AZD1419 Ph2a Study

NCT02898662 | Completed Phase 2 Results DMC

• 1 other identifier: D2500C00003
• Study Type: interventional
• Target: 81
• Locations: 4 countries
• Sites: 15

Brief Summary

Ph2a study planned to be run at approximately 16-18 sites in 4 EU countries (Denmark, Hungary, Poland and Sweden) enrolling approximately 170 patients to ensure 70 randomized patients with eosinophilic, moderate to severe asthma. The patients will receive 13 once weekly inhaled doses of the study drug. Treatment is initiated on top of their ICS/LABA controller medication, which is then tapered down and withdrawn during a period of 3 weeks and during the last 3 weeks of treatment the study drug is given as monotherapy. SABA is used as reliever medication during the whole study period. Primary endpoint is Loss of asthma control. When the endpoint is met, patients will resume their ICS/LABA, will be followed for an additional 4 weeks and will thereafter discontinue the study.

Conditions

Asthma

Keywords

inhaled; TLR9 agonist; withdrawal design; loss of control

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Events for Time to Loss of Asthma Control (LOAC) up to Week 52 - Cox Regression Analysis

  LOAC was defined as any of the following: * Increase of asthma control questionnaire-5 (ACQ-5) to ≥ 1.5. * ≥ 30% reduction in morning peak expiratory flow (PEF) from baseline on 2 consecutive days. * ≥ 6 additional reliever inhalations of short-acting β agonist (SABA) in a 24-hour period relative to baseline on 2 consecutive days. * Exacerbation requiring systemic corticosteroids as decided by Investigator. Time to LOAC was calculated as start date of first LOAC - date of randomization + 1. Start date of LOAC was latest date that 1 of the 4 criteria were satisfied immediately prior to the exacerbation start date, provided no more than 7 days between LOAC and exacerbation start date. Time to LOAC was displayed using a Kaplan-Meier plot and the outcome measure is presented as number of participants with events. Cox regression analysis was used to compare treatments.

  Baseline (Week 0) up to Week 52

Secondary Outcomes (8)

• Number of Participants Experiencing LOAC up to Week 52 - Generalized Estimating Equation Analysis

  Baseline (Week 0) up to Week 52

• Least Squares (LS) Mean ACQ-5 Score Over 52 Weeks

  Baseline (Week 0) up to Week 52

• LS Mean Asthma Daily Diary Score (Weekly Total) Over 52 Weeks

  Baseline (Week 0) up to Week 52

• Number of Participants With Events for Time to Moderate Or Severe Exacerbation up to Week 52

  Baseline (Week 0) up to Week 52

• Percentage of Participants Using Reliever Medication up to Week 52

  Baseline (Week 0) up to Week 52

Study Arms (2)

AZD1419

EXPERIMENTAL

Dose adaption of AZD1419, 4 mg or 8 mg or 1 mg based on occurence of AE's

Drug: AZD1419

Placebo

PLACEBO COMPARATOR

Matching placebo

Drug: Placebo

Interventions

AZD1419 DRUG

Inhaled AZD1419 administered at the clinic as once weekly inhalations with the I-neb® device. Start dose is 4 mg and dose adaptation is applied (downtitration to 1mg or uptitration to 8 mg or remain on 4 mg) based on appearance of flu like adverse events

AZD1419

Placebo DRUG

Inhaled Placebo administered at the clinic as once weekly inhalations with the I-neb® device. Start dose is Placebo 4 mg and dose adaptation is applied (downtitration to 1mg or uptitration to 8 mg or remain on 4 mg) based on appearance of flu like adverse events

