TITANIA: Efficacy and Safety of Tozorakimab in Symptomatic Chronic Obstructive Pulmonary Disease With a History of Exacerbations.

Sponsor

AstraZeneca (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05158387

Collaborator

(none)

1,272

Enrollment

240

Locations

Arms

42.6

Anticipated Duration (Months)

5.3

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this Phase III study is to evaluate the efficacy and safety of tozorakimab Dose 1 and Dose 2 administered subcutaneously (SC) in adult participants with symptomatic COPD and history of ≥ 2 moderate or ≥ 1 severe exacerbation of COPD in the previous 12 months. Participants should be receiving optimised treatment with maintenance inhaled therapy (ICS/LABA/LAMA triple therapy, or dual therapy if triple is not considered appropriate) in stable doses throughout at least 3 months prior to enrolment.

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

Study Design

Study Type:

Interventional

Anticipated Enrollment :

1272 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Masking Description:

unblinded administrator/pharmacist

Primary Purpose:

Treatment

Official Title:

A Phase III, Multicentre, Randomised, Double-blind, Chronic-dosing, Parallel-group, Placebo-controlled Study to Evaluate the Efficacy and Safety of Two Dose Regimens of Tozorakimab in Participants With Symptomatic Chronic Obstructive Pulmonary Disease (COPD) With a History of COPD Exacerbations (TITANIA)

Actual Study Start Date :

Feb 7, 2022

Anticipated Primary Completion Date :

Jun 5, 2025

Anticipated Study Completion Date :

Aug 28, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Tozorakimab Dose 1 Dosing subcutaneously tozorakimab Dose 1 and placebo	Drug: Tozorakimab Administered subcutaneously tozorakimab Dose 1 and placebo through Week 52.
Experimental: Tozorakimab Dose 2 Dosing subcutaneously tozorakimab Dose 2	Drug: Tozorakimab Administered subcutaneously tozorakimab Dose 2 through Week 52.
Placebo Comparator: Placebo Dosing subcutaneously with equivalent volume to tozorakimab	Drug: Placebo Placebo administered subcutaneously, equivalent volume to tozorakimab through week 52.

Arm

Intervention/Treatment

Experimental: Tozorakimab Dose 1

Dosing subcutaneously tozorakimab Dose 1 and placebo

Drug: Tozorakimab

Administered subcutaneously tozorakimab Dose 1 and placebo through Week 52.

Experimental: Tozorakimab Dose 2

Dosing subcutaneously tozorakimab Dose 2

Drug: Tozorakimab

Administered subcutaneously tozorakimab Dose 2 through Week 52.

Placebo Comparator: Placebo

Dosing subcutaneously with equivalent volume to tozorakimab

Drug: Placebo

Placebo administered subcutaneously, equivalent volume to tozorakimab through week 52.

Outcome Measures

Primary Outcome Measures

Annualized rate of moderate to severe COPD exacerbations in participants who are former smokers. [over 52 weeks]
The primary endpoint will be assessed first in the primary population (former smokers with symptomatic COPD and a history of exacerbations, on optimised treatment with maintenance inhaled therapy [triple therapy, or dual therapy if triple is not considered appropriate]) and then assessed in the overall population of participants.

