A Phase II Study to Evaluate the Efficacy, Safety and Tolerability of AZD5069 in Patients With Uncontrolled Persistent Asthma. (NIMBUS)

A 6-month, Randomised, Double-blind, Placebo-controlled, Multi-centre, Parallel-group, Phase II Study With an Optional Safety Extension Treatment Period up to 6 Months, to Evaluate the Efficacy, Safety, and Tolerability of 3 Different Doses of AZD5069 Twice Daily as Add-on Treatment to Medium to High Dose Inhaled Corticosteroids (ICS) and Long-acting β2 Agonists (LABA), in Patients With Uncontrolled Persistent Asthma

The purpose is to Evaluate the Efficacy, Safety, and Tolerability of 3 Different Doses of AZD5069 Twice Daily as Add-on Treatment to Medium to High Dose Inhaled Corticosteroids (ICS) and Long-acting β2 Agonists (LABA), in Patients with Uncontrolled Persistent Asthma

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Drug: AZD5069; Drug: Placebo

Detailed Description

A 6-month, Randomised, Double-blind, Placebo-controlled, Multi-centre, Parallel-group, Phase II Study with an Optional Safety Extension Treatment Period up to 6 months, to Evaluate the Efficacy, Safety, and Tolerability of 3 Different Doses of AZD5069 Twice Daily as Add-on Treatment to Medium to High Dose Inhaled Corticosteroids (ICS) and Long-acting β2 Agonists (LABA), in Patients with Uncontrolled Persistent Asthma

• Study Type: Interventional
• Enrollment (Actual): 1147
• Phase: Phase 2

Contacts and Locations

Study Locations

• Bulgaria
  • Gotse Delchev, Bulgaria
    • Research Site
  • Kozloduy, Bulgaria
    • Research Site
  • Petrich, Bulgaria
    • Research Site
  • Pleven, Bulgaria
    • Research Site
  • Razgrad, Bulgaria
    • Research Site
  • Ruse, Bulgaria
    • Research Site
  • Sofia, Bulgaria
    • Research Site
  • Vidin, Bulgaria
    • Research Site
• Canada
  • Quebec, Canada
    • Research Site
  • Newfoundland and Labrador
    • Mount Pearl, Newfoundland and Labrador, Canada
      • Research Site
  • Ontario
    • Hamilton, Ontario, Canada
      • Research Site
    • Toronto, Ontario, Canada
      • Research Site
  • Quebec
    • Montreal, Quebec, Canada
      • Research Site
    • Saint-Romuald, Quebec, Canada
      • Research Site
• Czech Republic
  • Brno, Czech Republic
    • Research Site
  • Jindrichuv Hradec, Czech Republic
    • Research Site
  • Karlovy Vary, Czech Republic
    • Research Site
  • Kutna Hora, Czech Republic
    • Research Site
  • Melnik, Czech Republic
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  • Praha 5, Czech Republic
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  • Praha 6, Czech Republic
    • Research Site
  • Strakonice, Czech Republic
    • Research Site
  • Tabor, Czech Republic
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• Germany
  • Berlin, Germany
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  • Großhansdorf, Germany
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  • Hamburg, Germany
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  • Hannover, Germany
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  • München, Germany
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• Hungary
  • Aszód, Hungary
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  • Baja, Hungary
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  • Balassagyarmat, Hungary
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  • Budapest, Hungary
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  • Cegléd, Hungary
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  • Gyula, Hungary
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  • Komárom, Hungary
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  • Makó, Hungary
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  • Monor, Hungary
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  • Nyíregyháza, Hungary
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  • Pécs, Hungary
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  • Szeged, Hungary
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  • Szombathely, Hungary
    • Research Site
  • Százhalombatta, Hungary
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• Mexico
  • Guadalajara, Mexico
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  • Mexico, Mexico
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  • Monterrey, Mexico
    • Research Site
• Poland
  • Białystok, Poland
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  • Gdańsk, Poland
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  • Giżycko, Poland
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  • Kraków, Poland
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  • Lublin, Poland
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  • Poznań, Poland
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  • Proszowice, Poland
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  • Skierniewice, Poland
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  • Tarnów, Poland
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  • Wrocław, Poland
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  • Łódź, Poland
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  • Żnin, Poland
    • Research Site
• Romania
  • Brasov, Romania
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  • Bucharest, Romania
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  • Constanta, Romania
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  • Deva, Romania
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  • Iasi, Romania
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• Russian Federation
  • Ekaterinburg, Russian Federation
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  • Izhevsk, Russian Federation
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  • Kazan, Russian Federation
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  • Moscow, Russian Federation
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  • Saint Petersburg, Russian Federation
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  • Saint-Petersburg, Russian Federation
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  • St. Petersburg, Russian Federation
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  • Vladikavkaz, Russian Federation
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  • Yaroslavl, Russian Federation
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• Slovakia
  • Bardejov, Slovakia
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  • Bratislava, Slovakia
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  • Komarno, Slovakia
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  • Kosice, Slovakia
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  • Levice, Slovakia
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  • Poprad, Slovakia
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  • Spisska Nova Ves, Slovakia
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  • Surany, Slovakia
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  • Topolcany, Slovakia
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  • Trencin, Slovakia
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  • Zvolen, Slovakia
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• South Africa
  • Amanzimtoti, South Africa
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  • Cape Town, South Africa
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  • Durban, South Africa
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  • Pretoria, South Africa
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  • Umkomaas, South Africa
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• Ukraine
  • Donetsk, Ukraine
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  • Ivano-Frankivsk, Ukraine
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  • Kharkiv, Ukraine
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  • Kyiv, Ukraine
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  • Vinnytsia, Ukraine
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  • Zaporizhzhya, Ukraine
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  • Zaporizhzhzya, Ukraine
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  • Zaporozye, Ukraine
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• United Kingdom
  • Birmingham, United Kingdom
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  • Dundee, United Kingdom
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  • Liverpool, United Kingdom
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  • London, United Kingdom
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 150 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Men and women aged 18 years and above. Females of childbearing potential must use a highly effective contraceptive method plus a condom by their male partner.
• Diagnosis of asthma for at least 12 months (GINA 2011)
• Uncontrolled persistent asthma, despite treatment with medium to high dose ICS and LABA, and with a history of exacerbations during the last year
• Morning prebronchodilator FEV1 of ≥30% and ≤85% predicted normal at enrolment
• Daily use of medium or high dose ICS (≥fluticasone 500 µg or the equivalent daily)

