoo.com
Dr Jyothi Hattiholi
KLE Dr Prabhakar Kore Hospital & Medical Research Centre
Department of Pulmonology, Nehrunagar, PIN- 590010 Belgaum KARNATAKA
7022799910
pulmojyoti@gmail.com
Dr Jaydip Deb
Nil Ratan Sircar NRS Medical College and Hospital,
Department of Tuberculosis & Respiratory Chest Diseases, 138, AJC Bose Road, PIN -700014 Kolkata WEST BENGAL
9830439804
jaydip.deb@gmail.com
Dr Rohit Kumar
Vardhman Mahavir Medical College and Safdarjung Hospital
Department of Pulmonary Critical Care & Sleep Medicine, Ansari Nagar West, PIN 110029 New Delhi DELHI
Inhalation via Dry Powder Inhaler; Dose: 1.4 mg BID; Route: Inhalation via DPI; Frequency: BID at Day 1, Day 29 (+ – 3 days), Day 85 (+ – 3 days )
Comparator Agent
Placebo
Inhalation via Dry Powder Inhaler
Dose: 1.4 mg BID; Route: Inhalation via DPI; Frequency: BID at Day 1, Day 29 (+ – 3 days), Day 85 (+ – 3 days )
Inclusion Criteria
Age From
18.00 Year(s)
Age To
80.00 Year(s)
Gender
Both
Details
Age
1. Participant must be 18 to 80 years of age inclusive, at the time of signing the informed consent.
Type of Participant and Disease Characteristics
2. Participants treated with medium-high dose ICS (as per GINA 2022 ICS dose level table in Appendix F) in combination with LABA at a stable dose for at least 3 months prior to Visit 1 (the ICS can be contained within an ICS-LABA fixed dose combination product).
Treatment with additional asthma controller therapies (eg, LAMA, LTRA) at a stable dose ≥ 3 months prior to Visit 1 is allowed. Treatment with maintenance systemic corticosteroids (oral or injectable) is not allowed (see Section 5.2, Exclusion Criterion 12).
3. A documented history of ≥ 1 severe asthma exacerbation within 1 year prior to Visit 1. A severe asthma exacerbation is defined as a worsening of asthma that leads to any of the following:
Use of systemic corticosteroids for at least 3 consecutive days to treat symptoms of asthma worsening (a single depo-injectable dose of corticosteroids will be considered equivalent to a 3-day bolus/burst of systemic corticosteroids).
An emergency room visit (defined as evaluation and treatment for < 24 hours in an emergency department) due to asthma that required systemic corticosteroids (as per the above).
An inpatient hospitalization (defined as admission to an inpatient facility and/or evaluation and treatment in a healthcare facility for ≥ 24 hours) due to asthma.
Acceptable documentation of a severe asthma exacerbation in this protocol is:
Documented prescription of systemic corticosteroids for at least 3 days to treat asthma worsening (a single depo-injectable dose of corticosteroids will be considered equivalent to 3-day bolus/burst of systemic corticosteroids). In participants with an established self-management plan, documented filling of a prescription will be considered adequate.
Clinic visit or consultation (primary or specialized HCP) notes providing evidence of ≥1 exacerbation in the previous 12 months prior to enrolment.
Emergency room/hospital records that the participant attended an emergency room visit (defined as evaluation and treatment for < 24 hours in an emergency department) due to asthma that required systemic corticosteroids (as per the above).
