Study to Evaluate Efficacy and Safety of Tezepelumab in Reducing Oral Corticosteroid Use in Adult Patients With Severe Asthma

AstraZeneca305 enrolled

Overview

This is a study designed to evaluate efficacy and safety of Tezepelumab in reducing oral corticosteroid use in adult patients with severe asthma who are receiving oral corticosteroids with or without additional asthma controller medications.

This is a multicentre, single-arm, phase 3b study designed to evaluate efficacy and safety of reducing daily oral corticosteroid use after initiation of 210 mg dose of Tezepelumab administered subcutaneously in patients with severe asthma receiving high-dose inhaled corticosteroid plus long-acting β2 agonist and oral corticosteroids with or without additional asthma controller medications.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

305

Conditions

Asthma

Interventions

TezepelumabBIOLOGICAL

Tezepelumab subcutaneous injection

Eligibility

Sex: ALLMin age: 18 YearsMax age: 80 Years

Medical Language ↔ Plain English

Main inclusion criteria: * Age 18-80 years. * Documented physician diagnosed asthma requiring continuous treatment with high-dose ICS plus a LABA for at least 6 months prior to Visit 1. The ICS and LABA can be contained within a combination product or given by separate inhalers. * Documented long-term OCS therapy for asthma, equivalent to a daily dose of at least 5 mg and up to 40 mg of prednisone/prednisolone for at least 3 continuous months directly preceding Visit 1. * Participant should be on a stable maintenance OCS dose for at least 4 weeks prior to Visit 1. * Documented history of at least 1 asthma exacerbation event within 12 months prior to Visit 1. Other inclusion criteria per protocol apply. Main exclusion criteria: * Pulmonary disease or systemic diseases, other than asthma associated with elevated peripheral EOS counts. * Any disorder or major physical impairment that is not stable and could affect the safety of the participant throughout the study, influence the findings of the study or the interpretation, or impede the participant's ability to complete the entire duration of study. * History of cancer. * History of a clinically significant infection requiring treatment with antibiotics, antiviral or additional corticosteroid medications finalised \< 2 weeks before Visit 1. * A helminth parasitic infection diagnosed within 6 months prior to Visit 1 that has not been treated with, or has failed to respond to, standard of care therapy. * Current smokers or participants with smoking history ≥ 10 pack-years and participants using vaping products, including electronic cigarettes. * History of chronic alcohol or drug abuse within 12 months prior to Visit 1. * Tuberculosis requiring treatment within the 12 months prior to Visit 1. * History of known immunodeficiency disorder including a positive HIV test at Visit 1. * Major surgery within 8 weeks prior to Visit 1 or planned surgical procedures requiring general anaesthesia or inpatient status for \> 1 day during the conduct of the study. * Coexistent inflammatory conditions for which long-term OCS doses are part of their maintenance treatment. * Receipt of any marketed or investigational biologic agent within 4 months or 5 half-lives (whichever is longer) prior to Visit 1 or receipt of any investigational nonbiologic agent within 30 days or 5 half-lives (whichever is longest) prior to Visit 1. Participants enrolled in current or previous tezepelumab studies will not be included. * Concurrent enrolment in another clinical study involving an IP. * Treatment with systemic immunosuppressive/immunomodulating drugs, except for OCS used in the treatment of asthma/asthma exacerbations, within the last 12 weeks or 5 half-lives (whichever is longer) prior to Visit 1. * History of anaphylaxis or documented immune complex disease (Type III hypersensitivity reactions) following any biologic therapy. * Positive hepatitis B surface antigen, or hepatitis C virus antibody serology at screening, or a positive medical history for hepatitis B or C. * Pregnant, breastfeeding, or lactating women. Other exclusion criteria per protocol apply.

Locations (77)

Outcomes

Primary Outcomes

Proportion of the Participants Who Discontinued OCS Without Loss of Asthma Control at Week 28 and Week 52

The proportion (expressed as a percentage) of participants who discontinued OCS without loss of asthma control is presented. Loss of asthma control was defined as asthma worsening or exacerbation. Asthma worsening was defined by an increase of Asthma Control Questionnaire 6 (ACQ-6) score ≥0.5 from baseline. Asthma exacerbation was defined by worsening of asthma symptoms that led to temporary bolus/burst of systemic corticosteroids (SCS; or a temporary increase in stable OCS background dose) for at least 3 consecutive days (a single depo-injectable dose of corticosteroids being considered equivalent to a 3-day bolus/burst of SCS), and/or an emergency room (ER) or urgent care visit requiring SCS, and/or inpatient hospitalisation, both due to asthma.

Time frame: Week 28 and Week 52

Proportion of the Participants Who Reduced Daily Prescribed Maintenance OCS Dose to ≤5 mg/Day Without Loss of Asthma Control at Week 28 and Week 52

The proportion (expressed as a percentage) of the participants who reduced daily prescribed maintenance OCS dose to ≤5 mg/day without loss of asthma control at Week 28 and Week 52 is presented.

Time frame: Week 28 and Week 52

Secondary Outcomes

Annual Asthma Exacerbation Rate (AAER) Over Week 28 and Over Week 52

The AAER over Week 28 and over Week 52 is presented. The AAER was calculated as the total number of asthma exacerbations over the period (Week 28/52) divided by the total time at risk for the period (Week 28 or Week 52).

Time frame: Week 28 and Week 52

Rate of Asthma Exacerbation Associated With Hospitalisation or ER Visit Over 28 Weeks and Over 52 Weeks

The AAER for exacerbations associated with hospitalisation or ER visit over 28 weeks and over 52 weeks is presented. The AAER was calculated as the total number of asthma exacerbations over the period (Week 28/52) divided by the total time at risk for the period (Week 28 or Week 52).

Data from ClinicalTrials.gov

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Research Site

Newport Beach, California, United States

Research Site

Newark, Delaware, United States

Research Site

Loxahatchee Groves, Florida, United States

Research Site

Ann Arbor, Michigan, United States

Research Site

Toms River, New Jersey, United States

Research Site

The Bronx, New York, United States

Research Site

DuBois, Pennsylvania, United States

Research Site

Buenos Aires, Argentina

Research Site

CABA, Argentina

Research Site

CABA, Argentina

...and 67 more locations

Time frame: Week 28 and Week 52

Rate of Asthma Exacerbation Associated With Hospitalisation Over 28 Weeks and Over 52 Weeks

The AAER for exacerbations associated with hospitalisation over 28 weeks and over 52 weeks are presented. The AAER was calculated as the total number of asthma exacerbations over the period (Week 28/52) divided by the total time at risk for the period (Week 28 or Week 52).

Time frame: Week 28 and Week 52

Proportion of the Participants Who Did Not Experience an Exacerbation Over 28 Weeks and Over 52 Weeks

The proportion (expressed as a percentage) of participants who completed 28 or 52 weeks of treatment and did not experience an exacerbation over 28 weeks and over 52 weeks is presented.

Time frame: Week 28 and Week 52

Proportion of the Participants Who Did Not Experience an Exacerbation Associated With Hospitalisation or ER Visit Over 28 Weeks and Over 52 Weeks

The proportion (expressed as a percentage) of participants who completed 28 or 52 weeks of treatment and did not experience an exacerbation associated with hospitalisation or ER visit over 28 weeks and over 52 weeks is presented.

Time frame: Week 28 and Week 52

Proportion of the Participants Who Did Not Experience an Exacerbation Associated With Hospitalisation Over 28 Weeks and Over 52 Weeks

The proportion (expressed as a percentage) of participants who completed 28 or 52 weeks of treatment and did not experience an exacerbation associated with hospitalisation over 28 weeks and over 52 weeks is presented.

Time frame: Week 28 and Week 52

Proportion of the Participants With ≥50% Reduction From Baseline in Daily Maintenance OCS Dose at Week 28 and Week 52

The proportion (expressed as a percentage) of participants with ≥50% reduction from baseline in daily maintenance OCS dose at Week 28 and Week 52 is presented. The baseline OCS dose is the prescribed OCS dose prior to first dose of investigational product (IP). The final daily OCS dose was defined as the last dose reported by participants with asthma stability verified (no change in OCS dose for at least 2 consecutive weeks).

Time frame: Week 28 and Week 52

Categorised Percent Reduction From Baseline in the Daily Maintenance OCS Dose at Week 28 and Week 52

The categorised percent reduction from baseline in the daily maintenance OCS dose (categories: ≥90% to ≤100% reduction, ≥75% to \<90% reduction, ≥50% to \<75% reduction, \>0% to \<50% reduction, no change or any increase) at Week 28 and Week 52 is presented. The baseline OCS dose is the prescribed OCS dose prior to first dose of IP. The final daily OCS dose was defined as the last dose reported by participants with asthma stability verified (no change in OCS dose for at least 2 consecutive weeks).

Time frame: Week 28 and Week 52

Absolute Change From Baseline in Daily Maintenance OCS Dose at Week 28 and Week 52

The absolute change from baseline in daily maintenance OCS dose at Week 28 and Week 52 is presented. The baseline OCS dose is the prescribed OCS dose prior to first dose of IP. The final daily OCS dose was defined as the last dose reported by participants with asthma stability verified (no change in OCS dose for at least 2 consecutive weeks).

Time frame: Week 28 and Week 52

Percent Change From Baseline in Daily Maintenance OCS Dose at Week 28 and Week 52

The percent change from baseline in daily maintenance OCS dose at Week 28 and Week 52 is presented. The baseline OCS dose is the prescribed OCS dose prior to first dose of IP. The final daily OCS dose was defined as the last dose reported by participants with asthma stability verified (no change in OCS dose for at least 2 consecutive weeks).

Time frame: Week 28 and Week 52

Change From Baseline in Post-bronchodilator FEV1 at Week 28 and Week 52

The change from baseline in post-bronchodilator FEV1 at Week 28 and Week 52 is presented. Baseline was defined as the last measurement at or prior first dose of IP. FEV1 = forced expiratory volume in 1 second

Time frame: Week 28 and Week 52

Change From Baseline in ACQ-6 at Week 28 and Week 52

The Asthma Control Questionnaire 6 (ACQ-6) is a 6-item questionnaire which includes the following questions: 1) Awakening at night by symptoms, 2) Limitations of normal daily activities, 3) Waking in the morning with symptoms, 4) Dyspnoea, 5) Wheeze, and 6) Daily rescue medication. Questions were scored from 0 (totally controlled) to 6 (severely uncontrolled) and the ACQ-6 score was computed as the unweighted mean of the responses to the 6 questions. Higher scores indicate poorer outcomes. The change from baseline in ACQ-6 at Week 28 and Week 52 is presented.

Time frame: Week 28 and Week 52

Change From Baseline in Standardised AQLQ(s)+12 Total Score at Week 28 and Week 52

The Asthma Quality of Life Questionnaire for 12 Years and Older (AQLQ\[S\]+12) is a questionnaire that measures the health-related quality of life experienced by asthma participants. Questions were scored from 7 (no impairment) to 1 (severe impairment). The overall score is calculated as the mean response to all questions. Higher scores indicate better outcomes. The change from baseline in standardised AQLQ(S)+12 total score at Week 28 and Week 52 is presented.

Time frame: Week 28 and Week 52

Change From Baseline in SGRQ Total Score at Week 28 and Week 52

The St. George's Respiratory Questionnaire (SGRQ) is a 50-item instrument developed to measure the health status of participants with airway obstruction diseases. The total score indicates the impact of disease on overall health status. The total score ranges for the SGRQ are 0-100, with higher scores indicating worse health status. The change from baseline in SGRQ total score at Week 28 and Week 52 is presented.

Time frame: Week 28 and Week 52