Efficacy and Safety of Tezepelumab in Reducing Oral Corticosteroid Use in Adults with Oral Corticosteroid-Dependent Asthma: A Randomized, Double-Blind, Placebo-Controlled Study
- Trial ID
- 2023-504648-33-00
- Protocol
- SUNRISE
- Sponsor
- AstraZeneca AB
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the effect of **tezepelumab** compared with placebo in reducing the prescribed oral corticosteroid (OCS) maintenance dose in participants with oral corticosteroid dependent asthma. This is clinically relevant as it aims to decrease the reliance on OCS, which are associated with significant side effects, thereby potentially improving patient outcomes and quality of life.
Secondary objectives include:
- Evaluating the effect of tezepelumab compared with placebo on pre-bronchodilator lung function in participants with asthma requiring chronic treatment with maintenance OCS in addition to high dose inhaled corticosteroids (ICS) plus long-acting beta-agonists (LABA).
- Assessing the effect of tezepelumab compared with placebo on the daily dose of maintenance OCS.
- Evaluating the effect of tezepelumab compared with placebo on asthma exacerbations.
- Assessing the effect of tezepelumab compared with placebo on asthma control and other asthma control metrics.
- Evaluating the effect of tezepelumab compared with placebo on asthma-related quality of life.
- Assessing the effect of tezepelumab on biomarkers.
- Evaluating the pharmacokinetics (PK) of tezepelumab.
- Evaluating the immunogenicity of tezepelumab.
Participants
The clinical trial involves a total of **329 participants** diagnosed with **Oral Corticosteroid Dependent Asthma**. The study population comprises both male and female subjects, aged between 18 to 80 years. Participants were selected based on their history of asthma, requiring chronic treatment with maintenance oral corticosteroids (OCS) in addition to high-dose inhaled corticosteroids (ICS) plus long-acting beta-agonists (LABA). All participants have a documented physician-diagnosed asthma for at least 12 months prior to the study and have been on a stable dose of OCS for at least one month before the trial. The trial includes individuals with a history of at least one asthma exacerbation event within 24 months prior to the study. Participants are required to have a body weight of at least 40 kg and demonstrate compliance with asthma controller medications and daily diary completion. The study population includes individuals who are capable of providing informed consent and are not restricted by significant lifestyle considerations such as diet or physical activity. The trial does not specifically exclude any vulnerable populations, and both genders are equally represented.
Plans and Procedures
The clinical trial is designed as a **randomized**, **double-blind**, parallel-group, placebo-controlled study to evaluate the efficacy and safety of **tezepelumab** in reducing oral corticosteroid use in adults with oral corticosteroid-dependent asthma. The trial is set to last for 28 weeks, with the primary objective being to assess the effect of tezepelumab compared to placebo in reducing the prescribed oral corticosteroid maintenance dose while maintaining asthma control. Participants will be randomly assigned to receive either tezepelumab or a placebo, both administered via subcutaneous injection using a pre-filled syringe.
The study will involve several key visits, starting with an inclusion (screening) visit to confirm eligibility based on criteria such as age, asthma history, and medication compliance. Participants must be between 18 and 80 years old, have a documented history of asthma, and meet specific medication compliance requirements. Following the screening, participants will undergo a randomization visit where they will be assigned to their respective treatment groups. Subsequent follow-up visits will occur at regular intervals to monitor safety, efficacy, and compliance with the study protocol. The end-of-study visit will conclude the trial, assessing the final outcomes and any changes in the participants' condition.
Participant involvement is expected to last the full 28 weeks, with conditions for early termination including non-compliance with study medication or procedures, adverse events, or withdrawal of consent. The primary endpoint is the categorized percent reduction from baseline in the daily maintenance oral corticosteroid dose at week 28. Secondary endpoints include changes in pre-bronchodilator forced expiratory volume, asthma exacerbation rates, and quality of life measures. The trial will also monitor tezepelumab serum concentrations and the incidence of anti-drug antibodies at specified intervals. The study aims to provide comprehensive data on the potential benefits of tezepelumab in managing oral corticosteroid-dependent asthma.
Treatment
The clinical trial involves the administration of **Tezepelumab**, marketed under the name Tezspire, which is a **solution for injection** in a pre-filled syringe. The active substance, tezepelumab, is a protein-based therapeutic agent. The pharmaceutical form is a solution for injection, and it is administered via **subcutaneous injection**. The dosage is 210 mg, with a maximum daily and total dose of 210 mg. The treatment period is set for 28 days. The product is provided by AstraZeneca AB and is not a pediatric formulation. The administration device is an accessorized prefilled syringe (APFS), which does not have a CE mark. Compliance with the dosing schedule is monitored throughout the trial.
The study also includes a **placebo** control, which is a tezepelumab placebo product provided in an accessorized prefilled syringe (APFS). The placebo is designed to match the experimental medication in appearance and administration method but does not contain the active substance. The placebo is used to maintain the double-blind nature of the trial, ensuring that neither the participants nor the investigators know who is receiving the active treatment or the placebo. This control is crucial for evaluating the efficacy and safety of tezepelumab in reducing oral corticosteroid use in adults with oral corticosteroid-dependent asthma.
Efficacy
Efficacy in this clinical trial will be assessed through a series of primary and secondary endpoints. The primary endpoint is the categorised percent reduction from baseline in the daily maintenance oral corticosteroid (OCS) dose at Week 28 while maintaining asthma control. The categories for percent change from baseline in daily OCS dose are defined as: 1. ≥ 90% to ≤ 100% reduction, 2. ≥ 75% to < 90% reduction, 3. ≥ 50% to < 75% reduction, 4. > 0% to < 50% reduction, and 5. no change or any increase.
Secondary endpoints include several measures: change from baseline in pre-bronchodilator forced expiratory volume in 1 second (**pre-BD FEV1**) at Week 28, proportion of participants with 100% reduction from baseline in daily maintenance OCS dose at Week 28, proportion of participants with daily maintenance OCS dose ≤ 5 mg at Week 28, and proportion of participants with ≥ 50% reduction from baseline in daily maintenance OCS dose at Week 28. Additionally, the annualised asthma exacerbation rate (AAER) over 28 weeks, time to first asthma exacerbation, and changes from baseline in the Asthma Control Questionnaire 6 (ACQ-6) score, weekly mean home peak expiratory flow (PEF), Standardized Asthma Quality of Life Questionnaire for 12 years and older (AQLQ(s)+12) total score, and St George's Respiratory Questionnaire (SGRQ) score at Week 28 will be evaluated. Biomarker assessments include changes from baseline in fractional exhaled nitric oxide (FeNO), peripheral blood eosinophils, and total serum immunoglobulin E (IgE) at Week 28. Pharmacokinetic and immunogenicity assessments will include tezepelumab serum trough concentrations at Weeks 0, 12, and 28, and the incidence of anti-drug antibodies (ADAs) at Weeks 0, 12, 28, and 40.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Age- Participant must be 18 to 80 years of age inclusive, at the time of signing the informed consent form
- Documented physician-diagnosed asthma for at least 12 months prior to Visit 1.
- Participants must have received a physician-prescribed medium- or high-dose ICS for at least 12 months prior to Visit 1.
- Participants must have received physician prescribed LABA and high dose ICS for at least 3 months prior to Visit 1. The ICS and LABA can be parts of a combination product or given by separate inhalers.
- Additional maintenance asthma controller medications are allowed according to standard practice of care ie, leukotriene receptor antagonists (LTRAs), theophylline, long-acting muscarinic antagonists (LAMAs), and chromones. The use of these medications must be documented for at least 3 months prior to Visit 1.
- Participants must have received OCS for the treatment of asthma for at least 6 months prior to Visit 1 and on a stable dose of between ≥ 7.5 to ≤ 30 mg (prednisone or prednisolone) daily or daily equivalent for at least one month prior to Visit 1.