Secondary Outcome Measures

Annualized rate of moderate to severe COPD exacerbations in former or current smokers. [over 52 weeks]
The annualized rate will be assessed in the overall population of participants including current and former smokers with symptomatic COPD and history of exacerbations, on optimised treatment with maintenance inhaled therapy.
Time to first moderate to severe COPD exacerbation in former smokers. [over 52 weeks]
To explore the extent to which treatment with each dose of tozorakimab delays the time to first exacerbation compared with placebo in former smokers.
Mean change from baseline in pre-BD, pre-dose trough FEV1 (mL) in former smokers. [Week 52, or over 52 weeks]
Change from baseline in pre-bronchodilator, pre dose trough FEV1 (mL) in former smokers.
Mean change from baseline in pre-BD, pre-dose trough FEV1 (mL) in the overall population of current and former smokers. [Week 52, or over 52 weeks]
Change from baseline in pre-bronchodilator, pre dose trough FEV1 (mL) in the overall population of current and former smokers.
Percentage of responders achieving MCID in E-RS:COPD total score in former smokers [Week 52]
Responder analyses for E-RS:COPD total score at Week 52 based upon a ≥ 2 point improvement (decrease) from baseline in former smokers.
Percentage of responders achieving MCID in E-RS:COPD total score in the overall population of current and former smokers. [Week 52]
Responder analyses for E-RS:COPD total score at Week 52 based upon a ≥ 2 point improvement (decrease) from baseline in the overall population of current and former smokers.
Mean change from baseline in E-RS:COPD total score in former smokers. [over 52 weeks]
Difference in mean change in E-RS:COPD total score from baseline in former smokers.
Mean change from baseline in E-RS:COPD total score in the overall population of current and former smokers. [over 52 weeks]
Difference in mean change in E-RS:COPD total score from baseline in the overall population of current and former smokers.
Percentage of responders achieving MCID in SGRQ total score in former smokers. [Week 52]
Percentage of participants with a decrease in SGRQ total score of ≥ 4 points from baseline in former smokers.
Percentage of responders achieving MCID in SGRQ total score in the overall population of current and former smokers. [Week 52]
Percentage of participants with a decrease in SGRQ total score of ≥ 4 points from baseline in the overall population of current and former smokers.
Mean change from baseline in SGRQ total score from in former smokers. [over 52 weeks]
Difference in mean change from baseline in SGRQ total score in former smokers.
Mean change from baseline in SGRQ total score from in the overall population of current and former smokers. [over 52 weeks]
Difference in mean change from baseline in SGRQ total score in the overall population of current and former smokers.
Time to first severe COPD exacerbation in former smokers. [over 52 weeks]
To evaluate hazard ratio of first severe COPD exacerbation in former smokers.
Annualized rate of severe COPD exacerbations in former smokers. [over 52 weeks]
The rate ratio of severe COPD exacerbations will be assessed in former smokers.
Change from baseline in CAT total score. [Week 52]
Analyses of change from baseline in CAT total score in former smokers.
Percentage of participants with a decrease in CAT total score in former smokers. [Week 52]
Proportion of participants achieving MCID in CAT total score, a decrease in CAT total score of ≥ 2 points from baseline in former smokers.
Proportion of participants having ≥ 1 healthcare resource utilization type in former smokers. [over 52 weeks]
Proportion of participants having ≥ 1 healthcare resource utilization type in former smokers.
Annualized rate of healthcare resource utilization in former smokers. [over 52 weeks]
Annualized rate of healthcare resource utilization in former smokers.
The change from baseline in mean number of puffs per day in rescue use in former smokers. [over 52 weeks]
Difference in mean number of puffs per day from baseline.
Trough serum concentrations of tozorakimab. [over 52 weeks]
Pharmacokinetics: concentrations of tozorakimab in trough serum.
Presence of anti-drug antibodies. [over 60 weeks]
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:

Inclusion Criteria:

Participant must be ≥ 40 years of age and capable of giving signed informed consent.
Documented diagnosis of COPD for at least one year prior to enrolment.
Post BD FEV1/FVC < 0.70 and post-BD FEV1 >20% of predicted normal value.
Documented history of ≥ 2 moderate or ≥ 1 severe COPD exacerbations within 12 months prior to enrolment.
Documented optimized inhaled dual or triple therapy at a stable dose for at least 3 months prior to enrolment.
Smoking history of ≥ 10 pack-years.
CAT total score ≥10, with each of the phlegm (sputum) and cough items with a score ≥ 2

Exclusion Criteria:

