- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02898662
AZD1419 Ph2a Study (INCONTRO)
A Phase 2 Placebo-Controlled, Randomized, Double Blind, Adaptive Dose Trial of the Safety and Efficacy of Inhaled AZD1419 in Adults With Eosinophilic, Moderate to Severe Asthma
Study Overview
Detailed Description
Ph2a study planned to be run in 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 study has a withdrawal design.The patients will receive 13 once weekly inhaled doses of the study drug (AZD1419 or placebo). Treatment is initiated with 6 doses of the study drug on top of their ICS/LABA controller medication. Prior to the 7th dose of the study drug the LABA is withdrawn. The following 3 doses are given when ICS is tapered down. Dose 7 is given on top of 100% of their ICS, dose 8 is given on top of 50% of the ICS dose, which is then tapered down to 25% the following week and withdrawn completely prior to dose 10 of the study drug. During the last 3 weeks of treatment (ie last 4 doses), 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, defined as any of the following criteria: a) An increase of ACQ-5 to 1.5 or more b) A reduction of 30% or more in morning peak expiratory flow (PEF) from baseline on 2 consecutive days c) At least six additional reliever inhalations of SABA in a 24-hour period relative to baseline on 2 consecutive days and d) An exacerbation requiring systemic corticosteroids
When the endpoint is met, patients will resume their regular ICS/LABA controller medication and will be followed for an additional 4 weeks, when they do an Early Discontinuation (ED) Visit and will thereafter leave the study. For patients not loosing their asthma control, the full Observational period is up to week 52, when they will do an End of Treatment Visit (EOT). Study procedures are the same on ED and EOT Visits.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
-
Hvidovre, Denmark, 2650
- Research Site
-
København NV, Denmark, 2400
- Research Site
-
Naestved, Denmark, 4700
- Research Site
-
Odense C, Denmark, 5000
- Research Site
-
-
-
-
-
Balassagyarmat, Hungary, 2660
- Research Site
-
Edelény, Hungary, 3780
- Research Site
-
Farkasgyepü, Hungary, 8582
- Research Site
-
Miskolc, Hungary, 3529
- Research Site
-
Törökbálint, Hungary, 2045
- Research Site
-
-
-
-
-
Gdańsk, Poland, 80-214
- Research Site
-
Lubin, Poland, 59-300
- Research Site
-
Łódź, Poland, 90-153
- Research Site
-
-
-
-
-
Linköping, Sweden, 587 58
- Research Site
-
Lund, Sweden, 221 85
- Research Site
-
Stockholm, Sweden, 141 86
- Research Site
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Placebo Comparator: Placebo
Matching placebo
|
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
|
Experimental: AZD1419
Dose adaption of AZD1419, 4 mg or 8 mg or 1 mg based on occurence of AE's
|
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
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Participants With Events for Time to Loss of Asthma Control (LOAC) up to Week 52 - Cox Regression Analysis
Time Frame: Baseline (Week 0) up to Week 52
|
LOAC was defined as any of the following:
|
Baseline (Week 0) up to Week 52
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Participants Experiencing LOAC up to Week 52 - Generalized Estimating Equation Analysis
Time Frame: Baseline (Week 0) up to Week 52
|
LOAC was defined as any of the following:
|
Baseline (Week 0) up to Week 52
|
Least Squares (LS) Mean ACQ-5 Score Over 52 Weeks
Time Frame: Baseline (Week 0) up to Week 52
|
In the ACQ-5 questionnaire, participants were asked to recall the status of their asthma during the previous week with regards to symptoms. The questionnaire included the items:
|
Baseline (Week 0) up to Week 52
|
LS Mean Asthma Daily Diary Score (Weekly Total) Over 52 Weeks
Time Frame: Baseline (Week 0) up to Week 52
|
Asthma symptoms during night-time and daytime were recorded by the participant each morning and evening in the Asthma Daily Diary.
Symptoms were recorded using a 4-point response scale, which ranged from 0 to 3, where 0 indicated no asthma symptoms.
Asthma symptom daytime score (recorded in the evening), night-time score (recorded in the morning), and total score were calculated separately.
The daily asthma symptom total score was calculated by taking the sum of the night-time and daytime asthma symptom scores recorded each day, ranging from 0 to 6.
A lower symptom score indicated a better outcome.
Estimates of the LS mean over 52 weeks were analyzed using a repeated measures analysis with treatment, baseline asthma daily diary weekly average, week and treatment-by-week with participant as random effects, and age and gender as covariates.