Exclusion Criteria:

• Any clinically significant disease or disorder (including any chronic lower respiratory disease other than asthma) that may put the patient at risk or influence study results
• Patients with recurrent, latent, or chronic infections
• Active tuberculosis or latent tuberculosis without completion of an appropriate course of treatment or prophylactic treatment
• Significant lower respiratory tract infection not resolved within 30 days prior to enrolment
• Current smoker or smoking history of more than 20 pack years

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AZD5069 5 mg; AZD5069 oral capsules self-administered twice daily	Drug: AZD5069; AZD5069 oral capsules self-administered twice daily.
Experimental: AZD5069 15 mg; AZD5069 oral capsules self-administered twice daily	Drug: AZD5069; AZD5069 oral capsules self-administered twice daily.
Experimental: AZD5069 45 mg; AZD5069 oral capsules self-administered twice daily	Drug: AZD5069; AZD5069 oral capsules self-administered twice daily.
Placebo Comparator: Placebo; Placebo oral capsules self-administered twice daily	Drug: Placebo; Placebo oral capsules self-administered twice daily.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Rate of Severe Asthma Exacerbations During 6 Months	From start of treatment up to 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of Asthma-specific Hospital Admission/Intensive Care Unit Admissions During 6 Months		From start of treatment up to 6 months
Total Number of Days of Asthma-specific Hospital Admission/Intensive Care Unit Admissions		From start of treatment up to 6 months
Total Number of Days on Oral Cortecosteroids, Due to a Worsening of Asthma Symptoms		From start of treatment up to 6 months
Change From Baseline to 2 Weeks Measurement of Pre-bronchodilator FEV1	Only patients with both a non-missing value at baseline and visit at two weeks are included in the analysis	Baseline (Day 0) and 2 weeks after Day 0
Change From Baseline to 1 Month Measurement of Pre-bronchodilator FEV1	Only patients with both a non-missing value at baseline and visit at one month are included in the analysis	Baseline (Day 0) and 1 month after Day 0
Change From Baseline to 2 Months Measurement of Pre-bronchodilator FEV1	Only patients with both a non-missing value at baseline and visit at two months are included in the analysis	Baseline (Day 0) and 2 months after Day 0
Change From Baseline to 3 Months Measurement of Pre-bronchodilator FEV1	Only patients with both a non-missing value at baseline and visit at three months are included in the analysis	Baseline (Day 0) and 3 months after Day 0
Change From Baseline to 4 Months Measurement of Pre-bronchodilator FEV1	Only patients with both a non-missing value at baseline and visit at four months are included in the analysis	Baseline (Day 0) and 4 months after Day 0
Change From Baseline to 6 Months Measurement of Pre-bronchodilator FEV1	Only patients with both a non-missing value at baseline and visit at six months are included in the analysis	Baseline (Day 0) and 6 months after Day 0
Change From Baseline to 2 Weeks Measurement of Post-bronchodilator FEV1	Only patients with both a non-missing value at baseline and visit at two weeks are included in the analysis	Baseline (Day 0) and 2 weeks after Day 0
Change From Baseline to 1 Month Measurement of Post-bronchodilator FEV1	Only patients with both a non-missing value at baseline and visit at one month are included in the analysis	Baseline (Day 0) and 1 month after Day 0
Change From Baseline to 2 Months Measurement of Post-bronchodilator FEV1	Only patients with both a non-missing value at baseline and visit at two months are included in the analysis	Baseline (Day 0) and 2 months after Day 0
Change From Baseline to 3 Months Measurement of Post-bronchodilator FEV1	Only patients with both a non-missing value at baseline and visit at three months are included in the analysis	Baseline (Day 0) and 3 months after Day 0
Change From Baseline to 4 Months Measurement of Post-bronchodilator FEV1	Only patients with both a non-missing value at baseline and visit at four months are included in the analysis	Baseline (Day 0) and 4 months after Day 0
Change From Baseline to 6 Months Measurement of Post-bronchodilator FEV1	Only patients with both a non-missing value at baseline and visit at six months are included in the analysis	Baseline (Day 0) and 6 months after Day 0
Change From Baseline to Overall Mean of Treatment Period in ACQ-5 (Asthma Control Questionnaire, 5-item Version) Total Score	The ACQ-5 is a validated questionnaire consisting of 5 items for the assessment of asthma symptom which are night symptom, morning symptom, limitation for the activities, shortness of breath, and wheeze. Each item is graded on a scale of 0-6 and the questions are equally weighted. The ACQ-5 score is the mean of the 5 questions and therefore between 0 (totally controlled) and 6 (severely uncontrolled).	Baseline (Day 0), Treatment Period (1,2,3,4, and 6 months)
Number of Patients Presenting Improvement From Baseline to End of Treatment Period in ACQ-5 (Asthma Control Questionnaire, 5-item Version)	The ACQ-5 is a validated questionnaire consisting of 5 items for the assessment of asthma symptom which are night symptom, morning symptom, limitation for the activities, shortness of breath, and wheeze. Each item is graded on a scale of 0-6 and the questions are equally weighted. The ACQ-5 score is the mean of the 5 questions and therefore between 0 (totally controlled) and 6 (severely uncontrolled).	Baseline (Day 0) and 6 months after Day 0
