Study to Evaluate Tezepelumab in Adults With Severe Uncontrolled Asthma (DIRECTION)

June 13, 2025 updated by: AstraZeneca

A Regional, Multicentre, Randomized, Double-Blind, Placebo Controlled, Parallel Group, Phase 3 Study to Evaluate the Efficacy and Safety of Tezepelumab in Adults With Severe Uncontrolled Asthma

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This is a regional, multicentre, randomized, double-blind, placebo controlled, parallel group, phase 3 study designed to evaluate the efficacy and safety of 210 mg Q4W (SC) of tezepelumab in adults with severe, uncontrolled asthma on medium to high-dose ICS and at least one additional asthma controller medication with or without OCS. Approximately 396 participants will be randomized regionally (China/non-China). Participants 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

Study Type

Interventional

Enrollment (Actual)

405

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
      • Baotou, China, 14010
        • Research Site
      • Beijing, China, 100070
        • Research Site
      • Beijing, China, 100020
        • Research Site
      • Beijing, China, 100730
        • Research Site
      • Beijing, China, 100853
        • Research Site
      • Beijing, China, 100029
        • Research Site
      • Beijing, China, 1000096
        • Research Site
      • Changchun, China, 130021
        • Research Site
      • Changsha, China, 410011
        • Research Site
      • Changsha, China, 410008
        • Research Site
      • Chengdu, China, 610041
        • Research Site
      • Chongqing, China, 400038
        • Research Site
      • Chongqing, China, 400016
        • Research Site
      • Chongqing, China, 400000
        • Research Site
      • Fuzhou, China, 350001
        • Research Site
      • Guangzhou, China, 510120
        • Research Site
      • Guangzhou, China
        • Research Site
      • Guangzhou, China, 510080
        • Research Site
      • Guangzhou, China, 510515
        • Research Site
      • Guiyang, China, 550004
        • Research Site
      • Haikou, China, 570311
        • Research Site
      • Hangzhou, China, 310020
        • Research Site
      • Hefei, China, 133500
        • Research Site
      • Hengyang, China, 421001
        • Research Site
      • Hohhot, China, 010017
        • Research Site
      • Hohhot, China, 10050
        • Research Site
      • Huzhou, China, 313003
        • Research Site
      • Jinan, China, 250013
        • Research Site
      • Jinhua, China, 321000
        • Research Site
      • Kunming, China, 650032
        • Research Site
      • Lanzhou, China, 730000
        • Research Site
      • Linhai, China, 317000
        • Research Site
      • Linyi, China, CN-276003
        • Research Site
      • Nanchang, China, 330006
        • Research Site
      • Nanjing, China, 2100008
        • Research Site
      • Nanjing, China, 210009
        • Research Site
      • Nanjing, China, 210029
        • Research Site
      • Nanning, China, 530007
        • Research Site
      • Quanzhou, China, 362000
        • Research Site
      • Shanghai, China, 200032
        • Research Site
      • Shanghai, China, 200025
        • Research Site
      • Shanghai, China, 200050
        • Research Site
      • Shengyang, China, 110004
        • Research Site
      • Shenyang, China, 110015
        • Research Site
      • Shenzhen, China, 518035
        • Research Site
      • Shijiazhuang, China, 050000
        • Research Site
      • Tianjin, China, 300192
        • Research Site
      • Urumchi, China, 830054
        • Research Site
      • Weifang, China, 261041
        • Research Site
      • Wenzhou, China, 325027
        • Research Site
      • Wuhan, China, 430022
        • Research Site
      • Wuhan, China, 430030
        • Research Site
      • Wuhan, China, 430033
        • Research Site
      • Xi'an, China, 710004
        • Research Site
      • Xining, China, 810007
        • Research Site
      • Xuzhou, China, 221009
        • Research Site
      • Xuzhou, China, 221000
        • Research Site
      • Yangzhou, China, 225001
        • Research Site
      • Zhengzhou, China, 450000
        • Research Site
      • Zhuhai, China, 519099
        • Research Site
      • Zibo, China, 255036
        • Research Site
      • Zunyi, China, 563100
        • Research Site
  • Korea, Republic of
      • Cheongju-si, Korea, Republic of, 28644
        • Research Site
      • Daegu, Korea, Republic of, 42415
        • Research Site
      • Jeonju-si, Korea, Republic of, 54907
        • Research Site
      • Seoul, Korea, Republic of, 03722
        • Research Site
      • Seoul, Korea, Republic of, 05505
        • Research Site
      • Seoul, Korea, Republic of, 06591
        • Research Site
      • Seoul, Korea, Republic of, 03312
        • Research Site
      • Suwon-si, Korea, Republic of, 16499
        • Research Site
  • Philippines
      • Iloilo City, Philippines, 5000
        • Research Site
      • Quezon City, Philippines, 1100
        • Research Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Age. 18-80
  • Documented physician-diagnosed asthma for at least 12 months
  • Participants who have received a physician-prescribed asthma controller medication with medium or high dose ICS for at least 6 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
  • 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, and at least one of the exacerbations should occur during the treatment of medium-to-high dose ICS.
  • 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 participants with smoking history ≥10 pack-yrs.
  • 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.
  • participant randomized in the current study or previous tezepelumab studies.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Tezepelumab
Tezepelumab: Tezepelumab subcutaneous injection
Biological: Experimental: Tezepelumab
Tezepelumab subcutaneous injection
Other Names:
  • Tezepelumab
Placebo Comparator: Placebo
Placebo: Placebo subcutaneous injection
Other: Placebo
Placebo subcutaneous injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Annual Asthma Exacerbation Rate (AERR)
Time Frame: Randomization to Week 52
The annual exacerbation rate is based on exacerbations reported by the investigator in the eCRF over 52 weeks
Randomization to Week 52