Clinically important pulmonary disease other than COPD.
Radiological findings suggestive of a respiratory disease other than COPD that is contributing to the participant's respiratory symptoms.
Current diagnosis of asthma, prior history of asthma, or asthma-COPD overlap. Childhood history of asthma is allowed and defined as asthma diagnosed and resolved before the age of 18.
Any unstable disorder, including, but not limited to, cardiovascular, gastrointestinal, hepatic, renal, neurological, musculoskeletal, infectious, endocrine, metabolic, haematological, psychiatric disorder, major physical and/or cognitive impairment that could affect safety, study findings or participants ability to complete the study.
COPD exacerbation, within 2 weeks prior to randomization, that was treated with systemic corticosteroids and/or antibiotics, and/or led to hospitalization.
Active significant infection within the 4 weeks prior to randomization, pneumonia within 6 weeks prior to randomization, or medical condition that predisposes the participant to infection.
Suspicion of, or confirmed, ongoing SARS-CoV-2 infection.
Significant COVID-19 illness within the 6 months prior to enrolment.
Unstable cardiovascular disorder.
Diagnosis of cor pulmonale, pulmonary arterial hypertension and/or right ventricular failure.
History of known immunodeficiency disorder, including a positive test for HIV-1 or HIV
History of positive test or treatment for hepatitis B or hepatitis C (except for cured hepatitis C).
Evidence of active liver disease, including jaundice during screening.
Malignancy, current or within the past 5 years, except for adequately treated non-invasive basal cell and squamous cell carcinoma of the skin and cervical carcinoma-in-situ treated with apparent success more than one year prior to enrolment. Suspected malignancy or undefined neoplasms.
Participants who have evidence of active TB.
Participants that have previously received tozorakimab.
Any clinically significant abnormal findings in physical examination, vital signs, ECG, or laboratory testing during the screening period, which in the opinion of the investigator may put the participant at risk because of their participation in the study, or may influence the results of the study, or the participant's ability to complete the entire duration of the study.
Active vaping of any products within the 6 months prior to randomization and during the study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Sheffield	Alabama	United States	35660
2	Research Site	Fullerton	California	United States	92835
3	Research Site	Lincoln	California	United States	95648
4	Research Site	Newport Beach	California	United States	92663
5	Research Site	Northridge	California	United States	91324
6	Research Site	San Diego	California	United States	92120
7	Research Site	Colorado Springs	Colorado	United States	80909
8	Research Site	Newark	Delaware	United States	19713
9	Research Site	Bay Pines	Florida	United States	33744
10	Research Site	Pensacola	Florida	United States	32501
11	Research Site	Tampa	Florida	United States	33607
12	Research Site	Winter Park	Florida	United States	32789
13	Research Site	Macon	Georgia	United States	31201
14	Research Site	Greenwood	Indiana	United States	46143
15	Research Site	Bowling Green	Kentucky	United States	42101
16	Research Site	New Orleans	Louisiana	United States	70112
17	Research Site	North Dartmouth	Massachusetts	United States	02747
18	Research Site	Ann Arbor	Michigan	United States	48109
19	Research Site	Farmington Hills	Michigan	United States	48336
20	Research Site	Grand Rapids	Michigan	United States	49546
21	Research Site	Hannibal	Missouri	United States	63401
22	Research Site	Bellevue	Nebraska	United States	68123
23	Research Site	Bronx	New York	United States	10459
24	Research Site	Buffalo	New York	United States	14203
25	Research Site	Oklahoma City	Oklahoma	United States	73112
26	Research Site	Tulsa	Oklahoma	United States	74133
27	Research Site	Philadelphia	Pennsylvania	United States	19140
28	Research Site	Rock Hill	South Carolina	United States	29732
29	Research Site	Amarillo	Texas	United States	79106
30	Research Site	Boerne	Texas	United States	78006
31	Research Site	Fort Worth	Texas	United States	76104
32	Research Site	McKinney	Texas	United States	75069
33	Research Site	Tomball	Texas	United States	77375
34	Research Site	Webster	Texas	United States	77598
35	Research Site	Salt Lake City	Utah	United States	84102