Baseline was the average of non-missing daily measures/scores over the last 5 days prior to and including the morning of randomization.
|
Baseline (Week 0) up to Week 52
|
Number of Participants With Events for Time to Moderate Or Severe Exacerbation up to Week 52
Time Frame: Baseline (Week 0) up to Week 52
|
Moderate exacerbation was defined as a temporary increase in maintenance therapy to prevent a severe event supported by sustained (≥ 2 day) worsening in at least 1 key control metric ie, asthma score, reliever medication use, night time awakening or morning PEF. Severe exacerbation was defined as a worsening in asthma symptoms and:
|
Baseline (Week 0) up to Week 52
|
Percentage of Participants Using Reliever Medication up to Week 52
Time Frame: Baseline (Week 0) up to Week 52
|
The use of SABAs was allowed as rescue medication (reliever bronchodilator) throughout the study.
Reliever medication use was captured in the Asthma Daily Diary twice daily (morning and evening), recorded as the number of inhaler puffs.
The number of inhalations (puffs) per day was calculated as: number of night inhaler puffs + number of day inhaler puffs.
Percentage of participants using reliever medication (SABA) up to Week 52 is presented.
|
Baseline (Week 0) up to Week 52
|
LS Mean Pre- and Post-Bronchodilator (BD) Forced Expiratory Volume in 1 Second (FEV1) Over 52 Weeks
Time Frame: Baseline (Week 0) up to Week 52
|
Lung function was assessed by pre- and post-BD FEV1 which was measured by spirometry.
To ensure quality control, all spirometry measurements were reviewed to ensure that they met American Thoracic Society / European Respiratory Society criteria for acceptability.
Estimates of the LS mean over 52 weeks were analyzed using a repeated measures analysis with treatment, baseline FEV1 (pre- or post-BD, as applicable), visit and treatment-by-visit with participant as random effects, and age and gender as covariates.
Baseline was the last non-missing measurement recorded prior to randomization.
|
Baseline (Week 0) up to Week 52
|
LS Mean Total PEF (Weekly) Over 52 Weeks
Time Frame: Baseline (Week 0) up to Week 52
|
Morning and evening PEF measurements were recorded by the participant on a daily basis and then averaged over the week.
The weekly average total PEF was calculated by taking the sum of the average of the weekly morning mean and weekly evening mean.
Estimates of the LS mean over 52 weeks were analyzed using a repeated measures analysis with treatment, baseline PEF, week and treatment-by-week with participant as random effects, and age and gender as covariates.
Baseline was the average of non-missing daily measures/scores over the last 5 days prior to and including the morning of randomization.
|
Baseline (Week 0) up to Week 52
|
LS Mean Fractional Exhaled Nitric Oxide (FeNO) (Weekly) Over 52 Weeks
Time Frame: Baseline (Week 0) up to Week 52
|
FeNO measurements were taken at home by participants every second day.
The weekly average FeNO was based on the average of measurements taken at home for a specific week.
Estimates of the LS mean over 52 weeks were analyzed using a repeated measures analysis with treatment, baseline FeNO, week and treatment-by-week with participant as random effects, and age and gender as covariates.
Baseline was the average of non-missing daily measures/scores over the last 5 days prior to and including the morning of randomization.
|
Baseline (Week 0) up to Week 52
|
Collaborators and Investigators
Sponsor
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- D2500C00003
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Asthma
-
Vanderbilt University Medical CenterNot yet recruitingAsthma in Children | Asthma Attack | Asthma Acute | Acute Asthma Exacerbation | Asthma; StatusUnited States
-
University of California, San FranciscoCompletedAsthma in Children | Asthma Attack | Asthma Acute | Asthma ChronicUnited States
-
SingHealth PolyclinicsNot yet recruitingAsthma | Asthma in Children | Asthma Attack | Asthma Acute | Asthma Chronic
-
Johann Wolfgang Goethe University HospitalCompleted
-
Universita di VeronaCompleted
-
Parc de Salut MarActive, not recruitingAsthma in Children | Persistent Asthma | Asthma ExacerbationSpain
-
Forest LaboratoriesCompleted
-
Brunel UniversityKarolinska InstitutetUnknown
-
Value Outcomes Ltd.AstraZenecaCompletedAsthma, Bronchial | Bronchial Asthma | Asthma Chronic | Asthma; EosinophilicCzechia