Discharge summaries from hospital, emergency room or urgent care facility indicating that a participant was hospitalised (defined as admission to an inpatient facility and/or evaluation and treatment in a healthcare facility for 24 hours) due to asthma
4. Morning pre-BD FEV1 between ≥ 40% and ≤ 90% predicted at Visit 1 and Visit 3 (pre-randomisation).
5. Able to perform acceptable lung function testing for FEV1 according to ATS/ERS 2019 acceptability criteria.
6. Documented evidence of asthma as demonstrated by any of the following in the 10 years up to or including Visit 1:
Post-BD reversibility of FEV1 ≥ 12% and ≥ 200 mL, or
Average daily variability of PEF > 10% over a 2-week period, or
Variability of FEV1 > 12% and 200 mL between any 2 clinical visits, or
Positive bronchial challenge test (a positive test is defined as a fall in FEV1 from pre-challenge of ≥ 20% with standard doses of methacholine or histamine, or ≥ 15% with standardised hyperventilation, hypertonic saline, or mannitol challenge), or
Positive exercise challenge test (a positive test is defined as a fall in FEV1 of > 10% and > 200 mL from pre-challenge), or
A FeNO test with a value of ≥ 40 ppb despite confirmed ICS maintenance therapy.
If documentation is not available to support any of these diagnostic criteria, and if in the opinion of the investigator the clinical diagnosis of asthma is still considered likely, the investigation and confirmation of an average daily variability of PEF > 10% over a 2-week period can also be considered as confirmatory of the diagnosis of asthma if undertaken during the period of screening and run-in
7. An ACQ-6 score ≥ 1.5 at Visit 1 and at Visit 3 (pre-randomization).
8. Able and willing to comply with the requirements of the CSP including ability to read, write, be fluent in the translated language of all participants facing questionnaires used at the study site, and use electronic devices, eg, ePRO device and spirometer.
Weight
9. Body weight of ≥ 40 kg and body mass index of < 35 kg/m2.
Sex and Contraceptive/Barrier Requirements
10. Male and/or female
Contraceptive use by females should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. There are no restrictions on male participants or their female partners.
Females not of childbearing potential are defined as females who are either permanently sterilised (hysterectomy, bilateral oophorectomy, or bilateral salpingectomy), or who are postmenopausal. The following age-specific requirements apply:
Females < 50 years old would be considered postmenopausal if they have been amenorrhoeic for 12 months or more following cessation of exogenous hormonal treatment and follicle-stimulating hormone levels in the postmenopausal range.
Females ≥ 50 years old would be considered postmenopausal if they have been amenorrhoeic for 12 months or more following cessation of all exogenous hormonal treatment.
All FOCBP who are sexually active with a non-sterilised male partner must agree to use one highly effective method of birth control, as defined below, for a minimum of 3 months prior to Visit 1 and throughout entire duration of the study, and for 1 month after the last dose of IMP. Cessation of contraception after this point should be discussed with a responsible physician. A highly effective method of contraception is defined as one that can achieve a failure rate of < 1% per year when used consistently and correctly.
The following are not acceptable methods of contraception: Periodic abstinence (calendar, symptothermal, post-ovulation methods), declaration of abstinence for the duration of exposure to IMP, withdrawal (coitus interruptus), spermicides only, and lactational amenorrhoea. Female condom and male condom should not be used together.
All FOCBP must have a negative serum pregnancy test result at Visit 1
Highly effective birth control methods include: Total sexual abstinence is an acceptable method provided it is the usual lifestyle of the participant (defined as refraining from heterosexual intercourse during the entire period of risk associated with the IMP), a vasectomised partner, Implanon, bilateral tubal occlusion, intrauterine device/levonorgestrel intrauterine system, Depo-Provera injections, oral contraceptive, and Evra Patch, Xulane, or NuvaRing
Informed Consent
11. Capable of giving signed informed consent prior to any study-specific procedures as described in Appendix A which includes compliance with the requirements and restrictions listed in the ICF and in this CSP.
12. Provision of signed and dated written Optional Genetic Research Information informed consent prior to collection of samples for optional genetic research that supports the Genomic Initiative
Randomisation Inclusion Criteria
At the end of the Run-in period (Visit 3), participants must fulfil the following additional criteria in order to be randomised into the study and enter the Treatment period:
1. Pre-BD FEV1 between ≥ 40% and ≤ 90% predicted (pre-randomisation).
2. A pre-BD/pre-IMP dose FEV1 at Visit 3 that has not increased or decreased by 20% or more from the pre-BD FEV1 recorded at Visit 1 and at Visit 2.