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Mean Change From Baseline in Pre-dose/Pre-bronchodilator (Pre-BD) Forced Expiratory Volume in 1 Second (FEV1) at Week 52
Time Frame: Randomization to Week 52
Mean 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.
Randomization to Week 52
Mean Change From Baseline in Standardized Asthma Quality of Life Questionnaire for 12 Years and Older (AQLQ(S)+12) Total Score at Week 52
Time Frame: Randomization to Week 52
Mean 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 participants. 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).
Randomization to Week 52
Mean Change From Baseline in Asthma Control Questionnaire-6 (ACQ-6) Score at Week 52
Time Frame: Randomization to Week 52
Mean 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.
Randomization to Week 52
Mean Change From Baseline in Weekly Mean Daily Asthma Symptom Diary Score at Week 52
Time Frame: Randomization to Week 52
Mean 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. A higher value indicates a worse outcome. 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.
Randomization to Week 52
Time to First Asthma Exacerbation
Time Frame: Randomization to Week 52
Time to the first occurrence of asthma exacerbation post randomization, presented as number of participants with at least one asthma exacerbation reported in the eCRF
Randomization to Week 52
Mean Change From Baseline in Fractional Exhaled Nitric Oxide at Week 52
Time Frame: Randomization to Week 52
Mean change from baseline in FENO (ppb) at week 52 to assess the effect of 210 mg of tezepelumab SC Q4W on biomarkers
Randomization to Week 52
Number of Participants With Asthma Specific Resource Utilization Over 52 Weeks
Time Frame: Randomization to Week 52
Number of participants with asthma specific resource utilization (e.g. unscheduled physician visits, unscheduled phone calls to physicians, use of other asthma medications) over 52 weeks.
Randomization to Week 52
Pharmacokinetics of Tezepelumab
Time Frame: Baseline, Week 24, Week 52, Week 64
Mean serum trough PK concentrations taken pre-dose at each scheduled visit to evaluate the pharmacokinetics (PK) of tezepelumab
Baseline, Week 24, Week 52, Week 64
Mean Change From Baseline in EQ-5D-5L VAS Score at Week 52
Time Frame: At Week 52
Mean change from baseline in EQ-5D-5L VAS at week 52. EQ-5D-5L visual analogue scale (VAS) allows participants to rate current health status on a scale of 0-100, with 0 being the worst imaginable health state.
At Week 52
Mean Change From Baseline in Blood Eosinophils (Cells/uL) at Week 52
Time Frame: Randomization to Week 52
Mean change from baseline in blood eosinophil counts at week 52 to assess the effect of 210 mg of tezepelumab SC Q4W on biomarkers.
Randomization to Week 52
Mean Change From Baseline in Total Serum IgE (IU/mL) at Week 52
Time Frame: Randomization to Week 52
Mean change from baseline in IgE at week 52 to assess the effect of 210 mg of tezepelumab SC Q4W on biomarkers.
Randomization to Week 52
Mean Change From Baseline in Night Time Awakenings (Percentage) at Week 52
Time Frame: Randomization to Week 52
Mean change from baseline in night time awakenings due to asthma at Week 52. Night time awakenings percentage is defined as number of nights with awakenings due to asthma and requiring rescue medication divided by number of nights with available data and multiplied by 100%. At least 4 out of 7 days of data is required to calculate a weekly mean.
Randomization to Week 52
Immunogenicity of Tezepelumab
Time Frame: Baseline to Week 64