36	Research Site	Williamsburg	Virginia	United States	23188
37	Research Site	Adelaide		Australia	5000
38	Research Site	Campbelltown		Australia	2560
39	Research Site	Frankstown		Australia	3199
40	Research Site	Macquarie University		Australia	2109
41	Research Site	Melbourne		Australia	3000
42	Research Site	Southport		Australia	4215
43	Research Site	Spearwood		Australia	6163
44	Research Site	Wollongong		Australia	2522
45	Research Site	Blumenau		Brazil	89030-101
46	Research Site	Botucatu		Brazil	18618-686
47	Research Site	Brasilia		Brazil	71681-603
48	Research Site	Curitiba		Brazil	80440-220
49	Research Site	Porto Alegre		Brazil	09101-004
50	Research Site	Porto Alegre		Brazil	90035074
51	Research Site	Porto Alegre		Brazil	9061-000
52	Research Site	Rio de Janeiro		Brazil	22061-080
53	Research Site	Sao Bernardo do Campo		Brazil	09750-420
54	Research Site	Sao Paulo		Brazil	01323-903
55	Research Site	Sao Paulo		Brazil	05403-000
56	Research Site	São Paulo		Brazil	01409-001
57	Research Site	Curico		Chile	3341643
58	Research Site	Santiago		Chile	7500010
59	Research Site	Santiago		Chile	7500692
60	Research Site	Santiago		Chile	7500698
61	Research Site	Santiago		Chile	8150000
62	Research Site	Santiago		Chile	8241479
63	Research Site	Talca		Chile	3465584
64	Research Site	Baotou		China	014010
65	Research Site	Beijing		China	100034
66	Research Site	Beijing		China	100050
67	Research Site	Beijing		China	100144
68	Research Site	Changchun		China
69	Research Site	Changde		China	415003
70	Research Site	Changsha		China	410015
71	Research Site	Chengdu		China	610000
72	Research Site	Chengdu		China	610031
73	Research Site	Chengdu		China	610083
74	Research Site	Chongqing		China	400037
75	Research Site	Guangzhou		China	510120
76	Research Site	Guangzhou		China	510180
77	Research Site	Guangzhou		China	510630
78	Research Site	Haikou		China	570311
79	Research Site	Hangzhou		China	310006
80	Research Site	Hefei		China	230001
81	Research Site	Hohhot		China	010017
82	Research Site	Kunming		China	650032
83	Research Site	Linhai		China	317000
84	Research Site	Nanchang		China	330006
85	Research Site	Nanjing		China	210000
86	Research Site	Nanjing		China	210006
87	Research Site	Ningbo		China	315010
88	Research Site	Shanghai		China	200002
89	Research Site	Shanghai		China	200032
90	Research Site	Shanghai		China	200433
91	Research Site	Shanghai		China	201199
92	Research Site	Shengyang		China	110004
93	Research Site	Shenyang		China	110016
94	Research Site	Shenzhen		China	518020
95	Research Site	Shenzhen		China	518053
96	Research Site	Shijiazhuang		China	50051
97	Research Site	Suzhou		China	215002
98	Research Site	Suzhou		China	215004
99	Research Site	Taiyuan		China	030001
100	Research Site	Tianjin		China	300052
101	Research Site	Urumqi		China	830054
102	Research Site	Wuhan		China	430022
103	Research Site	Wuxi		China	214023
104	Research Site	Xiamen		China	361004
105	Research Site	Xuzhou		China	221000
106	Research Site	Xuzhou		China	221009
107	Research Site	Yangzhou		China	225001
108	Research Site	Yinchuan		China	750001
109	Research Site	Yinchuan		China	750004
110	Research Site	Zhanjiang		China	524004
111	Research Site	Zunyi		China	563100
112	Research Site	Barranquilla		Colombia	80007
113	Research Site	Bogotá		Colombia	111211
114	Research Site	Ibague		Colombia	730006
115	Research Site	Medellin		Colombia	050034
116	Research Site	Rionegro		Colombia	54040
117	Research Site	Brest Cedex 2		France	29609
118	Research Site	Dijon Cedex		France	21079
119	Research Site	Grenoble cedex 9		France	38043
120	Research Site	Limoges		France	87042
121	Research Site	Lyon Cedex		France	69317
122	Research Site	Marseille		France	13915
123	Research Site	Montivilliers		France	76290
124	Research Site	Montpellier Cedex		France	34295
125	Research Site	Nantes		France	44093
126	Research Site	Pessac		France	33604
127	Research Site	Toulouse		France	31059
128	Research Site	Bamberg		Germany	96049
129	Research Site	Berlin		Germany	10717
130	Research Site	Berlin		Germany	12157
131	Research Site	Darmstadt		Germany	64283
132	Research Site	Frankfurt		Germany	60596
133	Research Site	Großhansdorf		Germany	22927
134	Research Site	Halle		Germany	6108
135	Research Site	Köln		Germany	51069
136	Research Site	Marburg		Germany	35037
137	Research Site	München-Pasing		Germany	81241
138	Research Site	München		Germany	80336
139	Research Site	Peine		Germany	31224
140	Research Site	Alexandroupolis		Greece	68100