3. An ACQ-6 score of ≥ 1.5 (pre-randomisation)
5. Minimum 80% compliance with daily eCOA assessments. Compliance is defined as completing the daily ePRO questions and PEF measurement (morning and evening) at least 80% of the time during the Run-in period and during the 14 days preceding Visit 3.
6. For female participants, a negative urine pregnancy test prior to administration of IMP
ExclusionCriteria
Details
Medical Conditions
1. A severe asthma exacerbation within 8 weeks of prior to randomisation. (For definition of severe exacerbation see Section 5.1, Inclusion Criterion 3).
2. History of herpes zoster reactivation eg, shingles
Participants with a significant COVID-19 illness within 6 months of enrolment:
Participants with a diagnosis of COVID-19 pneumonia based on radiological assessment.
Participants with a diagnosis of COVID-19 requiring hospitalisation and/or oxygen supplementation therapy.
4. Clinically important pulmonary disease other than asthma eg, active lung infection, COPD, bronchiectasis, pulmonary fibrosis, cystic fibrosis, hypoventilation syndrome associated with obesity, lung cancer, history or planned lung lobectomy, alpha-1 anti-trypsin deficiency, primary ciliary dyskinesia, Churg-Strauss syndrome, allergic bronchopulmonary aspergillosis and hyper-eosinophilic syndrome.
5. Any disorder, including, but not limited to, cardiovascular, gastrointestinal, hepatic, renal, neurological, musculoskeletal, infectious, endocrine, metabolic, haematological, psychiatric, or major physical impairment that is not stable in the opinion of the investigator and could:
affect the safety of the participant throughout the study,
influence the findings of the study or the interpretation, or
impede the participant s ability to complete the entire duration of study.
6. Any clinically significant cardiac or cerebrovascular disease:
Unstable angina, acute coronary syndrome (acute myocardial infarction, unstable angina), coronary intervention with percutaneous coronary intervention/coronary artery bypass surgery or stroke within 6 months of Visit 1.
Heart failure, New York Heart Association, Classes II to IV.
Systemic hypertension, except if well-controlled using 2 or fewer medications and stable for at least 6 months.
Untreated high degree atrioventricular block (second – third degree atrioventricular block)/significant sinus node dysfunction/pause or therapy requiring tachyarrhythmia. Participants with atrial fibrillation or flutter and optimally controlled ventricular rate at resting < 100 bpm might be included as judged by the investigator.
History or family history of long QT-syndrome or sudden cardiac death with age < 40 years old.
History of QT prolongation associated with other medications that required discontinuation of that medication.
Hypertrophic cardiomyopathy or clinically significant valvular heart disease.
Pulmonary arterial hypertension, either idiopathic or due to connective tissue or thromboembolic disease.
History of venous thromboembolism.
8. Participants who, as judged by the investigator, have evidence of active TB, either treated or untreated, or latent TB without completion of an appropriate course of treatment or appropriate ongoing prophylactic treatment. Evaluation will be according to the local standard of care as determined by local guidelines and may consist of history and physical examinations, chest X-ray, or TB test (eg, purified protein derivative or QuantiFERON test).
9. Participants with a recent history of, or who have a positive test for, infective hepatitis or unexplained jaundice, or participants who have been treated for hepatitis B, hepatitis C, or HIV. Any of the following would exclude the participant from the study:
Participants positive for hepatitis C antibody.
Participants positive for hepatitis B virus surface antigen.
Participants positive for hepatitis B virus core antibody.
Participants with history of infection or positivity of HIV.
Note: Participants with a history of hepatitis B vaccination without a history of hepatitis B are permitted. If vaccinated participants test positive for hepatitis B antibody, a confirmatory PCR test will be performed.
10. Current or prior history of alcohol or drug abuse (including marijuana), as judged by the investigator. Positive drug screening result that cannot be justified by participant s medical history and its relevant treatment (over-the-counter product or a valid prescription), or history of or current alcohol or drug abuse (including marijuana and marijuana-containing valid prescriptions), as judged by the investigator.
11. History of malignancy other than superficial basal cell carcinoma.
Prior/Concomitant Therapy
12. Treatment with systemic corticosteroid (short-term or maintenance) use within 4 weeks (oral) or 8 weeks (intramuscular) before Visit 1.
13. Any immunosuppressive therapy (including hydroxychloroquine, methotrexate, cyclosporine and tacrolimus) within 12 weeks prior to Visit 1.
14. Treatment with marketed biologics including benralizumab, mepolizumab, reslizumab, omalizumab, dupilumab and tezepelumab within 6 months of Visit 1 or 5 half-lives, whichever is longer.
15. Inhaled corticosteroid plus fast-acting β2 agonist as a reliever (eg, Symbicort, Fostair, or Airsupra Maintenance and Reliever Treatment) is not allowed 15 days prior to Visit 1, during Screening/Run-in and throughout the Treatment period and preferably 1 week after the last dose of IMP.
16. Live, attenuated, or mRNA vaccines within 4 weeks of Visit 1.
17. Immunoglobulin or blood products within 4 weeks of Visit 1.
18. Any immunotherapy within 6 months of Visit 1, except for stable maintenance dose allergen-specific immunotherapy started at least 4 weeks prior to Visit 1 and expected to continue through to the end of the Follow-up period.
Prior/Concurrent Clinical Study Experience
19. Concurrent enrolment in another clinical study.
20. Participant treated with any investigational drug within 4 months (or 5 half-lives, whichever is longer) prior to Visit 1.
21. Participants with a known hypersensitivity to AZD4604 or any of the excipients of the product.
Diagnostic Assessments
22. Abnormal findings identified on physical examination, ECG, or laboratory testing include, but are not limited to:
ALT or AST ≥ 1.5 × ULN.
TBL ≥ ULN (unless due to known Gilbert s disease).
Evidence of chronic liver disease.
Method of Generating Random Sequence
Stratified randomization
Method of Concealment
Centralized
Blinding/Masking
Participant and Investigator Blinded
Primary Outcome
Outcome
TimePoints
To evaluate the clinical efficacy of AZD4604 1.4 mg BID as compared to placebo in adult participants with moderate-to-severe uncontrolled asthma
Endpoint: Time to first CompEx event
Strategy of intercurrent eventsa: Intercurrent events are events occurring after treatment initiation that affect either the measurement or interpretation of the summary measure associated with the clinical question of interest.
Primary estimand: While on treatment – if an intercurrent event occurs before first CompEx event, the participant will be censored at the time of intercurrent event.
Secondary Outcome
Outcome
TimePoints
To evaluate the clinical efficacy of AZD4604 mg BID as
compared to placebo in adult participants with moderate-to-severe uncontrolled asthma
Change from baseline in FVC at Week 52Population: Analysis will include participants randomised to either placebo or AZD4604 BID arms
Endpoints -Change from baseline in
1.Pre-BD FEV1 at Week 4 and Week 12
2.CAAT at Week 4 and Week 12
3.ACQ-6 at Week 4 and Week 12
4.Average morning and average evening PEF at Week 4 and Week 12, and average over 12 WK Treatment period 5 Daily asthma symptom score at WK 4 and WK 12
Population level summary measure Average change from baseline
To evaluate the clinical efficacy of AZD4604 mg BID as
compared to placebo in adult participants with moderate-to-severe uncontrolled asthma
Strategy for intercurrent eventsa: Same as for primary objectives
Population: Analysis will include participants randomised to either placebo or AZD4604 BID arms
Endpoints
1 Time to first CompEx acute worsening event
2 CompEx event rate
3 CompEx acute worsening event rate
Population-level summary measure:
1 Hazard ratio, survival estimates by Kaplan-Meier estimator
To evaluate the clinical efficacy of AZD4604 mg BID as
compared to placebo in adult participants with moderate-to-severe uncontrolled asthma
Population-level summary measure:
1 Hazard ratio, survival estimates by Kaplan-Meier estimator
2 (a) Percentage of participants with at least 1 event
(b) Event rate normalised on study follow-up duration (12 weeks)
3 (a) Percentage of participants with at least 1 event