Change From Baseline to Overall Mean of Treatment Period in AQLQ(S) (Asthma Quality of Life Questionnaire Standardised Version) Overall Score	The AQLQ is a 32-item disease specific questionnaire designed to measure functional impairments in asthma. Patients are asked to score each item on a 7-point scale based on the experience of last 2 weeks. The overall AQLQ score is the mean response to all 32 questions. Therefore, the possible highest score (better) would be 7 and the lowest (worse) would be 1. Changes in scores of 0.5 to 1.0 are considered clinically meaningful; 1.0 to 1.5 as moderate and > 1.5 as marked clinically important differences for any individual domain or for the overall summary score.	Baseline (Day 0), Treatment Period (1,3, and 6 months)
Number of Patients Presenting Improvement From Baseline to End of Treatment Period in AQLQ(S) (Asthma Quality of Life Questionnaire Standardised Version) Overall Score	The AQLQ is a 32-item disease specific questionnaire designed to measure functional impairments in asthma. Patients are asked to score each item on a 7-point scale based on the experience of last 2 weeks. The overall AQLQ score is the mean response to all 32 questions. Therefore, the possible highest score (better) would be 7 and the lowest (worse) would be 1. Changes in scores of 0.5 to 1.0 are considered clinically meaningful; 1.0 to 1.5 as moderate and > 1.5 as marked clinically important differences for any individual domain or for the overall summary score.	Baseline (Day 0) and 6 months after Day 0
Change From Baseline to Treatment Period (Day 1 to Day 28) for Astma Symptom Free Days		Baseline (last 14 days before randomization) and Treatment Period (Days 1 to 28)
Change From Baseline to Treatment Period (Day 29 to Day 56) for Astma Symptom Free Days		Baseline (last 14 days before randomization) and Treatment Period (Days 29 to 56)
Change From Baseline to Treatment Period (Day 57 to Day 84) for Asthma Symptom Free Days		Baseline (last 14 days before randomization) and Treatment Period (Days 57 to 84)
Change From Baseline to Treatment Period (Day 85 to End of Treatment [6 Months]) for Asthma Symptom Free Days		Baseline (last 14 days before randomization) and Treatment Period (Day 85 to 6 months)
Change From Baseline to Treatment Period (Day 1 to Day 28) for Asthma Control Days		Baseline (last 14 days before randomization) and Treatment Period (Days 1 to 28)
Change From Baseline to Treatment Period (Day 29 to Day 56) for Asthma Control Days		Baseline (last 14 days before randomization) and Treatment Period (Days 29 to 56)
Change From Baseline to Treatment Period (Day 57 to Day 84) for Asthma Control Days		Baseline (last 14 days before randomization) and Treatment Period (Days 57 to 84)
Change From Baseline to Treatment Period (Day 85 to End of Treatment [6 Months]) for Asthma Control Days		Baseline (last 14 days before randomization) and Treatment Period (Days 85 to 6 months
Change From Baseline to Treatment Period (Day 1 to Day 28) for Use of Rescue Medication Free Days		Baseline (last 14 days before randomization) and Treatment Period (Days 1 to 28)
Change From Baseline to Treatment Period (Day 29 to Day 56) for Use of Rescue Medication Free Days		Baseline (last 14 days before randomization) and Treatment Period (Days 29 to 56)
Change From Baseline to Treatment Period (Day 57 to Day 84) for Use of Rescue Medication Free Days		Baseline (last 14 days before randomization) and Treatment Period (Days 57 to 84)
Change From Baseline to Treatment Period (Day 85 to End of Treatment [6 Months]) for Use of Rescue Medication Free Days		Baseline (last 14 days before randomization) and Treatment Period (Days 85 to 6 months)
Change From Baseline to Treatment Period (Day 1 to Day 28) for Night Time Awakenings Due to Asthma Symptoms		Baseline (last 14 days before randomization) and Treatment Period (Days 1 to 28)
Change From Baseline to Treatment Period (Day 29 to Day 56) for Night Time Awakenings Due to Asthma Symptoms		Baseline (last 14 days before randomization) and Treatment Period (Day 29 to Day 56)
Change From Baseline to Treatment Period (Day 57 to Day 84) for Night Time Awakenings Due to Asthma Symptoms		Baseline (last 14 days before randomization) and Treatment Period (Day 57 to Day 84)
Change From Baseline to Treatment Period (Day 85 to End of Treatment [6 Months]) for Night Time Awakenings Due to Asthma Symptoms		Baseline (last 14 days before randomization) and Treatment Period (Day 85 to 6 months)
Number of Participants With Well Controlled Asthma Weeks at Baseline		Last 2 weeks before randomization
Number of Well Controlled Asthma Weeks During Treatment		Day 1to end of the 6 months treatment period
Number of Participants With Uncontrolled Persistent Asthma Weeks at Baseline		Last 2 weeks before randomization
Number of Uncontrolled Persistent Asthma Weeks During Treatment		Day 1 to end of the 6 months treatment period
Mean Plasma Concentration of AZD5069 at Day 7		Day 7
Mean Plasma Concentration of AZD5069 at 1 Month		at 1 month

