SUNRISE: Tezepelumab Efficacy and Safety in Reducing Oral Corticosteroid Use in Adults With Oral Corticosteroid Dependent Asthma

Sponsor

AstraZeneca (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05398263

Collaborator

Amgen (Industry)

207

Enrollment

Locations

Arms

36.7

Anticipated Duration (Months)

4.2

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

A Randomised, Double-Blind, Parallel-Group, Placebo-Controlled 40-week Phase 3 Efficacy and Safety Study of Tezepelumab in Reducing Oral Corticosteroid Use in Adults with Oral Corticosteroid Dependent Asthma

Condition or Disease	Intervention/Treatment	Phase
Asthma	Biological: Tezepelumab Other: Placebo	Phase 3

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

207 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Subjects will be randomized in a 2:1 ratio to either tezepelumab or matching placebo both administered subcutaneously.Subjects will be randomized in a 2:1 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 Randomised, Double-Blind, Parallel-Group, Placebo-Controlled 40-week Phase 3 Efficacy and Safety Study of Tezepelumab in Reducing Oral Corticosteroid Use in Adults With Oral Corticosteroid Dependent Asthma (SUNRISE)

Anticipated Study Start Date :

Jun 9, 2022

Anticipated Primary Completion Date :

Apr 7, 2025

Anticipated Study Completion Date :

Jun 30, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Tezepelumab Tezepelumab subcutaneous injection, in an accessorised pre-filled syringe.	Biological: Tezepelumab Tezepelumab subcutaneous injection
Placebo Comparator: Placebo Placebo subcutaneous injection, in an accessorised pre-filled syringe.	Other: Placebo Placebo subcutaneous injection

Arm

Intervention/Treatment

Experimental: Tezepelumab

Tezepelumab subcutaneous injection, in an accessorised pre-filled syringe.

Biological: Tezepelumab

Tezepelumab subcutaneous injection

Placebo Comparator: Placebo

Placebo subcutaneous injection, in an accessorised pre-filled syringe.

Other: Placebo

Placebo subcutaneous injection

Outcome Measures

Primary Outcome Measures

Categorised percent reduction from baseline in the daily maintenance OCS dose at Week 28 whilst maintaining asthma control. [Baseline to Week 28]
Categorised percent reduction from baseline at Week 28. Percent change from baseline is defined as {final dose-baseline dose)/baseline dose}*100%, and the categories of percent change from baseline in daily OCS dose are defined as: ≥90% to ≤100% reduction, ≥75% to <90% reduction, ≥50% to <75% reduction, >0% to <50% reduction, and, no change or any increase.

Secondary Outcome Measures

Change from baseline in pre-bronchodilator (pre-BD) forced expiratory volume in 1 second (FEV1) at Week 28 [Baseline to Week 28]
Change from baseline in pre-BD FEV1 at Week 28. FEV1 is defined as the volume of air exhaled from the lungs in the first second of a forced expiration.
Proportion of subjects with 100% reduction from baseline in daily OCS dose at Week 28 [Baseline to Week 28]
Proportion of subjects with 100% reduction from baseline in daily OCS dose at Week 28. Percent change from baseline is defined as {(final dose-baseline dose)/baseline dose}*100%.
Proportion of subjects with daily OCS dose ≤5 mg at Week 28 [Week 28]
Proportion of subjects with daily OCS dose ≤5 mg at Week 28.
Proportion of subjects with ≥50% reduction from baseline in daily OCS dose at Week 28 [Baseline to Week 28]
Proportion of subjects with ≥50% reduction from baseline in daily OCS dose at Week 28. Percent change from baseline is defined as {(final dose-baseline dose)/baseline dose}*100%.
Annualised asthma exacerbation rate (AAER) over 28 weeks [Baseline to Week 28]
The annualized exacerbation rate is based on exacerbations reported by the investigator in the eCRF over 28 weeks.
Time to first asthma exacerbation [Baseline to Week 28]
Time to first asthma exacerbation.
Change from baseline in Asthma Control Questionnaire 6 (ACQ-6) score at Week 28 [Baseline to Week 28]
Change from baseline in ACQ-6 as compared to placebo at Week 28. 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.
Change from baseline in weekly mean home peak expiratory flow (PEF) (morning and evening) at Week 28 [Baseline to Week 28]
Change from baseline in weekly mean morning and evening peak expiratory flow (PEF) as compared to placebo at Week 28. 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.
Change from baseline in Standardized Asthma Quality of Life Questionnaire for 12 years and older (AQLQ(s)+12) total score at Week 28 [Baseline to Week 28]
Change from baseline in AQLQ(S)+12 as compared to placebo at Week 28. 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).
Change From Baseline in St George's Respiratory Questionnaire (SGRQ) Score at Week 28 [Baseline to Week 28]
Change from baseline in SGRQ as compared to placebo at Week 28. The questionnaire is divided into 2 parts: part 1 consists of 8 items pertaining to the severity of respiratory symptoms in the preceding 4 weeks; part 2 consists of 42 items related to the daily activity and psychosocial impacts of the individual's respiratory condition. The total score indicates the impact of disease on overall health status. This total score is expressed as a percentage of overall impairment, in which 100 represents the worst possible health status and 0 indicates the best possible health status.
Change from baseline in fractional exhaled nitric oxide (FeNO) at Week 28 [Baseline to Week 28]
Change from baseline in fractional exhaled nitric oxide (FeNO) at Week 28.
Change from baseline in peripheral blood eosinophils at Week 28 [Baseline to Week 28]
Change from baseline in blood eosinophil counts at Week 28.
Change from baseline in total serum immunoglobulin E (IgE) at Week 28 [Baseline to Week 28]
Change from baseline in total serum IgE at Week 28.
PK: Serum trough concentrations at Week 0, 12 and 28 [Baseline, Week 12 and Week 28]
Pharmacokinetics samples are collected at baseline and at Week 12 prior to study intervention administration, and at Week 28 (End of Treatment visit).
Immunogenicity: Incidence of anti-drug antibodies (ADA) at Week 0, 12, 28, and 40 [Baseline to Week 40]
Immunogenicity samples are collected at baseline and at Week 12 prior to study intervention administration, at Week 28 (End of Treatment visit) and at Week 40 (Follow-up visit). 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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Main inclusion criteria:

