COURSE: Tezepelumab COPD Exacerbation Study

Sponsor

AstraZeneca (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04039113

Collaborator

Amgen (Industry)

338

Enrollment

Locations

Arms

55.8

Anticipated Duration (Months)

3.4

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel Group, Phase 2a Study to Explore the Efficacy and Safety of Tezepelumab in Adults with Moderate to Very Severe Chronic Obstructive Pulmonary Disease (COPD)

Condition or Disease	Intervention/Treatment	Phase
Chronic Obstructive Pulmonary Disease (COPD)	Biological: Tezepelumab Other: Placebo	Phase 2

Detailed Description

This is a Phase 2a, multicenter, randomized, double-blind, placebo-controlled, parallel group study to evaluate the safety and efficacy of tezepelumab in adults with moderate to very severe chronic obstructive pulmonary disease (COPD) receiving triple inhaled maintenance therapy, and having had 2 or more documented COPD exacerbations in the 12 months prior to Visit 1. Approximately, 338 subjects will be randomized globally. Subjects will be stratified by region and prior number of exacerbations (2 vs. 3 or more). Subjects 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 Design

Study Type:

Interventional

Anticipated Enrollment :

338 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Subjects will be randomized in a 1:1 ratio to either tezepelumab or matching placebo both administered subcutaneously.Subjects will be randomized in a 1:1 ratio to either tezepelumab or matching placebo both administered subcutaneously.

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description:

Double-blinded

Primary Purpose:

Treatment

Official Title:

A Randomized, Double-blind, Placebo-controlled, Parallel Group, Multicenter Phase 2a Study to Explore the Efficacy and Safety of Tezepelumab in Patients With Moderate to Very Severe Chronic Obstructive Pulmonary Disease (COPD) (COURSE)

Actual Study Start Date :

Jul 30, 2019

Anticipated Primary Completion Date :

Dec 29, 2023

Anticipated Study Completion Date :

Mar 22, 2024

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Tezepelumab Tezepelumab, SC, Q4W	Biological: Tezepelumab Tezepelumab subcutaneous injection
Placebo Comparator: Matching Placebo Matching placebo, SC, Q4W	Other: Placebo Placebo subcutaneous injection

Arm

Intervention/Treatment

Active Comparator: Tezepelumab

Tezepelumab, SC, Q4W

Biological: Tezepelumab

Tezepelumab subcutaneous injection

Placebo Comparator: Matching Placebo

Matching placebo, SC, Q4W

Other: Placebo

Placebo subcutaneous injection

Outcome Measures

Primary Outcome Measures

Moderate or severe COPD exacerbation rate ratio (tezepelumab vs placebo) [Over 52 Weeks]
The exacerbation rate is based on exacerbations reported by the investigator over 52 weeks.

Secondary Outcome Measures

Time to first moderate or severe COPD exacerbation [By Week 52]
Time to first occurrence of moderate/severe exacerbation post randomization. Outcome measures: Hazard ratio
Proportion with at least one moderate/severe COPD exacerbation [Over 52 Weeks]
Proportion of subjects with at least one moderate/severe exacerbation reported by the Investigator over 52 weeks Outcome measure: Odds Ratio
Severe COPD exacerbation rate ratio (tezepelumab vs. placebo) [Over 52 Weeks]
The severe exacerbation rate is based on severe exacerbations reported by the Investigator over 52 weeks.
Change from baseline in pre-bronchodilator (pre-BD) forced expiratory volume in 1 second (FEV1) [Baseline, Week 52]
Difference in change from baseline in pre-BD forced expiratory volume in 1 second (FEV1) in tezepelumab arm as compared to placebo at Week 52. FEV1 is defined as the volume of air exhaled from the lungs in the first second of forced expiration.
Change in respiratory health status/health-related quality of life [Baseline, Week 52]
Proportion of subjects achieving a decrease of 4 units or more in the St. George's Respiratory Questionnaire (SGRQ) total score at Week 52, i.e. minimum clinically important difference (MCID). Outcome measure: odds ratio
Change from baseline in St. George's Respiratory Questionnaire (SGRQ) Total Score [Baseline, Week 52]
Difference (tezepelumab vs. placebo) in SGRQ from baseline at Week 52. SGRQ is a 50-item patient reported outcome questionnaire. The SGRQ total score is expressed as a percentage of overall impairment, in which 100% means the worst possible health status and 0% indicates the best possible health status. Likewise, the domain scores range from 0 to 100, with higher scores indicative of greater impairment. Decrease of 4 units is associated with a minimum clinically important difference (MCID).
Change from baseline in the COPD Assessment Test (CAT) Total Score [Baseline, Week 52]
Difference (tezepelumab vs. placebo) in COPD assessment tool (CAT) from baseline at Week 52. CAT is an 8-item patient reported outcome questionnaire developed to measure the impact of COPD on health status. The instrument uses semantic differential six-point response scales. A CAT total score is the sum of item responses. The score ranges from 0 to 40, with higher scores indicating greater COPD impact on health status.
Evaluate pharmacokinetics of tezepelumab [Weeks 0, 4, 12, 24, 36, 52, 64]
Serum trough concentration of tezepelumab
Evaluate immunogenicity of tezepelumab [Over 52 weeks]
Incidence of anti-drug antibodies (ADA)

