A Study to Assess the Efficacy and Safety of Multiple Dose Levels of AZD7594 Administered Once Daily by Inhalation in Asthmatic Subjects

NCT ID: NCT03622112

Last Updated: 2020-11-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 808 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-01-02
• Study Completion Date: 2019-09-30

Brief Summary

This study will assess the efficacy and safety of multiple dose levels of AZD7594 administered once daily (QD) by inhalation in a 12-week treatment period on asthma subjects. The activity will be assessed by comparing AZD7594 to placebo. The comparison between active comparator (FF) and placebo will be used for bench marking. The efficacy is assessed by the evaluation of change in trough forced expiratory volume in 1 second (FEV1). The aim is to develop AZD7594 as a once daily inhaled non-steroidal selective GR modulator (SGRM), which may ultimately lead to better disease control of both chronic obstructive pulmonary disease (COPD) and asthma through improved efficacy and compliance. The overall rationale for developing a once daily AZD7594 in a dry powder inhaler (DPI) is to provide a safe and effective future treatment option for both asthma and COPD subjects.

Detailed Description

This is a randomised, placebo-controlled, double-blind multi center (8 countries: Europe, United States [US], South Africa, and Japan) study conducted on 714 subjects (102 subject per arm) with asthma symptomatic on low dose inhaled corticosteroids (ICS). The study consists of 3 periods:

• Run-in period (21-28 days; visits 1 to 3)
• Treatment period (12-week; Visits 4 to 7)
• Follow-up (1-week; visit 8).

The Run-in period consist of 3 visits: Screening visit (1), reversibility visit (2) and randomization visit (3). All subjects will sign an informed consent form (ICF) prior to participating in any study-specific procedures. Subjects found to be eligible at Visit 1 (Screening Visit) will discontinue all asthma medications and switch to low dose budesonide (200 μg twice a day [BID] in Europe and 180 μg BID in US) and rescue medication will be taken as needed. Subjects on long-acting beta agonist (LABA), fixed dose combination ICS/LABA treatment or a long-acting muscarinic antagonist (LAMA) will return for Visit 2 between 2 to 7 days after Visit 1 to have a sufficient wash-out time of their asthma medications. If reversibility criteria are met at Visit 2, subjects will proceed to Visit 3 (Randomization will occur within 21 to 28 days of Visit 1). At Visit 3, subjects who remain symptomatic while on low dose budesonide will be randomized in an overall ratio of 1:1:1:1:1:1:1 to one of 7 possible treatments and will receive inhalation powder via oral route:

• AZD7594 DPI 55μg [nominal strength]/50 μg [delivered dose] (QD)
• AZD7594 DPI 99 μg/90 μg QD
• AZD7594 DPI 198 μg/180 μg QD
• AZD7594 DPI 396 μg/360 μg QD
• AZD7594 DPI 792 μg/720 μg QD
• Placebo for AZD7594 QD
• FF 100 μg QD (open-label) The follow-up will be done by telephone contact within 7 to 10 days after Visit 7 or last investigational product (IP) intake.

The total duration of the study will be between 113 to 135 days for each individual subject and is planned to run approximately 12 months (it should not exceed 18 months).

Conditions

Asthma

Keywords

Inhaled non-steroidal glucocorticoid receptor modulator; Asthma; Inhaled corticosteroids.; Glucocorticoid receptor (GA) agonists.; Chronic obstructive pulmonary disease.; Short-acting B2 agonist.; Fluticasone furoate.

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

AZD7594 Dose 1

The randomized subjects will receive AZD7594 55 μg/50 μg (nominal/delivered dose), oral inhalation via dry powder inhaler (DPI) once daily.

Group Type: EXPERIMENTAL

AZD7594 DPI 55μg/50μg.

Intervention Type: DRUG

A non-steroidal and selective modulator of the GR.

AZD7594 Dose 2

The randomized subjects will receive AZD7594 99 µg/90 µg, oral inhalation via DPI once daily.

Group Type: EXPERIMENTAL

AZD7594 DPI 99 µg/90 µg

Intervention Type: DRUG

A non-steroidal and selective modulator of the GR.

AZD7594 Dose 3

The randomized subjects will receive treatment with AZD7594 198 µg/180 µg, oral inhalation via DPI once daily.

Group Type: EXPERIMENTAL

AZD7594 DPI 198 µg/180 µg

Intervention Type: DRUG

A non-steroidal and selective modulator of the GR.

AZD7594 Dose 4

The randomized subjects will receive treatment with AZD7594 396 µg/360 µg, oral inhalation via DPI once daily.

Group Type: EXPERIMENTAL

AZD7594 DPI 396 µg/360 µg once daily.