Participant must be 18 to 80 years of age.
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.
Additional maintenance asthma controller medications are allowed. 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 1 month prior to Visit 1.
Morning pre- bronchodilator (BD) FEV1 must be < 80% predicted normal at Visit 1 or Visit 2. a) Post-BD reversibility of 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.
Blood eosinophils at Visit 1 ≥150 cells/μL or documented EOS ≥300 cells/μL within 12 months prior to Visit 1.
Participants must have a history of at least 1 asthma exacerbation event within 24 months prior to Visit 1.
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

Any clinically important pulmonary disease other than asthma.
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.
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.
Asthma exacerbation, requiring use of systemic corticosteroids or increase in the maintenance dose of OCS finalized within 30 days prior to Visit 1.
Clinically significant infection requiring treatment with antibiotics or antiviral medications finalized < 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.
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 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 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 longest) prior to Visit 1.
COVID-19 vaccination within 7 days prior to randomisation.
Tuberculosis requiring treatment within the 12 months prior to Visit 1.
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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Denver	Colorado	United States	80206
2	Research Site	Newark	Delaware	United States	19713
3	Research Site	Bloomington	Indiana	United States	47408
4	Research Site	Hazelwood	Missouri	United States	63042
5	Research Site	Lincoln	Nebraska	United States	68510
6	Research Site	Knoxville	Tennessee	United States	37919
7	Research Site	El Paso	Texas	United States	79902
8	Research Site	Kingwood	Texas	United States	77339
9	Research Site	Rio de Janeiro		Brazil	22061-080
10	Research Site	Vancouver	British Columbia	Canada	V6Z 1Y6
11	Research Site	Ajax	Ontario	Canada	L1S 2J5
12	Research Site	Quebec		Canada	G1V4G5
13	Research Site	Santiago de Chile		Chile
14	Research Site	Santiago		Chile	7500010
15	Research Site	Santiago		Chile	7500692
16	Research Site	Santiago		Chile	7500698
17	Research Site	Santiago		Chile	7750495
18	Research Site	Santiago		Chile	8241479
19	Research Site	Valparaiso		Chile	2341131
20	Research Site	Brno		Czechia	625 00
21	Research Site	Hradec Kralove		Czechia	500 05
22	Research Site	Jindrichuv Hradec		Czechia	377 01
23	Research Site	Moravsky Krumlov		Czechia	67201
24	Research Site	Olomouc		Czechia	779 00
25	Research Site	Seoul		Korea, Republic of	03722
26	Research Site	Seoul		Korea, Republic of	05505
27	Research Site	Seoul		Korea, Republic of	07061
28	Research Site	Seoul		Korea, Republic of	143-729
29	Research Site	Suwon-si		Korea, Republic of	16499
30	Research Site	Guadalajara		Mexico	44100
31	Research Site	Guadalajara		Mexico	44130
32	Research Site	Guadalajara		Mexico	44200
33	Research Site	Mexico City		Mexico	0 3100
34	Research Site	Monterrey		Mexico	64460
35	Research Site	Puebla		Mexico	72190
36	Research Site	San Luis Potosí		Mexico	78250
37	Research Site	Veracruz		Mexico	91910
38	Research Site	Białystok		Poland	15-430
39	Research Site	Grudziądz		Poland	86-300
40	Research Site	Krakow		Poland	30-033
41	Research Site	Ostrowiec Świętokrzyski		Poland	27-400
42	Research Site	Poznań		Poland	61-578
43	Research Site	Rzeszów		Poland	35-205
44	Research Site	Sosnowiec		Poland	41-205
45	Research Site	Ankara		Turkey	06620
46	Research Site	Bursa		Turkey	16059
47	Research Site	Istanbul		Turkey	34098
48	Research Site	Izmir		Turkey	35040
49	Research Site	Izmir		Turkey	35110