Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Study to Evaluate Tezepelumab in Adults & Adolescents With Severe Uncontrolled Asthma (NAVIGATOR)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03347279
Recruitment Status : Active, not recruiting
First Posted : November 20, 2017
Last Update Posted : September 17, 2019
Sponsor:
Collaborator:
Amgen
Information provided by (Responsible Party):
AstraZeneca

Brief Summary:
A Multicentre, Randomized, Double-Blind, Placebo Controlled, Parallel Group, Phase 3 Study to Evaluate the Efficacy and Safety of Tezepelumab in Adults and Adolescents with Severe Uncontrolled Asthma

Condition or disease Intervention/treatment Phase
Asthma Biological: Experimental: Tezepelumab Other: Placebo Phase 3

Detailed Description:
This is a multicentre, randomized, double-blind, placebo controlled, parallel group study designed to evaluate the efficacy and safety of tezepelumab in adults and adolescents with severe, uncontrolled asthma on medium to high-dose ICS and at least one additional asthma controller medication with or without OCS. Approximately 1060 subjects will be randomized globally. Subjects will receive tezepelumab, or placebo, administered via subcutaneous injection at the study site, over a 52-week treatment period. The study also includes a post-treatment follow-up period of 12 weeks.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1032 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Subjects will be randomized in a 1:1 ratio to either tezepelumab or matching placebo both administered subcutaneously.
Masking: Triple (Participant, Care Provider, Investigator)
Masking Description: Double-Blind
Primary Purpose: Treatment
Official Title: A Multicentre, Randomized, Double-Blind, Placebo Controlled, Parallel Group, Phase 3 Study to Evaluate the Efficacy and Safety of Tezepelumab in Adults and Adolescents With Severe Uncontrolled Asthma (NAVIGATOR)
Actual Study Start Date : November 23, 2017
Estimated Primary Completion Date : September 11, 2020
Estimated Study Completion Date : December 4, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Asthma

Arm Intervention/treatment
Experimental: Tezepelumab
Tezepelumab: Tezepelumab subcutaneous injection
Biological: Experimental: Tezepelumab
Tezepelumab subcutaneous injection
Other Name: Tezepelumab

Placebo Comparator: Placebo
Placebo: Placebo subcutaneous injection
Other: Placebo
Placebo subcutaneous injection




Primary Outcome Measures :
  1. Annualized asthma exacerbation rate (AERR) [ Time Frame: Baseline to Week 52 ]
    The annualized exacerbation rate is based on exacerbations reported by the investigator in the eCRF over 52 weeks.


Secondary Outcome Measures :
  1. Change from baseline in pre-dose/pre-bronchodilator (pre-BD) forced expiratory volume in 1 second (FEV1) [ Time Frame: Baseline, Week 52 ]
    Change from baseline in FEV1 as compared to placebo at Week 52. FEV1 is defined as the volume of air exhaled from the lungs in the first second of a forced expiration.

  2. Change from baseline in Standardized Asthma Quality of Life Questionnaire for 12 years and older (AQLQ(S)+12) total score [ Time Frame: Baseline, Week 52 ]
    Change from baseline in AQLQ(S)+12 as compared to placebo at Week 52. The AQLQ(S)+12 is a questionnaire that measures the health-related quality of life experienced by asthma subjects. The total score is defined as the average of all 32 questions in the AQLQ(S)+12 questionnaire. AQLQ(S)+12 is a 7-point scale questionnaire, ranging from 7 (no impairment) to 1 (severe impairment).

  3. Change from baseline in Asthma Control Questionnaire-6 (ACQ-6) Score [ Time Frame: Baseline, Week 52 ]
    Change from baseline in ACQ-6 as compared to placebo at Week 52. The ACQ-6 captures asthma symptoms and short-acting β2-agonist use via subject-report. Questions are weighted equally and scored from 0 (totally controlled) to 6 (severely uncontrolled). The ACQ-6 score is the mean of the responses.

  4. Change from baseline in weekly mean daily Asthma Symptom Diary score [ Time Frame: Baseline, Week 52 ]

    Change from baseline in Asthma Symptom Diary score as compared to placebo at Week 52.

    The Asthma Symptom Diary comprises of 10 items (5 items in the morning; 5 items in the evening). Asthma symptoms during night time and daytime are recorded by the patient each morning and evening in the daily diary. A daily ASD score is the mean of the 10 items. Responses for all 10 items are required to calculate the daily ASD score; otherwise, it is treated as missing. For the 7-day average asthma symptom score, scoring is done with no imputation using the mean of at least 4 of the 7 daily ASD scores as a mean weekly item score. The 7-day average ASD score ranges from 0 to 4.


  5. Time to first asthma exacerbation [ Time Frame: Baseline to Week 52 ]
    Time to the first occurrence of asthma exacerbation post randomisation

  6. Change from baseline in fractional exhaled nitric oxide FENO (ppb) [ Time Frame: Baseline, Week 52 ]
    Change from baseline in FeNO at week 52.

  7. Change from baseline in weekly mean rescue medication use [ Time Frame: Baseline, Week 52 ]
    Change from baseline in weekly mean rescue medication use at Week 52. The number of rescue medication inhalations (puffs) and nebulizer treatments taken will be recorded by the subject in the Asthma Symptom Diary twice daily (i.e., in the morning and evening). Each timepoint is calculated as weekly means based on daily diary data.

  8. Work Productivity and Activity Impairment (WPAI+CIQ) Questionnaire and Classroom Impairment Questionnaire score [ Time Frame: Week 52 ]
    WPAI+CIQ score at Week 52. The WPAI+CIQ consists of questions about how asthma and asthma related issues impact a subject's ability to work, attend classes, and perform regular daily activities.

  9. Serum trough concentrations [ Time Frame: Baseline to Week 52 ]
    Serum trough concentrations at each scheduled visit

  10. European Quality of Life - 5 Dimensions 5 Levels Questionnaire (EQ-5D-5L) score [ Time Frame: Week 52 ]
    EQ-5D at Week 52. The EQ-5D-5L questionnaire assesses 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 response options (no problems, slight problems, moderate problems, severe problems, and extreme problems) that reflect increasing levels of difficulty.

  11. Patient Global Impression of Change/Severity (PGI-C, PGI-S) and Clinician Global Impression of Change (CGI-C) [ Time Frame: Week 52 ]
    The CGI-C and the PGI-C are used to evaluate the overall response to treatment, and the assessments use a 7-point rating scale ranging from 1 (Very Much Improved) to 7 (Very Much Worse). PGI-S is a single item designed to capture the subject's perception of overall symptom severity using a 6-point categorical response scale (no symptoms to very severe symptoms)

  12. Change from baseline in peripheral blood eosinophils [ Time Frame: Baseline, Week 52 ]
    Change from baseline in blood eosinophil counts at week 52.

  13. Change from baseline in total serum IgE [ Time Frame: Baseline, Week 52 ]
    Change from baseline in IgE at week 52.

  14. Asthma specific resource utilization (eg, unscheduled physician visits, unscheduled phone calls to physicians, use of other asthma medications) [ Time Frame: Baseline, Week 52 ]
    Number of asthma specific resource utilizations (e.g. unscheduled physician visits, unscheduled phone calls to physicians, use of other asthma medications) over 52 weeks

  15. Change from baseline in weekly mean morning and evening peak expiratory flow (PEF) [ Time Frame: Baseline, Week 52 ]
    Change from baseline in weekly mean morning and evening peak expiratory flow (PEF) at Week 52. Home PEF testing will be performed by the subject in the morning upon awakening and in the evening at bedtime using an electronic, hand-held spirometer. Each timepoint is calculated as weekly means.

  16. Change from baseline in weekly mean number of night time awakenings [ Time Frame: Baseline, Week 52 ]
    Change from baseline in weekly mean number of night time awakenings at Week 52. Each timepoint is calculated as weekly mean number of awakenings due to asthma based on daily diary data.

  17. Immunogenicity anti-drug antibodies [ Time Frame: Baseline to Week 52 ]
    Incidence of anti-drug antibodies over 52 weeks.

  18. Proportion of subjects with >=1 asthma exacerbation [ Time Frame: Baseline to Week 52 ]
    Number and percentage of patients with at least one post randomisation asthma exacerbation

  19. Annualized rate of exacerbations associated with emergency room visit, urgent care visit, or hospitalization [ Time Frame: Baseline to Week 52 ]
    The annualized exacerbation rate is based on exacerbations reported by the investigator that are associated with an emergency room visit, urgent care visit, or a hospitalization



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   12 Years to 80 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age. 12-80
  • Documented physician-diagnosed asthma for at least 12 months
  • Subjects who have received a physician-prescribed asthma controller medication with medium or high dose ICS for at least 12 months.
  • Documented treatment with a total daily dose of either medium or high dose ICS (≥ 500 µg fluticasone propionate dry powder formulation equivalent total daily dose) for at least 3 months.
  • At least one additional maintenance asthma controller medication is required according to standard practice of care and must be documented for at least 3 months.
  • Morning pre-BD FEV1 <80% predicted normal (<90% for subjects 12-17 yrs)
  • Evidence of asthma as documented by either: Documented historical reversibility of FEV1 ≥12% and ≥200 mL in the previous 12 months OR Post-BD (albuterol/salbutamol) reversibility of FEV1 ≥12% and ≥200 mL during screening.
  • Documented history of at least 2 asthma exacerbation events within 12 months.
  • ACQ-6 score ≥1.5 at screening and on day of randomization

Exclusion Criteria:

  • Pulmonary disease other than asthma.
  • History of cancer.
  • History of a clinically significant infection.
  • Current smokers or subjects with smoking history ≥10 pack-years and subjects using vaping products, including electronic cigarettes.
  • History of chronic alcohol or drug abuse within 12 months.
  • Hepatitis B, C or HIV.
  • Pregnant or breastfeeding.
  • History of anaphylaxis following any biologic therapy.
  • Subject randomized in the current study or previous tezepelumab studies.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03347279


  Show 291 Study Locations
Sponsors and Collaborators
AstraZeneca
Amgen
Investigators
Layout table for investigator information
Principal Investigator: Andrew Menzies-Gow, MD Royal Brompton Hospital, United Kingdom

Layout table for additonal information
Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT03347279     History of Changes
Other Study ID Numbers: D5180C00007
First Posted: November 20, 2017    Key Record Dates
Last Update Posted: September 17, 2019
Last Verified: September 2019

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by AstraZeneca:
Asthma, Uncontrolled Asthma, Severe Uncontrolled Asthma
Additional relevant MeSH terms:
Layout table for MeSH terms
Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs