Efficacy and Safety of Inhaled AZD1402 Administered for Four Weeks in Adults With Asthma on Medium-to-High Dose Inhaled Corticosteroids

NCT04643158 | Terminated Phase 2 Results DMC

• 2 other identifiers: D2912C000032020-002828-37
• Study Type: interventional
• Target: 72
• Locations: 10 countries
• Sites: 40

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.

Conditions

Asthma

Keywords

AZD1402; placebo; Anticalin® protein; dry powder inhaler; inhaled corticosteroids; efficacy; safety

Outcome Measures

Primary Outcomes (5)

• Part 1: Number of Participants With Adverse Events (AEs)

  The safety and tolerability of AZD1402 compared to placebo at different dose levels in adults with asthma controlled on medium dose ICS-LABA was evaluated.

  From Screening (Week -6) until Follow-up (Day 56)

• Part 2: Change From Baseline in Pre-bronchodilator FEV1

  The efficacy of inhaled AZD1402 compared to placebo in adults with asthma uncontrolled on medium-to-high dose ICS-LABA was investigated.

  Baseline and Week 4

• Part 1: Change From Baseline in High-sensitivity C-reactive Protein (hsCRP)

  The safety and tolerability of AZD1402 compared to placebo at different dose levels in adults with asthma controlled on medium dose ICS-LABA was evaluated.

  Baseline, Day 12, Day 16, and Day 56

• Part 1: Change From Baseline in FEV1 In-clinic Spirometry

  The safety and tolerability of AZD1402 compared to placebo at different dose levels in adults with asthma controlled on medium dose ICS-LABA was evaluated.

  Baseline, Day 1, Day 7, Day 14, Day 28, and Day 56

• Part 1: Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) (In-clinic)

  The safety and tolerability of AZD1402 compared to placebo at different dose levels in adults with asthma controlled on medium dose ICS-LABA was evaluated.

  Baseline, Day 1, Day 7, Day 14, Day 28, and Day 56

Secondary Outcomes (21)

• Part 1 and Part 2: Antidrug Antibodies (ADA) Titers

  Day 1 until Day 56

• Part 1 and Part 2: Maximum Observed Serum (Peak) Drug Concentration (Cmax)

  Day 1 until Day 56

• Part 1 and Part 2: Half-life Associated With Terminal Slope (λz) of a Semi-logarithmic Concentration-time Curve (t1/2λz)

  Day 1 until Day 56

• Part 1 and Part 2: Area Under Plasma Concentration-time Curve in the Dosing Interval τ (AUCτ)

  Day 1 until Day 56

• Part 1 and Part 2: Area Under the Plasma Concentration-curve From Zero to the Last Quantifiable Concentration (AUClast)

  Day 1 until Day 56

Study Arms (4)

Part 1 and Part 2: AZD1402 Dose 1

EXPERIMENTAL

Randomised participants will receive oral inhalation of AZD1402 Dose 1 via DPI.

Drug: AZD1402; Drug: Short acting beta agonist (SABA) (rescue medication); Drug: Run-in medications (ICS-LABA combination)

Part 1 and Part 2: AZD1402 Dose 2

EXPERIMENTAL

Randomised participants will receive oral inhalation of AZD1402 Dose 2 via DPI.

Drug: AZD1402; Drug: Short acting beta agonist (SABA) (rescue medication); Drug: Run-in medications (ICS-LABA combination)

Part 1: AZD1402 Dose 3

EXPERIMENTAL

Randomised participants will receive oral inhalation of AZD1402 Dose 3 via DPI.

Drug: AZD1402; Drug: Short acting beta agonist (SABA) (rescue medication); Drug: Run-in medications (ICS-LABA combination)

Part 1 and Part 2: Placebo

PLACEBO COMPARATOR

Randomised participants will receive oral inhalation of matching placebo via DPI.

Drug: Placebo; Drug: Short acting beta agonist (SABA) (rescue medication); Drug: Run-in medications (ICS-LABA combination)

Interventions

AZD1402 DRUG

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

Part 1 and Part 2: AZD1402 Dose 1; Part 1 and Part 2: AZD1402 Dose 2; Part 1: AZD1402 Dose 3

Placebo DRUG

Randomised participants will receive oral inhalation of matching placebo via DPI.

Part 1 and Part 2: Placebo

Short acting beta agonist (SABA) (rescue medication) DRUG

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)

Part 1 and Part 2: AZD1402 Dose 1; Part 1 and Part 2: AZD1402 Dose 2; Part 1 and Part 2: Placebo; Part 1: AZD1402 Dose 3

Run-in medications (ICS-LABA combination) DRUG

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.

Part 1 and Part 2: AZD1402 Dose 1; Part 1 and Part 2: AZD1402 Dose 2; Part 1 and Part 2: Placebo; Part 1: AZD1402 Dose 3

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (40)

Research Site

Herston, 4006, Australia

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Melbourne, IC 3004, Australia

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Nedlands, 6009, Australia

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Windsor, Ontario, N8X 1T3, Canada

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Québec, Quebec, G1G 4A2, Canada

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Berlin, 10119, Germany

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Berlin, 10625, Germany

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Berlin, 10717, Germany

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Berlin, 14050, Germany

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Bonn, 53119, Germany

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Frankfurt, 60596, Germany

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Hamburg, 20354, Germany

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Hanover, D-30173, Germany

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Lübeck, 23552, Germany

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Csorna, 9300, Hungary

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Szombathely, 9700, Hungary

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Bialystok, 15-044, Poland

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Krakow, 30-033, Poland

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Krakow, 31-501, Poland

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Lodz, 90-302, Poland

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Lubin, 59-300, Poland

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Sopot, 81-741, Poland

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Wroclaw, 53-301, Poland

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Cheongiu, 28644, South Korea

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Incheon, 21431, South Korea

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Namdong-gu, 21565, South Korea

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Seoul, 02841, South Korea

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Seoul, 03312, South Korea

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Seoul, 06591, South Korea

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Seoul, 08308, South Korea

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Suwon, 16499, South Korea

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Barcelona, 08916, Spain

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Santiago de Compostela, 15706, Spain

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Villarreal, 12540, Spain

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Kaohsiung City, 807, Taiwan

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Kiev, 02000, Ukraine

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High Wycombe, HP11 2QW, United Kingdom

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Liverpool, L7 8XP, United Kingdom

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London, SE1 9RT, United Kingdom

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London, W1G 8HU, United Kingdom

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Related Links

• CSR Synopsis
• CSP
• SAP

MeSH Terms

Conditions

Asthma

Interventions

3-(2-(4-azidobenzamidino)ethyl)-5-hydroxyindole

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Limitations and Caveats

Terminated (The decision was based on lung findings from a non-clinical 13-week Good Laboratory Practice (GLP) toxicology study, which are not a concern for the active clinical studies but do not support long-term use and progression to later-stage development).

Results Point of Contact

• Title: Global Clinical Lead
• Organization: AstraZeneca

information.center@astrazeneca.com

1-877-240-9479

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 23, 2020
• First Posted: November 24, 2020
• Study Start: March 12, 2021
• Primary Completion: July 20, 2023
• Study Completion: July 20, 2023
• Last Updated: August 28, 2025
• Results First Posted: August 28, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: 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.
• Access Criteria: 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.

Locations

HU (2); CA (2); KR (8); ES (3); TW (1); PL (7); AU (3); DE (9); UA (1); GB (4)