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Study Director: Bengt Larsson, MEDICAL SCIENCE DIRECTOR, AZ Mondal R&D, Sweden

Publications and helpful links

General Publications

• O'Byrne PM, Metev H, Puu M, Richter K, Keen C, Uddin M, Larsson B, Cullberg M, Nair P. Efficacy and safety of a CXCR2 antagonist, AZD5069, in patients with uncontrolled persistent asthma: a randomised, double-blind, placebo-controlled trial. Lancet Respir Med. 2016 Oct;4(10):797-806. doi: 10.1016/S2213-2600(16)30227-2. Epub 2016 Aug 27.

Study record dates

Study Major Dates

• Study Start: November 1, 2012
• Primary Completion (Actual): August 1, 2014
• Study Completion (Actual): August 1, 2014

Study Registration Dates

• First Submitted: October 9, 2012
• First Submitted That Met QC Criteria: October 9, 2012
• First Posted (Estimate): October 11, 2012

Study Record Updates

• Last Update Posted (Estimate): March 1, 2016
• Last Update Submitted That Met QC Criteria: February 1, 2016
• Last Verified: February 1, 2016

More Information

Terms related to this study

• Keywords: Safety; Uncontrolled Asthma,; Exacerbation,
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma
• Other Study ID Numbers: D3551C00001; 2012-001869-33