Anti-drug antibodies (ADA) responses at baseline and post baseline. Persistently positive is defined as positive at >=2 post baseline assessments (with >=16 weeks between the first and the last positive) or positive at last post baseline assessment. Transiently positive is defined as having at least one post baseline ADA positive assessment and not fulfilling the conditions of persistently positive. Treatment boosted ADA defined as baseline positive ADA that was boosted to a 4 fold or higher level following treatment. Treatment emergent ADA defined as sum of treatment induced ADA and treatment boosted ADA.
Baseline to Week 64
Mean Change From Baseline in Daily Rescue Medication Use (Weekly Means) at Week 52
Time Frame: Randomization to Week 52
Daily rescue medication use is defined as: Number of night inhaler puffs + 2 x [number of night nebulizer times] + number of daytime inhaler puffs + 2 x [number of day nebulizer times]. Weekly means are calculated using at least 4 of 7 days of daily rescue medication use.
Randomization to Week 52
Mean Change From Baseline in Home Based Morning Peak Expiratory Flow (PEF) at Week 52
Time Frame: Randomization to Week 52
Mean change from baseline in home based morning PEF (L/min) at Week 52. Home PEF testing was performed by participant in the morning upon awakening and in the evening at bedtime using an electronic, hand-held spirometer. Weekly means are calculated using at least 4 of the 7 days of PEF data.
Randomization to Week 52
Mean Change From Baseline in Home Based Evening Peak Expiratory Flow (PEF) at Week 52
Time Frame: Randomization to Week 52
Mean change from baseline in home based evening PEF (L/min) at Week 52. Home PEF testing was performed by participant in the morning upon awakening and in the evening at bedtime using an electronic, hand-held spirometer. Weekly means are calculated using at least 4 of the 7 days of PEF data.
Randomization to Week 52
Annual Asthma Exacerbation Rate Resulting in Emergency Room Visit or Hospitalization
Time Frame: Randomization to Week 52
The annual exacerbation rate is based on exacerbations reported by the investigator that are associated with an emergency room visit, urgent care visit, or a hospitalization (where urgent care visit was captured as an emergency room visit on the eCRF).
Randomization to Week 52
Proportion of Participants Who Had no Asthma Exacerbations
Time Frame: Randomization to Week 52
The proportion of participants who had no asthma exacerbations is presented as the percentage of participants with no exacerbations. This is defined as participants who meet both the following criteria: (1) completed the 52 week treatment period and (2) did not report an exacerbation during this period.
Randomization to Week 52

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

AstraZeneca

Collaborators

Amgen

Investigators

  • Principal Investigator: Nanshan Zhong, Bachelor, Guangzhou institute of Respiratory Disease, China

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 14, 2019

Primary Completion (Actual)

May 24, 2024

Study Completion (Actual)

August 13, 2024

Study Registration Dates

First Submitted

April 23, 2019

First Submitted That Met QC Criteria

April 23, 2019

First Posted (Actual)

April 25, 2019

Study Record Updates

Last Update Posted (Estimated)

July 1, 2025

Last Update Submitted That Met QC Criteria

June 13, 2025

Last Verified

June 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • D5180C00021

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal.

All request will be evaluated as per the AZ disclosure commitment:

https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

IPD Sharing Time Frame

AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

IPD Sharing Access Criteria

When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

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.

Subscribe