141	Research Site	Athens		Greece	11527
142	Research Site	Exohi Thessaloniki		Greece	57010
143	Research Site	Ioannina		Greece	45500
144	Research Site	Patras		Greece	26500
145	Research Site	Thessaloniki		Greece	57010
146	Research Site	Ashkelon		Israel	78278
147	Research Site	Beer Sheva		Israel	8410101
148	Research Site	Haifa		Israel	34362
149	Research Site	Jerusalem		Israel	91120
150	Research Site	Jerusalem		Israel	9372212
151	Research Site	Rehovot		Israel	76100
152	Research Site	Tel Aviv		Israel	6423906
153	Research Site	Macerata		Italy	62100
154	Research Site	Messina		Italy	98124
155	Research Site	Milano		Italy	20142
156	Research Site	Milano		Italy	20157
157	Research Site	Napoli		Italy	80131
158	Research Site	Roma		Italy	00168
159	Research Site	Salerno		Italy	84131
160	Research Site	San Donà di Piave		Italy	30027
161	Research Site	Sassari		Italy	07100
162	Research Site	Tradate		Italy	21049
163	Research Site	Vercelli		Italy	13100
164	Research Site	Verona		Italy	37124
165	Research Site	Lima		Peru	15036
166	Research Site	Lima		Peru	15046
167	Research Site	Lima		Peru	15088
168	Research Site	Lima		Peru	L18
169	Research Site	Lima		Peru	LIMA 21
170	Research Site	Lima		Peru	LIMA 31
171	Research Site	Piura		Peru	20001
172	Research Site	Baguio		Philippines	2600
173	Research Site	Cebu City		Philippines	6000
174	Research Site	Iloilo City		Philippines	5000
175	Research Site	Iloilo City		Philippines	5000
176	Research Site	Manila		Philippines	1000
177	Research Site	Białystok		Poland	15-044
178	Research Site	Białystok		Poland	15-430
179	Research Site	Bydgoszcz		Poland	85-796
180	Research Site	Gdańsk		Poland	80-214
181	Research Site	Grudziądz		Poland	86-300
182	Research Site	Katowice		Poland	40-648
183	Research Site	Krakow		Poland	30-033
184	Research Site	Kraków		Poland	31-559
185	Research Site	Lublin		Poland	20-412
186	Research Site	Nowa Sól		Poland	67-100
187	Research Site	Ostrowiec Świętokrzyski		Poland	27-400
188	Research Site	Ostróda		Poland	14-100
189	Research Site	Poznań		Poland	60-693
190	Research Site	Poznań		Poland	61-578
191	Research Site	Rzeszów		Poland	35-205
192	Research Site	Skierniewice		Poland	96-100
193	Research Site	Sosnowiec		Poland	41-208
194	Research Site	Wołomin		Poland	05-200
195	Research Site	Wroclaw		Poland	54-239
196	Research Site	Wrocław		Poland	53-301
197	Research Site	Caguas		Puerto Rico	00726
198	Research Site	Ponce		Puerto Rico	00716
199	Research Site	Brasov		Romania	500283
200	Research Site	Bucharest		Romania	50159
201	Research Site	Cluj-Napoca		Romania	400371
202	Research Site	Iasi		Romania	700304
203	Research Site	Timisoara		Romania	300002
204	Research Site	Chelyabinsk		Russian Federation	454106
205	Research Site	Izhevsk		Russian Federation	426061
206	Research Site	Moscow		Russian Federation	105077
207	Research Site	Moscow		Russian Federation	107150
208	Research Site	Novosibirsk		Russian Federation	630008
209	Research Site	Penza		Russian Federation	440067
210	Research Site	Perm		Russian Federation	614000
211	Research Site	Saint Petersburg		Russian Federation	194354
212	Research Site	Saratov		Russian Federation	410012
213	Research Site	Tomsk		Russian Federation	634034
214	Research Site	Ulyanovsk		Russian Federation	432009
215	Research Site	Hsinchu		Taiwan	300
216	Research Site	Kaohsiung		Taiwan	807
217	Research Site	Kaohsiung		Taiwan	82445
218	Research Site	Taichung		Taiwan	40443
219	Research Site	Taichung		Taiwan	40705
220	Research Site	Taipei		Taiwan	100
221	Research Site	Taoyuan		Taiwan	333
222	Research Site	Yunlin		Taiwan	640
223	Research Site	Bang Kra So		Thailand	11000
224	Research Site	Bangkok		Thailand	10700
225	Research Site	Hat Yai		Thailand	90110
226	Research Site	Khon Kaen		Thailand	40000
227	Research Site	Khon Kaen		Thailand	40002
228	Research Site	Muang,		Thailand	55000
229	Research Site	Blackpool		United Kingdom	FY4 3AD
230	Research Site	Bradford		United Kingdom	BD9 6RJ
231	Research Site	Corby		United Kingdom	NN17 2UR
232	Research Site	Corby		United Kingdom	NN18 9EZ
233	Research Site	Enfield		United Kingdom	EN3 4GS
234	Research Site	Hampshire		United Kingdom	SO16 6YD
235	Research Site	High Wycombe		United Kingdom	HP11 2QW
236	Research Site	Newcastle upon Tyne		United Kingdom	NE7 7DN
237	Research Site	Northwood		United Kingdom	HA6 2RN
238	Research Site	Preston		United Kingdom	PR2 9QB
239	Research Site	Shipley		United Kingdom	BD18 3SA
240	Research Site	Wokingham		United Kingdom	RG40 1XS