(b) Event rate normalised on study follow-up duration (12 weeks)
To evaluate the clinical efficacy of AZD4604 mg BID as
compared to placebo in adult participants with moderate-to-severe uncontrolled asthma
Strategy for intercurrent events:
1 While on treatment
2 Treatment policy
3 Treatment policy
To evaluate the effect of AZD4604 on airway inflammation as
measured by FeNO
Population: Analysis will include participants randomised to either placebo or AZD4604 BID arms
Endpoint: Change from baseline in FeNO at Week 4 and Week 12
Population-level summary measure: Average change from baseline to Week 4 and Week 12
Strategy for intercurrent events: Same as for the primary objectives
To evaluate the effect of AZD4604 BID on cough as compared to placebo in adult participants with moderate-to-severe uncontrolled asthma
Population: Analysis will include participants randomised to either placebo or
AZD4604 1.4 mg BID arms
Endpoints: Change from baseline in cough severity at Week 4, Week 12, and
over the Treatment period
Population-level summary measure: Average change from baseline
Strategy for intercurrent events: Same as for the primary objectives
To evaluate the PK of AZD4604 in all participants after 4 weeks and
12 weeks dosing
Population: All participants who had received at least 1 dose of AZD4604, and
who had at least one measurable PK sample after first dose.
Endpoint: AZD4604 plasma concentration pre- and post-dose at Week 4,
pre-dose at Week 12
Population-level summary measure: Summary statistics
Strategy for intercurrent events: While on treatment
To assess the safety and tolerability of AZD4604 BID in adult participants with moderate-to-severe uncontrolled asthma
Population: Analysis will include all participants randomised to either placebo
or AZD4604 1.4 mg BID arms.
Endpoint: Safety and tolerability evaluations using all AEs, vital sign measures,
clinical laboratory assessments, ECG
Population-level summary measure: Descriptive statistics including absolute
counts and frequencies
To assess the safety and tolerabilityof AZD4604 BID in adult participants with moderate to severe uncontrolled asthma uncontrolled asthma
Strategy for intercurrent eventsa:
Primary estimand: While on treatment – if an intercurrent event occurs, after the safety follow-up, any subsequent safety data will not be taken into consideration in the safety evaluation.
Supportive estimand: Treatment policy – if an intercurrent event occurs, participants remain in the study and any safety data until Week 12 plus safety follow-up will be taken into consideration in the safety evaluation.
Exploratory: To further evaluate the clinical efficacy of AZD4604 BID as compared to placebo in adult participants with moderate-to-severe uncontrolled asthma
Population: Analysis will include participants randomised to either placebo or AZD4604 BID arms
Endpoints: Change from baseline in:
1 Post-BD FEV1 at Week 12
2 Percent reversibility at Week 12
3 Forced expiratory flow 25 percentage -75 percentage at Week 4 and Week 12 Population-level summary measure: Average change from baseline
Strategy of intercurrent events: Same as for the primary objectives
Exploratory: To further evaluate the clinical efficacy of AZD4604 BID as compared to placebo in adult participants with moderate-to-severe uncontrolled asthma
Population: Analysis will include participants randomised to either placebo or AZD4604 BID arms
Endpoint: Time to first severe asthma exacerbation
Population-level summary measure: Hazard ratio, survival estimates by Kaplan-Meier estimator
Strategy for intercurrent events: While on treatment - if an intercurrent event occurs before first severe asthma exacerbation, the participant will be censored at the time of intercurrent event
To assess the association between AZD4604 response and participant
baseline characteristics including, FeNO, blood eosinophils level, and
ICS dose level
Population: Analysis will include participants randomised to either placebo or AZD4604 1.4 mg BID arms
Endpoint:
1 Time to first CompEx event
2 Change from baseline in pre-BD FEV1 at Week 4 and Week 12
3 Change from baseline in post-BD FEV1 at Week 12
