Clinical trial NCT05398263: Tezepelumab Efficacy and Safety in Reducing Oral Corticosteroid Use in Adults With Oral Corticosteroid Dependent Asthma
Official title: A Randomised, Double-Blind, Parallel-Group, Placebo-Controlled 28-week Phase 3 Efficacy and Safety Study of Tezepelumab in Reducing Oral Corticosteroid Use in Adults With Oral Corticosteroid Dependent Asthma (SUNRISE)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Asthma
Keywords: Asthma
Severe Asthma
Oral Corticosteroid Dependent Asthma
Tezepelumab
Phase 3 Study
Reducing Oral Corticosteroid
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: Amgen
First posted: 2022-05-31
Enrollment: 125
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Subjects will be randomized in a 2:1 ratio to either tezepelumab or matching placebo both administered subcutaneously.
Primary purpose: TREATMENT

Brief summary: A Randomised, Double-Blind, Parallel-Group, Placebo-Controlled 28-week Phase 3 Efficacy and Safety Study of Tezepelumab in Reducing Oral Corticosteroid Use in Adults with Oral Corticosteroid Dependent Asthma

Detailed description: This is a multicentre, randomised, double-blind, placebo controlled, parallel group study designed to evaluate the efficacy and safety of tezepelumab in reducing oral corticosteroid use in adults with oral corticosteroid dependent asthma treated with maintenance OCS in combination with high dose inhaled corticosteroids (ICS) and long-acting β2 agonists (LABA), with or without other asthma controller therapies. Approximately 207 subjects will be randomized globally. Subjects will receive tezepelumab, or placebo, administered via subcutaneous injection using the accessorized pre-filled syringe (APFS), over a 28-week treatment period. The study also includes a post-treatment follow-up period of 12 weeks.

Eligibility criteria: Main inclusion criteria:

1. Participant must be 18 to 80 years of age.
2. Documented physician-diagnosed asthma for at least 12 months prior to Visit 1.
3. Participants must have received a physician-prescribed medium- or high-dose ICS for at least 12 months prior to Visit 1.
4. Participants must have received physician prescribed LABA and high dose ICS for at least 3 months prior to Visit 1.
5. Additional maintenance asthma controller medications are allowed. The use of these medications must be documented for at least 3 months prior to Visit 1.
6. 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 1 month prior to Visit 1.
7. Morning pre- bronchodilator (BD) FEV1 must be \< 80% predicted normal at Visit 1 or Visit 2.
8. Evidence of asthma as documented by either:

   a)Post-BD responsiveness test result: FEV1 ≥12% and ≥200 mL documented either in the previous 60 months prior to or at Visit 1 or at Visit 2 or at Visit 3; OR b)Airway hyperresponsiveness (methacholine: provocative concentration that causes a positive reaction \[PC20\] of \<8 mg/mL) documented in the 60 months prior to Visit 1.
9. Blood eosinophils at Visit 1 ≥150 cells/μL or documented EOS ≥300 cells/μL within 12 months prior to Visit 1.
10. Participants must have a history of at least 1 asthma exacerbation event within 24 months prior to Visit 1.
11. Participants must have received the optimised OCS dose for at least 2 weeks prior to randomisation.

Other inclusion criteria per protocol apply.

Main exclusion criteria

1. Any clinically important pulmonary disease other than asthma.
2. Any disorder 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.
3. History of cancer: a. Participants who have had basal cell carcinoma, localised squamous cell carcinoma of the skin or in situ carcinoma of the cervix are eligible to participate in the study provided that curative therapy was completed at least 12 months prior to Visit 1; b. Participants who have had other malignancies are eligible provided that curative therapy was completed at least 5 years prior to Visit 1.
4. Asthma exacerbation, requiring use of systemic corticosteroids or increase in the maintenance dose of OCS finalized within 30 days prior to Visit 1.
5. Clinically significant infection requiring treatment with systemic antibiotics or antiviral medications finalized \< 2 weeks before Visit 1 or during the run-in period.
6. Participants with evidence of active COVID-19 infection during run-in period and optimisation.
7. 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.
8. A participant who is on SABA maintenance treatment within 30 days prior to Visit 1.
9. 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.
10. 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.
11. COVID-19 vaccination within 28 days prior to randomisation.
12. Tuberculosis requiring treatment within the 12 months prior to Visit 1.
13. 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.

Other exclusion criteria per protocol apply.