- Morning pre-BD FEV1 must be < 80% predicted normal at Visit 1 or Visit 2.
- Evidence of asthma as documented by either: -Post-BD (albuterol/salbutamol) responsiveness test result: FEV1 ≥ 12% and ≥ 200 mL (15-30 min after administration of 4 puffs of albuterol/salbutamol), documented either in the previous 60 months prior to or at Visit 1 or at Visit 2 or at Visit 3. -Airway hyperresponsiveness (methacholine: provocative concentration that causes a positive reaction [PC20] of < 8 mg/mL) documented in the 60 months prior to Visit 1
- Blood eosinophils at Visit 1 ≥150 cells/μL(≥0.15 x109/L or ≥0.15 x103/µl) or documented EOS ≥ 300 cells/μL (≥0.3 x109 /L or ≥0.3 x103/µl) within 12 months prior to Visit 1
- Participants must have a history of at least one asthma exacerbation event within 24 months prior to Visit 1
- Body weight ≥ 40 kg at Visit 1
- Sex: male or female
- All women of childbearing potential must have a negative serum pregnancy test results at Visit 1 and a negative urine pregnancy test at randomisation.
- Female participants of childbearing potential who are sexually active with a non-sterilised male partner must agree to use one highly effective method of birth control , from enrolment throughout the study and until at least 16 weeks after last dose of study intervention.
- Capable of giving signed informed consent
- Provision of signed and dated written Optional Genetic Research Information informed consent prior to collection of samples for optional genetic research that supports Genomic Initiative.
- Minimum 10 days compliance with both the morning and evening daily diary completion and morning PEF measurements during the 14 days prior to Visit 2
- Minimum 10 days compliance with OCS, ICS, LABA and other asthma controller medications as captured in the daily diary during the 14 days prior to Visit 2.
- Participant must have received the optimised OCS dose for at least 2 weeks prior to randomisation.
- Minimum 70% compliance with all asthma controller medication dosing including OCS, ICS/LABA at Visits 3-5 during the OCS optimisation phase.
- Minimum 70% compliance with the morning and evening daily diary completion and morning PEF measurements at Visits 3-5 during the OCS optimisation phase.
- . Minimum 10 days compliance with the morning and evening daily diary completion and morning PEF measurement during the 14 days prior to randomisation.
- Minimum 10 days compliance with OCS, ICS, LABA and other asthma controller medications as captured in the daily diary during the 14 days prior to randomisation.
- Acceptable inhaler, peak flow meter, and spirometry techniques as judged by the investigator.
Exclusion Criteria
- Any clinically important pulmonary disease other than asthma (eg, active lung infection, Chronic Obstructive Pulmonary Disease (COPD), bronchiectasis, pulmonary fibrosis)
- History of cancer
- Asthma exacerbation, requiring use of systemic corticosteroids or increase in the maintenance dose of OCS finalised within 30 days prior to Visit 1.
- Clinically significant infection, including upper or lower respiratory tract infection (URTI and LRTI, respectively), requiring treatment with systemic antibiotics or antiviral medications finalised < 2 weeks before Visit 1 or during the run-in period.
- Participants with evidence of active COVID-19 infection during run-in period and optimisation. Evaluation will be based on local standard of care as determined by current local guidelines.
- A helminth 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.
- A participant who is on short-acting beta agonists (SABA) maintenance treatment within 30 days prior to Visit 1.
- Current smokers or participants with smoking history ≥ 10 pack-years and participants using vaping products, including electronic cigarettes. Former smokers with a smoking history of < 10 pack-years and users of vaping or e-cigarette products must have stopped for at least 6 months prior to Visit 1 to be eligible.
- Receipt of the T2 cytokine inhibitor Suplatast tosilate within 15 days prior to Visit 1.
- Receipt of live attenuated vaccines 30 days prior to the date of randomisation and during the study including the follow-up period.
- COVID-19 vaccination within 28 days prior to randomisation.
- Chronic alcohol or drug abuse within 12 months prior to Visit 1.
- Participants who have been treated with bronchial thermoplasty within 36 months prior to Visit 1.
- Sensitivity to any component of the study intervention formulation or a history of drug or other allergy that, in the opinion of the investigator or medical monitor, contraindicates their participation.
- History of anaphylaxis or documented immune complex disease (Type III hypersensitivity reactions) following any biologic therapy.
- Concurrent enrolment in another IP-related interventional clinical trial
- Participant randomised in other ongoing or previous tezepelumab studies.
- Involvement in the planning and/or conduct of the study (applies to AstraZeneca staff and/or site staff), or participants employed by or relatives of the employees of the site or sponsor.
- Any clinically meaningful abnormal findings in physical examination, vital signs, electrocardiogram (ECG), haematology, clinical chemistry, or urinalysis during the run-in period, which in the opinion of the investigator, may put the participant at risk because of his/her participation in the study, or may influence the results of the study, or the participant's ability to complete entire duration of the study
- Tuberculosis requiring treatment within the 12 months prior to Visit 1.
- A positive human immunodeficiency virus (HIV) test at Visit 1 or participant taking antiretroviral medications or history of any known immunodeficiency disorder, as determined by medical history and/or participant's verbal report.
- Major surgery within 8 weeks prior to Visit 1 or planned surgical procedures requiring general anaesthesia or hospitalisation for > 1 day during the conduct of the study.
- 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 non-biologic agent within 30 days or 5 half-lives (whichever is longer) prior to Visit 1.
- Treatment with the following medications within the last 12 weeks or 5 half-lives (whichever is longer) prior to Visit 1: systemic immunosuppressive/immunomodulating drugs (eg, methotrexate, cyclosporine, oral/parenteral/intra-articular corticosteroids for other use than treatment of asthma)
- Receipt of immunoglobulin or blood products within 30 days prior to Visit 1.
- Any disorder, including, but not limited to, cardiovascular, gastrointestinal, hepatic, renal, neurological, musculoskeletal, infectious, endocrine, metabolic, haematological, psychiatric, or major physical impairment that is not stable in the opinion of the investigator and could: (a) Affect the safety of the participant throughout the study (b) Influence the findings of the study or the interpretation (c) Impede the participant's ability to complete the entire duration of study
- Evidence of active liver disease, including jaundice or aspartate transaminase, alanine transaminase, or alkaline phosphatase beyond twice the upper limit of normal (ULN), at Visit 1.
- Positive hepatitis B surface antigen, or hepatitis C virus antibody serology at Visit 1, or a positive medical history for hepatitis B or C. Participants with a history of hepatitis B vaccination without a history of hepatitis B are allowed to participate.
- Women who are currently pregnant (confirmed with positive pregnancy test) or breastfeeding or lactating.
- Unwillingness or inability to follow the study procedures, or restrictions, in the opinion of the investigator.
- Previous allogeneic bone marrow transplant.
- Non-leukocyte depleted whole blood transfusion within 120 days of genetic sample collection.
- During the optimisation period, asthma control reached at an OCS dose of < 7.5 mg or > 30 mg and/or 3 consecutive dose reductions after which asthma control was still obtained.
- Evidence of clinically significant infection (including COVID-19) or participant receiving treatment with systemic antibiotics or antiviral medications.
- Despite screening of the participant, enrolment/randomisation is stopped at the study level.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Czechia | Not Recruiting | 04 Aug 2023 | 20 |
 Poland | Not Recruiting | 04 Aug 2023 | 56 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Tezspire 210 mg solution for injection in pre-filled syringe | Test | SOLUTION FOR INJECTION IN PRE-FILLED SYRINGE (INJECTION) | SUBCUTANEOUS INJECTION | 210 | 28 | PRD9947970 |
Tezepelumab placebo product in an accessorized prefilled syringeAPFS | Placebo | N/A | — | — | — | N/A |