Eligibility Criteria

Criteria

Ages Eligible for Study:

40 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

History of moderate to very severe physician-diagnosed COPD for at least 12 months prior to enrolment with a post-bronchodilator FEV1/FVC<0.70 and a post-bronchodilator FEV1 ≥20% and ≤80% of predicted normal value.
History of at least 2 documented moderate to severe COPD exacerbations within 2 to 52 weeks prior to enrollment.
CAT score of ≥15 at enrollment and on day of randomization.
Documented treatment with triple therapy for COPD (medium or high dose ICS/LABA/LAMA) throughout the year prior to enrollment. The dose of ICS should be stable for 3 months prior to enrollment.

Exclusion Criteria:

Clinically important pulmonary disease other than COPD, as judged by the Investigator (including current or historic asthma diagnosis).
Any disorder, including, but not limited to, cardiovascular, gastrointestinal, hepatic, renal, neurological, musculoskeletal, infectious (including risk factors for pneumonia), endocrine, metabolic, hematological, psychiatric, or major physical impairment that is not stable.
Major surgery within 8 weeks before enrollment.
History of clinically significant infection requiring antibiotics or antiviral medication within 14 days before enrollment.
Pregnant or breastfeeding.
The chest/lungs with pathology that precludes the patient's ability to complete the study
The patient has active COVID 19 infection during screening period.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Dothan	Alabama	United States	36303
2	Research Site	Huntington Beach	California	United States	92647
3	Research Site	Los Angeles	California	United States	90095
4	Research Site	Newport Beach	California	United States	92663
5	Research Site	Sacramento	California	United States	95817
6	Research Site	Upland	California	United States	91786
7	Research Site	Westminster	California	United States	92683
8	Research Site	New Haven	Connecticut	United States	06510
9	Research Site	Brandon	Florida	United States	33511
10	Research Site	Loxahatchee Groves	Florida	United States	33470
11	Research Site	Orlando	Florida	United States	32819
12	Research Site	Panama City	Florida	United States	32405
13	Research Site	Tampa	Florida	United States	33607
14	Research Site	Winter Park	Florida	United States	32789-4681
15	Research Site	Evanston	Illinois	United States	60201
16	Research Site	Buckley	Michigan	United States	49620
17	Research Site	Albuquerque	New Mexico	United States	87108
18	Research Site	Charlotte	North Carolina	United States	28277
19	Research Site	Mooresville	North Carolina	United States	28117
20	Research Site	New Bern	North Carolina	United States	28562
21	Research Site	Columbus	Ohio	United States	43215
22	Research Site	Edmond	Oklahoma	United States	73034
23	Research Site	Medford	Oregon	United States	97504
24	Research Site	Philadelphia	Pennsylvania	United States	19140
25	Research Site	Pittsburgh	Pennsylvania	United States	15213
26	Research Site	Mount Pleasant	South Carolina	United States	29464
27	Research Site	Rock Hill	South Carolina	United States	29732
28	Research Site	Rapid City	South Dakota	United States	57702
29	Research Site	McKinney	Texas	United States	75069