4 Change from baseline in ACQ-6 and CAAT at Week 4 and Week 12
5 Change from baseline in FeNO at Week 4 and Week 12
To assess the association between AZD4604 response and participant
baseline characteristics including, FeNO, blood eosinophils level, and
ICS dose leve
Population-level summary measure:
1 Hazard ratio according to baseline characteristics
2 Average change from baseline pre-BD FEV1 according to baseline characteristics
3 Average change from baseline post-BD FEV1 according to baseline characteristics
4 Average change from baseline ACQ-6 and CAAT according to baseline characteristics
5 Average change from baseline FeNO according to baseline characteristics
Strategy of intercurrent events: Same as for the primary objectives
To assess participant self-reported impression of change in asthma symptoms after starting treatment
Population: Analysis will include participants randomised to either placebo or AZD4604 BID arms
Endpoint: Descriptive display of PGIC categories by treatment arm at Week 12
Population-level summary measure: Descriptive bar chart displaying percent participants in each category of PGIC in each treatment arm
To evaluate responder definition/analysis of change in CAAT scores
Population: Analysis will include participants randomised to either placebo or AZD4604 BID arms
Endpoint: Using PGIC as an anchor, define a responder on the CAAT total score by evaluating mean change on CAAT for each category of the PGIC response at Week 4 and Week 12
Population-level summary measure: Anchor-based responder analysis of the CAAT with a display of CDF plots
To assess the effects of AZD4604 as compared to placebo on
spirometry endpoints measured face-to-face and virtually in
participants with moderate-to-severe uncontrolled asthma
Population: Analysis will include participants randomised to either placebo or AZD4604 BID arms
Endpoints: Change from baseline in spirometry endpoints, including but not limited to PEF, FEV1, forced vital capacity, forced expiratory flow 25 percentage -75 percentage, inspiratory capacity, and reproducibility
Population-level summary measure: Average change from baseline
Strategy for intercurrent events: Treatment policy
To evaluate the impact of AZD4604 on exploratory biomarkers and
gene expression in blood, nasal lining fluid, nasal cells and urine
Population: Analysis will include participants randomised to either placebo or AZD4604 BID arms, who may be further stratified based on baseline
Endpoints: Change from baseline in biomarkers and gene expression associated with disease or the JAK-STAT pathway as well as LDL cholesterol, HDL cholesterol, and triglycerides at Week 12
To evaluate the impact of AZD4604 on exploratory biomarkers and gene expression in blood, nasal lining fluid, nasal cells and urine
To evaluate the impact of AZD4604 on exploratory biomarkers and gene expression in blood, nasal lining fluid, nasal cells and urine
Target Sample Size
Total Sample Size="320" Sample Size from India="30" Final Enrollment numbers achieved (Total)= "340" Final Enrollment numbers achieved (India)="22"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
This is a Phase 2a, multicentre, randomised,
placebo-controlled, double-blind, parallel-group study designed to evaluate the
efficacy, safety and PK of AZD4604 administered BID using the SD3FL dry-powder
inhaler at one dose level over a 12-week Treatment period in adult participants
with uncontrolled moderate-to-severe asthma. This study will include around 150
study sites globally.
Approximately 320 participants, with uncontrolled asthma despite receiving
treatment with medium or high dose ICS-LABA at screening and at Visit 3 (Asthma
Control Questionnaire-6 score ≥ 1.5) will be randomly assigned in a 1:1 ratio to 1 of the 2 treatment
arms (AZD4604 BID or placebo). To ensure balance between the treatment
arms, randomisation will be stratified based on participant’s ICS dose level at
Visit 1 (medium, high) and region.
AZD4604 1.4 mg and placebo will be administered BID using the SD3FL inhaler,
also known and marketed as Genuair® in the Europe and Pressair® in the United
States