Intervention Type: DRUG

A non-steroidal and selective modulator of the GR.

AZD7594 Dose 5

The randomized subjects will receive treatment with AZD7594 792 µg/720 µg, oral inhalation via DPI once daily.

Group Type: EXPERIMENTAL

AZD7594 DPI 792 µg/720 µg

Intervention Type: DRUG

A non-steroidal and selective modulator of the GR.

Placebo

The randomized subjects will receive AZD7594 matching placebo oral inhalation via DPI once daily.

Group Type: PLACEBO_COMPARATOR

Placebo for AZD7594 once daily.

Intervention Type: DRUG

Placebo for AZD7594

Fluticasone Furoate

The randomized subjects will receive treatment with fluticasone furoate (FF) oral inhalation via DPI, 100 µg per nominal dose, once daily (open-label).

Group Type: ACTIVE_COMPARATOR

FF 100 µg once daily (open-label)

Intervention Type: DRUG

Fluticasone furoate

Interventions

AZD7594 DPI 55μg/50μg.

A non-steroidal and selective modulator of the GR.

Intervention Type: DRUG

AZD7594 DPI 99 µg/90 µg

A non-steroidal and selective modulator of the GR.

Intervention Type: DRUG

AZD7594 DPI 198 µg/180 µg

A non-steroidal and selective modulator of the GR.

Intervention Type: DRUG

AZD7594 DPI 396 µg/360 µg once daily.

A non-steroidal and selective modulator of the GR.

Intervention Type: DRUG

AZD7594 DPI 792 µg/720 µg

A non-steroidal and selective modulator of the GR.

Intervention Type: DRUG

Placebo for AZD7594 once daily.

Placebo for AZD7594

Intervention Type: DRUG

FF 100 µg once daily (open-label)

Fluticasone furoate

Intervention Type: DRUG

Eligibility Criteria

Exclusion Criteria

1. Known or suspected hypersensitivity to any of the IPs, including budesonide, or excipients, including lactose

2. Systemic steroid use within the 6 weeks before Visit 1

3. Concomitant chronic respiratory disease (including current sleep apnea)

4. History or clinical suspicion of any clinically relevant or active disease or disorder which, in the opinion of the Investigator, may either put the subject at risk because of participation in the study, or influence the results or the subject's ability to participate in the study, or any other safety concerns in the opinion of the Investigator

5. Use of prohibited medications that cannot be stopped during the entire period of the study (starting Visit 1).

6. Subjects with <80% eDiary compliance during Run in Period at Visit 3

7. ACQ-5 of ≥3 at Visit 1, Visit 2, or Visit 3

8. Daily rescue use of SABA ≥12 puffs for ≥3 consecutive days at any time during Run-in Period, before randomisation

9. Any clinically important abnormalities in rhythm, conduction or morphology of the digital ECG at rest and any abnormalities in the digital ECG (at Visit 1 or Visit 3) that, as considered by the Investigator, may interfere with the interpretation of QT interval corrected (QTc) interval changes

10. Prolonged QT interval corrected using Fridericia's formula (QTcF) ≥450 msec based on ECG at Visit 1 or Visit 3; or family history of long QT syndrome

11. PR (PQ) interval prolongation (>240 msec), intermittent second or third degree atrial-ventricular (AV) block or AV dissociation at Visit 1 or Visit 3

12. Subjects with implantable cardiac defibrillator and subjects with sustained symptomatic ventricular and/or atrial tachyarrhythmia

13. Subjects with unstable angina pectoris or stable angina pectoris classified higher than Canadian Cardiovascular Society Class II, or a myocardial infarction or stroke within 6 months before Visit 1

14. History of hospitalisation within 12 months before Visit 1 caused by heart failure or a diagnosis of heart failure higher than New York Heart Association Class II

15. Subjects who are positive for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody or human immunodeficiency virus (HIV) at Visit 1

16. Donation of blood (≥ 450 mL) within 3 months or donation of plasma within 14 days before Visit 1

17. Suspected poor capability to follow instructions of the study, as judged by the Investigator

18. Previous participation or prior screen failure in the current study, or participation in any other research study within 1 month prior to Visit 1

19. Subject under treatment with biologicals such as monoclonal antibodies or chimeric biomolecules including omalizumab, mepolizumab, and reslizumab within 6 months or 5 half-lives before Visit 1, whichever is longer

20. Subject treated with any investigational drug within 30 days (or 5 half-lives, whichever is longer) prior to Visit 1

21. Positive drug screening result that cannot be justified by subject'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

22. Planned in-patient surgery, major dental procedure or hospitalisation during the study

23. Pregnant woman or lactating woman

24. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff, contract research organisation staff and/or staff at the study centre)

25. Suspicion of Gilbert's syndrome

26. Vulnerable persons (eg, persons kept in detention)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Parexel

INDUSTRY

Sponsor Role: collaborator

AstraZeneca

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Kai Michael Beeh, Dr med

Role: PRINCIPAL_INVESTIGATOR

Insaf - Institut für Atemwegsforschung GmbH, D65187, Germany.