Placebo

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female patients 18 years and above
• Physician-diagnosed asthma requiring treatment with ICS and a long-acting beta agonist (LABA). Patients must have taken ICS plus LABA controller medication for at least 3 months prior to screening
• Pre-bronchodilator forced expiratory volume in 1 second (FEV1) ≥50% predicted
• Female patients must be 1 year post-menopausal, surgically sterile, or using an acceptable method of contraception
• Male patients must be surgically sterile or using an acceptable method of contraception (defined as barrier methods in conjunction with spermicides) from the first dose of the IMP and until 1 month after the last dose of the IMP to prevent pregnancy in a partner
• Blood eosinophil levels ≥ 250 cells/μL at screening OR a history of blood eosinophil levels ≥ 250 cells/μL at any time in the preceding 2 years AND blood eosinophil levels ≥ 150 cells /μL at screening. The eosinophilia must be believed to be due to asthma and not have other known causes, e.g. helminth infection
• ACQ-5 score ≤1.5 at screening
• ACQ-5 score ≤0.75 at randomization
• Documentation of any of the following within 5 years prior to Visit 1:
• Proof of post-bronchodilator reversibility in FEV1 of ≥12% and ≥200 mL
• Proof of a positive response to a methacholine or histamine challenge (a decrease in FEV1 by 20% \[PC20\] at ≤8 mg/mL)
• Proof of positive response to mannitol challenge (a decrease in FEV1 by 15% \[PD15\] at ≤635 mg or a \>10% decrease in FEV1 between consecutive doses)
• Proof of diurnal variability in PEF \>20% over the course of 24 hours in at least 4 out of 7 consecutive days If historical documentation is not available, proof of reversibility or a positive response to a methacholine, histamine or mannitol challenge or diurnal variation must be demonstrated according to above and documented during Visit 1

You may not qualify if:

• Clinically significant lung disease other than asthma (eg, chronic obstructive pulmonary disease, cystic fibrosis, allergic bronchopulmonary aspergillosis, active tuberculosis).
• History of autoimmune disease including but not limited to Wegener's granulomatosis, system lupus erythematosus, rheumatoid arthritis, Sjögren's syndrome, multiple sclerosis, autoimmune thrombocytopenia, primary biliary cirrhosis or any other autoimmune disease considered clinically relevant by the investigator
• Ongoing allergen immunotherapy or plans to begin such therapy during the study period
• DLco ≤ 60% of the lower limit of normal
• Breast feeding, pregnancy or intention to become pregnant during the course of the study
• Changes in chest X-ray suggesting clinically significant parenchymal disease other than asthma

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (15)

Research Site

Hvidovre, 2650, Denmark

Location

Research Site

København NV, 2400, Denmark

Location

Research Site

Næstved, 4700, Denmark

Location

Research Site

Odense C, 5000, Denmark

Location

Research Site

Balassagyarmat, 2660, Hungary

Location

Research Site

Edelény, 3780, Hungary

Location

Research Site

Farkasgyepü, 8582, Hungary

Location

Research Site

Miskolc, 3529, Hungary

Location

Research Site

Törökbálint, 2045, Hungary

Location

Research Site

Gdansk, 80-214, Poland

Location

Research Site

Lodz, 90-153, Poland

Location

Research Site

Lubin, 59-300, Poland

Location

Research Site

Linköping, 587 58, Sweden

Location

Research Site

Lund, 221 85, Sweden

Location

Research Site

Stockholm, 141 86, Sweden

Location

Related Links

• Protocol
• Statistical Analysis Plan (SAP)

MeSH Terms

Conditions

Asthma; Respiratory Aspiration

Interventions

AZD1419

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Respiration Disorders; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Global Clinical Lead
• Organization: AstraZeneca

ClinicalTrialTransparency@astrazeneca.com

+1 302 885 1180

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: August 16, 2016
• First Posted: September 13, 2016
• Study Start: October 12, 2016
• Primary Completion: September 25, 2018
• Study Completion: September 25, 2018
• Last Updated: November 6, 2019
• Results First Posted: October 21, 2019

Record last verified: 2019-10

Locations

SE (3); HU (5); PL (3); DK (4)