PROSPERO: Long-term Efficacy and Safety of Tozorakimab in Participants With Chronic Obstructive Pulmonary Disease With a History of Exacerbations.

• Sponsor: AstraZeneca (Industry)
• Overall Status: Not yet recruiting
• CT.gov ID: NCT05742802
• Collaborator: (none)
• Enrollment: 2,544
• Locations: 114
• Arms: 3
• Anticipated Duration (Months): 42.2
• Patients Per Site: 22.3
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

Subjects who completed either OBERON or TITANIA will be offered the opportunity to consent for this Multicentre, Double-blind, Randomised, Placebo controlled, Parallel Group, Phase 3, extension study to evaluate the safety and efficacy of Tozorakimab in adult participants with symptomatic COPD.

Condition or Disease	Intervention/Treatment	Phase
Chronic Obstructive Pulmonary Disease (COPD)	Combination Product: Tozorakimab; Combination Product: Tozorakimab; Combination Product: Placebo	Phase 3

Detailed Description

Participants who have completed the study treatment period and have not been prematurely discontinued from IP in one of the predecessor studies, OBERON or TITANIA, will be offered the opportunity to consent for this Multicentre, Double-blind, Randomised, Placebo-controlled, Parallel Group, Phase 3 extension study to evaluate the efficacy and safety of Tozorakimab versus placebo in adult (40 years and older) participants with symptomatic COPD and with a history of exacerbations

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 2544 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase III, Multicentre, Randomised, Double-blind, Chronic-dosing, Parallel-group, Placebo-controlled Extension Study to Evaluate the Long-term Efficacy and Safety of Tozorakimab (MEDI3506) in Participants With Chronic Obstructive Pulmonary Disease (COPD) With a History of Exacerbations.
• Anticipated Study Start Date: Feb 20, 2023
• Anticipated Primary Completion Date: Jun 30, 2025
• Anticipated Study Completion Date: Aug 27, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Tozorakimab Dose 1 Injection subcutaneously Tozorakimab or placebo via pre-filled syringe.	Combination Product: Tozorakimab; Participants previously randomised to Tozorakimab in one of the predecessor studies will be assigned to the same Tozorakimab dose and regimen in the PROSPERO study.
Experimental: Tozorakimab Dose 2 Injection subcutaneously Tozorakimab via pre-filled syringe.	Combination Product: Tozorakimab; Participants previously randomised to Tozorakimab in one of the predecessor studies will be assigned to the same Tozorakimab dose and regimen in the PROSPERO study.
Placebo Comparator: Placebo Injection subcutaneously with equivalent volume to Tozorakimab via pre-filled syringe.	Combination Product: Placebo; Participants previously randomised to placebo in one of the predecessor studies will be reassigned to one of the active doses of Tozorakimab or placebo in a 1:1:2 ratio.

Outcome Measures

Primary Outcome Measures

1. Time to first severe COPD exacerbation in former smokers. [104 weeks total (52 weeks in this study)]

   The primary efficacy endpoint is the time to first severe COPD exacerbation over the treatment period incorporating both the predecessor studies and PROSPERO. The primary endpoint will be assessed first in the Primary Population of former smokers, followed by the Overall Population of current and former smokers.

Secondary Outcome Measures

1. Time to first severe COPD exacerbation. [104 weeks total (52 weeks in this study)]

   To be analysed as a key secondary endpoint in the Overall Population of current and former smokers.

2. Annualised rate of severe COPD exacerbations. [104 weeks total (52 weeks in this study)]

   The annualised rate of severe COPD exacerbations over the treatment period. Analyses will be conducted in the former smoker population, followed by the Overall Population of current and former smokers.

3. Time to first moderate-to-severe COPD exacerbation. [104 weeks total (52 weeks in this study)]

   To explore the extent to which treatment with each dose of Tozorakimab delays the time to first exacerbation compared with placebo.

4. Annualised rate of moderate to severe COPD exacerbations. [104 weeks total (52 weeks in this study)]

   To evaluate the effect of Tozorakimab as an add on to SoC compared with SoC plus placebo on the rate of moderate to severe COPD exacerbations.

5. Time to all-cause death. [104 weeks total (52 weeks in this study)]

   To evaluate the effect of Tozorakimab as an add on to SoC compared with SoC plus placebo on time to all-cause death.

6. Trough serum concentrations of tozorakimab over the treatment period. [104 weeks total (52 weeks in this study)]

   Pharmacokinetics: concentrations of Tozorakimab in trough serum.

7. Incidence of anti-drug antibodies. [104 weeks total (52 weeks in this study)]

   Immunogenicity: presence of Tozorakimab anti-drug antibodies in blood serum.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years to 130 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Participants who have completed the treatment period and have not been prematurely discontinued from IP in the predecessor studies.

2. Participants who received their last dose of IP in the predecessor studies within the previous 12 weeks and were not withdrawn from the predecessor study.

3. FOCBP (female(s) of childbearing potential) must have a negative urine pregnancy test at Visit 1.

4. Participants who are willing to continue using contraceptive methods as agreed to for the predecessor OBERON or TITANIA studies.

5. Capable of giving signed informed consent.

Exclusion Criteria:

1. Any clinically significant disorder or abnormal findings (clinical, laboratory, instrumental, etc) or major physical and/or cognitive impairment - which, in the opinion of the Investigator, may put the participant at risk because of his/her participation in the study or impact the interpretation of the study results, or otherwise make the participation of the participant inappropriate.

2. Participant meeting criteria for IP discontinuation as judged by the Investigator or the Sponsor.

3. Concurrent enrolment in other interventional clinical studies or treatment with another IP, with the exception of the OBERON and TITANIA predecessor studies.

4. Known history of:

5. Severe allergic reaction to any monoclonal and polyclonal antibody.

6. Allergy or reaction to any component of the IP formulation.

7. Chronic use (or expected need for chronic use during the study) of immunosuppressive medications (including, but not limited to, systemic corticosteroids), marketed or investigational biologic, or another prohibited medication.

8. Involvement in the planning and/or conduct of the study (applies to both staff employed by the Sponsor and/or staff at the study site).