Locations

Research Site

Sheffield, Alabama, United States

Research Site

Phoenix, Arizona, United States

Research Site

Fullerton, California, United States

Research Site

Gold River, California, United States

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New Haven, Connecticut, United States

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Celebration, Florida, United States

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Miami, Florida, United States

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Port Orange, Florida, United States

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Winter Park, Florida, United States

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North Dartmouth, Massachusetts, United States

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Farmington Hills, Michigan, United States

Research Site

Charlotte, North Carolina, United States

Research Site

Gastonia, North Carolina, United States

Research Site

Raleigh, North Carolina, United States

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Cincinnati, Ohio, United States

Research Site

Dublin, Ohio, United States

Research Site

Medford, Oregon, United States

Research Site

Portland, Oregon, United States

Research Site

Spartanburg, South Carolina, United States

Research Site

Boerne, Texas, United States

Research Site

San Antonio, Texas, United States

Research Site

Gabrovo, , Bulgaria

Research Site

Kozloduy, , Bulgaria

Research Site

Plovdiv, , Bulgaria

Research Site

Rousse, , Bulgaria

Research Site

Sofia, , Bulgaria

Research Site

Sofia, , Bulgaria

Research Site

Stara Zagora, , Bulgaria

Research Site

Vidin, , Bulgaria

Research Site

Berlin, , Germany

Research Site

Berlin, , Germany

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Berlin, , Germany

Research Site

Berlin, , Germany

Research Site

Berlin, , Germany

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Dortmund, , Germany

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Großhansdorf, , Germany

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Hamburg, , Germany

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Hanover, , Germany

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Lübeck, , Germany

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Marburg, , Germany

Research Site

Wiesbaden, , Germany

Research Site

Balassagyarmat, , Hungary

Research Site

Budapest, , Hungary

Research Site

Gödöllő, , Hungary

Research Site

Komló, , Hungary

Research Site

Miskolc, , Hungary

Research Site

Nyíregyháza, , Hungary

Research Site

Pécs, , Hungary

Research Site

Százhalombatta, , Hungary

Research Site

Szigetszentmiklós, , Hungary

Research Site

Szombathely, , Hungary

Research Site

Chūōku, , Japan

Research Site

Fukuoka, , Japan

Research Site

Fukuoka, , Japan

Research Site

Himeji, , Japan

Research Site

Kagoshima, , Japan

Research Site

Kishiwada-shi, , Japan

Research Site

Naka-gun, , Japan

Research Site

Osaka, , Japan

Research Site

Sakaide-shi, , Japan

Research Site

Shinjuku-ku, , Japan

Research Site

Tokyo, , Japan

Research Site

Yanagawa-shi, , Japan

Research Site

Yokohama, , Japan

Research Site

Bialystok, , Poland

Research Site

Częstochowa, , Poland

Research Site

Kielce, , Poland

Research Site

Krakow, , Poland

Research Site

Ksawerów, , Poland

Research Site

Ostrowiec Świętokrzyski, , Poland

Research Site

Proszowice, , Poland

Research Site

Skarżysko-Kamienna, , Poland

Research Site

Skierniewice, , Poland

Research Site

Sopot, , Poland

Research Site

Tarnów, , Poland

Research Site

Bellville, , South Africa

Research Site

Johannesburg, , South Africa

Research Site

Mowbray, , South Africa

Research Site

Port Elizabeth, , South Africa

Research Site

Cherkasy, , Ukraine

Research Site

Ivano-Frankivsk, , Ukraine

Research Site

Kharkiv Region, , Ukraine

Research Site

Kharkiv Region, , Ukraine

Research Site

Kharkiv Region, , Ukraine

Research Site

Kyiv, , Ukraine

Research Site

Kyiv, , Ukraine

Research Site

Kyiv, , Ukraine

Research Site

Kyiv, , Ukraine

Research Site

Lutsk, , Ukraine

Research Site

Odesa, , Ukraine

Research Site

Poltava, , Ukraine

Research Site

Sumy, , Ukraine

Research Site

Vinnytsia, , Ukraine

Research Site

Zaporizhzhia, , Ukraine

Countries

United States; Bulgaria; Germany; Hungary; Japan; Poland; South Africa; Ukraine

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

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The SAP redacted.

Other Identifiers

D3741C00007

Identifier Type: -

Identifier Source: org_study_id