30	Research Site	Abingdon	Virginia	United States	24210
31	Research Site	Everett	Washington	United States	98208
32	Research Site	Calgary	Alberta	Canada	T2N 4Z6
33	Research Site	Sherwood Park	Alberta	Canada	T8L 0N2
34	Research Site	Vancouver	British Columbia	Canada	V5Z 1M9
35	Research Site	Truro	Nova Scotia	Canada	B2N 1L2
36	Research Site	Burlington	Ontario	Canada	L7N 3V2
37	Research Site	Hamilton	Ontario	Canada	L8N 3Z5
38	Research Site	Windsor	Ontario	Canada	N8X-5A6
39	Research Site	Montreal	Quebec	Canada	H1M 1B1
40	Research Site	St Charles Borromee	Quebec	Canada	J6E 2B4
41	Research Site	Trois-Rivières	Quebec	Canada	G8T 7A1
42	Research Site	Quebec		Canada	G1V 4G5
43	Research Site	Quebec		Canada	G3K 2P8
44	Research Site	Aarhus N		Denmark	8200
45	Research Site	Hvidovre		Denmark	2650
46	Research Site	København NV		Denmark	2400
47	Research Site	Odense C		Denmark	5000
48	Research Site	Roskilde		Denmark	4000
49	Research Site	Vejle		Denmark	7100
50	Research Site	Ålborg		Denmark	9000
51	Research Site	Amiens Cedex 1		France	80054
52	Research Site	Brest Cedex 2		France	29609
53	Research Site	Creteil		France	94010
54	Research Site	Grenoble Cedex		France	38043
55	Research Site	Lyon Cedex 04		France	69317
56	Research Site	Marseille		France	13015
57	Research Site	Montpellier		France	34090
58	Research Site	Nantes Cedex 1		France	44093
59	Research Site	Berlin		Germany	12203
60	Research Site	Frankfurt		Germany	60596
61	Research Site	Grosshansdorf		Germany	20927
62	Research Site	Lübeck		Germany	23552
63	Research Site	Mainz		Germany	55131
64	Research Site	Ashkelon		Israel	7830604
65	Research Site	Beer Sheva		Israel	84101
66	Research Site	Haifa		Israel	34362
67	Research Site	Jerusalem		Israel	91031
68	Research Site	Jerusalem		Israel	91120
69	Research Site	Kfar Saba		Israel	49281
70	Research Site	Rehovot		Israel	7661041
71	Research Site	Daegu		Korea, Republic of	42415
72	Research Site	Incheon		Korea, Republic of	21431
73	Research Site	Jeonju-si		Korea, Republic of	54907
74	Research Site	Seoul		Korea, Republic of	03312
75	Research Site	Seoul		Korea, Republic of	03722
76	Research Site	Seoul		Korea, Republic of	05030
77	Research Site	Seoul		Korea, Republic of	05505
78	Research Site	Seoul		Korea, Republic of	06591
79	Research Site	Seoul		Korea, Republic of	06973
80	Research Site	Uijeongbu-si		Korea, Republic of	11765
81	Research Site	Eindhoven		Netherlands	5623 EJ
82	Research Site	Heerlen		Netherlands	6419 PC
83	Research Site	Rotterdam		Netherlands	3045 PM
84	Research Site	Rotterdam		Netherlands	3083 AN
85	Research Site	Zutphen		Netherlands	7207 AE
86	Research Site	Alzira		Spain	46410
87	Research Site	Barcelona		Spain	08025
88	Research Site	Granada		Spain	18014
89	Research Site	Málaga		Spain	29010
90	Research Site	Mérida (Badajoz)		Spain	06800
91	Research Site	Bradford		United Kingdom	BND9 6RJ
92	Research Site	Chertsey		United Kingdom	KT16 0PZ
93	Research Site	Cottingham		United Kingdom	HU16 5JQ
94	Research Site	Glasgow		United Kingdom	G12 0YN
95	Research Site	London		United Kingdom	SW10 9NH
96	Research Site	Newcastle-upon-Tyne		United Kingdom	NE1 4LP
97	Research Site	Wakefield		United Kingdom	WF1 4DG
98	Research Site	Wythenshawe		United Kingdom	M23 9QZ