9. Participants who are not able to comply with the study requirements, procedures, and restrictions.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Lincoln	California	United States	95648
2	Research Site	Newport Beach	California	United States	92663
3	Research Site	Pensacola	Florida	United States	32501
4	Research Site	Tampa	Florida	United States	33607
5	Research Site	Normal	Illinois	United States	61761
6	Research Site	Bowling Green	Kentucky	United States	42101
7	Research Site	Zachary	Louisiana	United States	70791
8	Research Site	Gastonia	North Carolina	United States	28054
9	Research Site	Tulsa	Oklahoma	United States	74133
10	Research Site	Rock Hill	South Carolina	United States	29732
11	Research Site	Wollongong		Australia	2522
12	Research Site	Gent		Belgium	9000
13	Research Site	Leuven		Belgium	3000
14	Research Site	Liege		Belgium	4000
15	Research Site	Namur		Belgium	5101
16	Research Site	Blumenau		Brazil	89030-101
17	Research Site	Botucatu		Brazil	18618-686
18	Research Site	Brasilia		Brazil	71681-603
19	Research Site	Curitiba		Brazil	80440-220
20	Research Site	Porto Alegre		Brazil	90035074
21	Research Site	Rio de Janeiro		Brazil	22061-080
22	Research Site	Sao Bernardo do Campo		Brazil	09750-420
23	Research Site	Sao Paulo		Brazil	01323-903
24	Research Site	Sao Paulo		Brazil	05403-000
25	Research Site	São Paulo		Brazil	01409-001
26	Research Site	Brno		Czechia	625 00
27	Research Site	Broumov		Czechia	55001
28	Research Site	Jihlava		Czechia	586 33
29	Research Site	Jindrichuv Hradec		Czechia	377 01
30	Research Site	Liberec 1		Czechia	460 63
31	Research Site	Olomouc		Czechia	779 00
32	Research Site	Rokycany		Czechia	337 01
33	Research Site	Hvidovre		Denmark	2650
34	Research Site	København NV		Denmark	2400
35	Research Site	Næstved		Denmark	4700
36	Research Site	Roskilde		Denmark	4000
37	Research Site	Vejle		Denmark	7100
38	Research Site	Ålborg		Denmark	9000
39	Research Site	Helsinki		Finland	00290
40	Research Site	Hämeenlinna		Finland	13530
41	Research Site	Kuopio		Finland	70210
42	Research Site	Tampere		Finland	33520
43	Research Site	Turku		Finland	20100
44	Research Site	Turku		Finland	20520
45	Research Site	Bamberg		Germany	96049
46	Research Site	Berlin		Germany	10717
47	Research Site	Berlin		Germany	12157
48	Research Site	Darmstadt		Germany	64283
49	Research Site	Großhansdorf		Germany	22927
50	Research Site	Halle		Germany	06108
51	Research Site	Köln		Germany	51069
52	Research Site	Marburg		Germany	35037
53	Research Site	München-Pasing		Germany	81241
54	Research Site	Peine		Germany	31224
55	Research Site	Napoli		Italy	80131
56	Research Site	Roma		Italy	00168
57	Research Site	Salerno		Italy	84131
58	Research Site	Sassari		Italy	07100
59	Research Site	Tradate		Italy	21049
60	Research Site	Verona		Italy	37124
61	Research Site	Osaka-shi		Japan	531-0073
62	Research Site	Toshima-ku		Japan	170-0003
63	Research Site	Yokohama-shi		Japan	223-0059
64	Research Site	Harderwijk		Netherlands	3844
65	Research Site	Heerlen		Netherlands	6419 PC
66	Research Site	Zutphen		Netherlands	7207 AE
67	Research Site	Zwolle		Netherlands	8025 AB
68	Research Site	Bergen		Norway	5021
69	Research Site	Bodø		Norway	8092
70	Research Site	Lørenskog		Norway	1478
71	Research Site	Oslo		Norway	450
72	Research Site	Tønsberg		Norway	3103
73	Research Site	Godoy Cruz		Peru	5501
74	Research Site	Lima		Peru	15046
75	Research Site	Lima		Peru	15088
76	Research Site	Lima		Peru	L18
77	Research Site	Lima		Peru	L27
78	Research Site	Lima		Peru	LIMA 21
79	Research Site	Lima		Peru	LIMA 31
80	Research Site	Piura		Peru	20001
81	Research Site	Białystok		Poland	15-044
82	Research Site	Bydgoszcz		Poland	85-796
83	Research Site	Katowice		Poland	40-648
84	Research Site	Krakow		Poland	30-033
85	Research Site	Lublin		Poland	20-412
86	Research Site	Ostrowiec Świętokrzyski		Poland	27-400
87	Research Site	Poznań		Poland	60-693
88	Research Site	Poznań		Poland	61-578
89	Research Site	Rzeszów		Poland	35-205
90	Research Site	Wroclaw		Poland	54-239
91	Research Site	Lisboa		Portugal	1649-035
92	Research Site	Lisboa		Portugal	1998-018
93	Research Site	Galdakao		Spain	48960
94	Research Site	Madrid		Spain	28040
95	Research Site	Malaga		Spain	29010
96	Research Site	Mérida		Spain	06800
97	Research Site	Pozuelo de Alarcon		Spain	28223
98	Research Site	Santander		Spain	39008
99	Research Site	Valencia		Spain	46010
100	Research Site	Zaragoza		Spain	50009
101	Research Site	Göteborg		Sweden	413 46
102	Research Site	Göteborg		Sweden	41345
103	Research Site	Lund		Sweden	222 22
104	Research Site	Malmö		Sweden	205 02
105	Research Site	Stockholm		Sweden	11239
106	Research Site	Bang Kra So		Thailand	11000
107	Research Site	Bangkok		Thailand	10700
108	Research Site	Hat Yai		Thailand	90110
109	Research Site	Khon Kaen		Thailand	40002
110	Research Site	Muang,		Thailand	55000
111	Research Site	Mueang		Thailand	20000
112	Research Site	Hanoi		Vietnam	100000
113	Research Site	Hanoi		Vietnam	10000
114	Research Site	Ho Chi Minh		Vietnam	700000

Sponsors and Collaborators

• AstraZeneca

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT05742802
• Other Study ID Numbers: D9180C00008; 2022-501063-41-00
• First Posted: Feb 24, 2023
• Last Update Posted: Feb 24, 2023
• Last Verified: Feb 1, 2023

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by AstraZeneca: Chronic Obstructive Pulmonary Disease; COPD; Tozorakimab; MEDI3506; exacerbations; ICS; LABA/LAMA
• Additional relevant MeSH terms: Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive

Study Results

No Results Posted as of Feb 24, 2023