Primary outcomes:
measure: Categorised percent reduction from baseline in the daily maintenance OCS dose at Week 28 whilst maintaining asthma control.
timeFrame: Baseline to Week 28
Secondary outcomes:
measure: Change from baseline in pre-bronchodilator (pre-BD) forced expiratory volume in 1 second (FEV1) at Week 28
timeFrame: Baseline to Week 28
measure: Proportion of subjects with 100% reduction from baseline in daily OCS dose at Week 28
timeFrame: Baseline to Week 28
measure: Proportion of subjects with daily OCS dose ≤5 mg at Week 28
timeFrame: Week 28
measure: Proportion of subjects with ≥50% reduction from baseline in daily OCS dose at Week 28
timeFrame: Baseline to Week 28
measure: Annualised asthma exacerbation rate (AAER) over 28 weeks
timeFrame: Baseline to Week 28
measure: Time to first asthma exacerbation
timeFrame: Baseline to Week 28
measure: Change from baseline in Asthma Control Questionnaire 6 (ACQ-6) score at Week 28
timeFrame: Baseline to Week 28
measure: Change from baseline in weekly mean home peak expiratory flow (PEF) (morning and evening) at Week 28
timeFrame: Baseline to Week 28
measure: Change from baseline in Standardized Asthma Quality of Life Questionnaire for 12 years and older (AQLQ(s)+12) total score at Week 28
timeFrame: Baseline to Week 28
measure: Change From Baseline in St George's Respiratory Questionnaire (SGRQ) Score at Week 28
timeFrame: Baseline to Week 28
measure: Change from baseline in fractional exhaled nitric oxide (FeNO) at Week 28
timeFrame: Baseline to Week 28
measure: Change from baseline in peripheral blood eosinophils at Week 28
timeFrame: Baseline to Week 28
measure: Change from baseline in total serum immunoglobulin E (IgE) at Week 28
timeFrame: Baseline to Week 28
measure: PK: Serum trough concentrations at Week 0, 12 and 28
timeFrame: Baseline, Week 12 and Week 28
measure: Immunogenicity: Incidence of anti-drug antibodies (ADA) at Week 0, 12, 28, and 40
timeFrame: Baseline to Week 40
Other outcomes:
Locations:
city: Newport Beach
country: United States
facility: Research Site
state: California
city: Denver
country: United States
facility: Research Site
state: Colorado
city: Newark
country: United States
facility: Research Site
state: Delaware
city: Hialeah
country: United States
facility: Research Site
state: Florida
city: Miami Lakes
country: United States
facility: Research Site
state: Florida
city: Lincoln
country: United States
facility: Research Site
state: Nebraska
city: Bronx
country: United States
facility: Research Site
state: New York
city: El Paso
country: United States
facility: Research Site
state: Texas
city: Kingwood
country: United States
facility: Research Site
state: Texas
city: Botucatu
country: Brazil
facility: Research Site
city: Curitiba
country: Brazil
facility: Research Site
city: Porto Alegre
country: Brazil
facility: Research Site
city: Porto Alegre
country: Brazil
facility: Research Site
city: Salvador
country: Brazil
facility: Research Site
city: Sao Bernardo do Campo
country: Brazil
facility: Research Site
city: Sorocaba
country: Brazil
facility: Research Site
city: São Paulo
country: Brazil
facility: Research Site
city: Ajax
country: Canada
facility: Research Site
state: Ontario
city: Quebec
country: Canada
facility: Research Site
city: Curico
country: Chile
facility: Research Site
city: Santiago
country: Chile
facility: Research Site
city: Santiago
country: Chile
facility: Research Site
city: Santiago
country: Chile
facility: Research Site
city: Santiago
country: Chile
facility: Research Site
city: Santiago
country: Chile
facility: Research Site
city: Santiago
country: Chile
facility: Research Site
city: Santiago
country: Chile
facility: Research Site
city: Brno
country: Czechia
facility: Research Site
city: Hradec Kralove
country: Czechia
facility: Research Site
city: Jindrichuv Hradec
country: Czechia
facility: Research Site
city: Moravsky Krumlov
country: Czechia
facility: Research Site
city: Olomouc
country: Czechia
facility: Research Site
city: Ostrava
country: Czechia
facility: Research Site
city: Ajmer
country: India
facility: Research Site
city: Kanpur
country: India
facility: Research Site
city: Vadodara
country: India
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Suwon-si
country: Korea, Republic of
facility: Research Site
city: Guadalajara
country: Mexico
facility: Research Site
city: Guadalajara
country: Mexico
facility: Research Site
city: Guadalajara
country: Mexico
facility: Research Site
city: Mexico City
country: Mexico
facility: Research Site
city: Monterrey
country: Mexico
facility: Research Site
city: San Luis Potosí
country: Mexico
facility: Research Site
city: Veracruz
country: Mexico
facility: Research Site
city: Lima
country: Peru
facility: Research Site
city: Białystok
country: Poland
facility: Research Site
city: Bychawa
country: Poland
facility: Research Site
city: Bydgoszcz
country: Poland
facility: Research Site
city: Chęciny
country: Poland
facility: Research Site
city: Grudziądz
country: Poland
facility: Research Site
city: Ostrowiec Świętokrzyski
country: Poland
facility: Research Site
city: Poznań
country: Poland
facility: Research Site
city: Rzeszów
country: Poland
facility: Research Site
city: Sosnowiec
country: Poland
facility: Research Site
city: Bang Kra So
country: Thailand
facility: Research Site
city: Bangkok
country: Thailand
facility: Research Site
city: Hat Yai
country: Thailand
facility: Research Site
city: Hatyai
country: Thailand
facility: Research Site
city: Ankara
country: Turkey
facility: Research Site
city: Bursa
country: Turkey
facility: Research Site
city: Istambul
country: Turkey
facility: Research Site
city: Izmir
country: Turkey
facility: Research Site
Study officials:
References: