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History of Changes for Study: NCT02898662
AZD1419 Ph2a Study (INCONTRO)
Latest version (submitted October 9, 2018) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 September 8, 2016 Nothing (earliest Version on record)
2 September 13, 2016 Conditions, Study Status and Study Identification
3 October 20, 2016
Recruitment Status
, Study Status, Contacts/Locations and Oversight
4 November 25, 2016 Study Status and Contacts/Locations
5 January 5, 2017 Study Status
6 February 3, 2017 Study Status
7 March 10, 2017 Study Status and Contacts/Locations
8 April 11, 2017 Study Status and Contacts/Locations
9 May 16, 2017 Contacts/Locations and Study Status
10 June 20, 2017 Study Status
11 July 20, 2017 Study Status
12 August 10, 2017 Study Status
13 September 21, 2017
Recruitment Status
, Study Status, Contacts/Locations and Study Design
14 December 20, 2017 Study Status and Study Design
15 March 28, 2018 Study Status
16 July 5, 2018 Study Status
17 October 9, 2018
Recruitment Status
and Study Status
Comparison Format:

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Changes (Merged) for Study: NCT02898662
July 5, 2018 (v16) -- October 9, 2018 (v17)

Changes in: Study Status

Study Identification
Unique Protocol ID: D2500C00003
Brief Title: AZD1419 Ph2a Study (INCONTRO)
Official Title: 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
Secondary IDs:
Study Status
Record Verification: July 2018 October 2018
Overall Status: Active, not recruiting Completed
Study Start: October 12, 2016
Primary Completion: September 24 25, 2018 [ Anticipated Actual]
Study Completion: September 24 25, 2018 [ Anticipated Actual]
First Submitted: August 16, 2016
First Submitted that
Met QC Criteria:
September 8, 2016
First Posted: September 13, 2016 [Estimate]
Last Update Submitted that
Met QC Criteria:
July 5, 2018 October 9, 2018
Last Update Posted: July 6 October 10, 2018 [Actual]
Sponsor/Collaborators
Sponsor: AstraZeneca
Responsible Party: Sponsor
Collaborators:
Oversight
U.S. FDA-regulated Drug:
U.S. FDA-regulated Device:
Data Monitoring: Yes
Study Description
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.
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.

Conditions
Conditions: Asthma
Keywords: inhaled
TLR9 agonist
withdrawal design
loss of control
Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 2
Interventional Study Model: Parallel Assignment
Number of Arms: 2
Masking: QuadrupleParticipant, Care Provider, Investigator, Outcomes Assessor
Allocation: Randomized
Enrollment: 81 [Actual]
Arms and Interventions
Arms Assigned Interventions
Experimental: AZD1419
Dose adaption of AZD1419, 4 mg or 8 mg or 1 mg based on occurence of AE's
Drug: AZD1419
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
Placebo Comparator: Placebo
Matching placebo
Drug: 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
Outcome Measures
Primary Outcome Measures:
1. Time to Loss of control

Loss of asthma control is defined as any of the following:

  1. An increase of ACQ-5 to 1.5 or more
  2. A reduction of 30% or more in morning peak expiratory flow (PEF) from baseline on 2 consecutive days
  3. At least six additional reliever inhalations of SABA in a 24-hour period relative to baseline on 2 consecutive days
  4. An exacerbation requiring systemic corticosteroids


[Time Frame: Up to 52 weeks]
Secondary Outcome Measures:
2. Proportion of patients who experience loss of asthma control

Loss of asthma control is defined as any of the following:

  1. An increase of ACQ-5 to 1.5 or more
  2. A reduction of 30% or more in morning peak expiratory flow (PEF) from baseline on 2 consecutive days
  3. At least six additional reliever inhalations of SABA in a 24-hour period relative to baseline on 2 consecutive days
  4. An exacerbation requiring systemic corticosteroids


[Time Frame: Up to 52 weeks]
3. Changes over the course of the study in ACQ-5
Weekly assessment of Asthma questionaire

[Time Frame: Up to 52 weeks]
4. Changes over the course of the study in asthma daily diary score
Asthma Daily Diary recordings (twice daily) in ePRO device

[Time Frame: Up to 52 weeks]
5. Changes over the course of the study in number of moderate and severe exacerbations
Up to 52 weeks
6. Changes over the course of the study in the use of reliever bronchodilator (short-acting beta-agonist SABA)
Use of reliever medication recorded twice daily in the ePRO device

[Time Frame: Up to 52 weeks]
7. Changes over the course of the study in pre- and post-bronchodilator FEV1
Up to 52 weeks
8. Changes over the course of the study in PEF
PEF recordings twice daily captured in the ePRO device.

[Time Frame: Up to 52 weeks]
9. Changes over the course of the study inFeNO
Assessed weekly in the clinic as well as captured by the patient every other day in a handheld device

[Time Frame: Up to 52 weeks]
10. Adverse events, vital signs, ECG and laboratory parameters
Up to 52 weeks
11. Weekly peak expiratory flow rate (PEFR)
Up to 52 weeks
12. Lung diffusion capacity (DLco)
Up to 52 weeks
Eligibility
Minimum Age: 18 Years
Maximum Age: 99 Years
Sex: All
Gender Based:
Accepts Healthy Volunteers: No
Criteria:

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
Contacts/Locations
Locations: Denmark
Research Site
Hvidovre, Denmark, 2650
Research Site
København NV, Denmark, 2400
Research Site
Naestved, Denmark
Research Site
Odense C, Denmark, 5000
Hungary
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
Poland
Research Site
Lubin, Poland, 59-300
Research Site
Łódź, Poland, 90-153
Sweden
Research Site
Linköping, Sweden, 587 58
Research Site
Lund, Sweden, 221 85
Research Site
Stockholm, Sweden, 141 86
IPDSharing
Plan to Share IPD:
References
Citations:
Links:
Available IPD/Information:

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