Study of Reslizumab in Participants With Uncontrolled Asthma and Elevated Blood Eosinophils

• Sponsor: Teva Branded Pharmaceutical Products R&D, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02452190
• Collaborator: PPD (Industry)
• Enrollment: 468
• Locations: 226
• Arms: 2
• Actual Duration (Months): 28.1
• Patients Per Site: 2.1
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The primary objective of this study is to determine the effect of reslizumab (110 mg) administered subcutaneously every 4 weeks on clinical asthma exacerbations in adults and adolescents with asthma and elevated blood eosinophils who are inadequately controlled on standard-of-care asthma therapy.

Condition or Disease	Intervention/Treatment	Phase
Asthma	Drug: Reslizumab; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 468 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A 52-Week Double-Blind, Placebo-Controlled, Parallel-Group Efficacy and Safety Study of Reslizumab 110 mg Fixed, Subcutaneous Dosing in Patients With Uncontrolled Asthma and Elevated Blood Eosinophils
• Actual Study Start Date: Sep 28, 2015
• Actual Primary Completion Date: Dec 4, 2017
• Actual Study Completion Date: Jan 31, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Reslizumab Reslizumab	Drug: Reslizumab; Reslizumab will be administered subcutaneously in a dose of 110 mg every 4 weeks.
Placebo Comparator: Placebo Matching Placebo	Drug: Placebo; Matching Placebo

Outcome Measures

Primary Outcome Measures

1. Number of Clinical Asthma Exacerbations (CAEs) During 52 Weeks of Treatment [Day 1 to Week 52]

   A CAE was defined as a clinically-judged deterioration in asthma control, as determined by the investigator and as evidenced by new or worsening asthma signs or symptoms based on the participant's history, asthma control diary, physical examination, and/or ambulatory or clinic visit assessment of lung function and that resulted in a medical intervention, including at least 1 of the following: 1) use of systemic corticosteroids (oral or injection) or at least a doubling from a stable maintenance oral corticosteroid dose for at least 3 days; 2) asthma-specific hospital admission; 3) asthma-specific emergency department visit. Adjusted CAE rate and confidence intervals were based on Negative Binomial regression model adjusted for stratification factors. Results are presented as adjusted means. For this analysis, the offset variable is calculated as the logarithm of treatment duration minus the summed duration of exacerbations during the treatment period.

Secondary Outcome Measures

1. Change From Baseline to Week 52 in Pre-bronchodilator Forced Expiratory Volume in 1 Second (FEV1) [Baseline, Week 52]

   Change in pre-bronchodilator FEV1 from baseline to week 52 is presented. FEV1 is a standard measurement of air movement in the lungs of participants with asthma obtained from pulmonary function tests. It is the volume of air expired in the first second of a forced expiration using a spirometer. Analysis of the change from baseline to each visit was performed using a mixed effect model for repeated measures (MMRM) including fixed effects for treatment, visit, treatment by visit interaction, age group, blood eosinophil counts at enrollment, and sex, height and baseline value as covariates, and participant as a random effect.

2. Change From Baseline to Week 52 in Asthma Quality of Life Questionnaire for Participants 12 Years and Older (AQLQ+12) Score [Baseline, Week 52]

   AQLQ is a 32-item instrument administered as a self-assessment. AQLQ+12 is a modified version of AQLQ developed to measure functional impairments of participants aged 12-70 years. It is divided into 4 domains: activity limitation, symptoms, emotional function, and environmental stimuli. Participants were asked to recall their experiences during the last 2 weeks and respond to each question on a 7-point scale (1=severe impairment, 7=no impairment), where higher scores indicated "better quality of life." Overall AQLQ+12 score is the mean of all 32 responses. Analysis of the change from baseline to each visit was performed using a MMRM including fixed effects for treatment, visit, treatment by visit interaction, age group, blood eosinophil counts at enrollment, and sex, height and baseline value as covariates, and participant as a random effect.

3. Change From Baseline to Week 52 in 6-item Asthma Control Questionnaire (ACQ-6) Score [Baseline, Week 52]

   The ACQ-6 is a 6-item validated asthma assessment tool that has been widely used. Six questions are self-assessments (completed by the participant), 5 questions assessing asthma symptoms: night-time waking, symptoms on waking, activity limitation, shortness of breath, wheezing, and 1 question for short-acting bronchodilator use. Each item on the ACQ-6 has a possible score ranges from 0 to 6, and the total score is the mean of all responses. The total score ranging from 0-6 (0=totally controlled and 6=severely uncontrolled). A higher score indicated poorer asthma control. Analysis of the change from baseline to each visit was performed using a mixed effect model for repeated measures (MMRM) including fixed effects for treatment, visit, treatment by visit interaction, age group, blood eosinophil counts at enrollment, and sex, height and baseline value as covariates, and participant as a random effect.

4. Change From Baseline to Week 52 in Total Asthma Symptom Scores (Day and Night) [Baseline, Week 52]

   Asthma symptoms were recorded by participant each day and night in an asthma control diary. Night score was assessed on a 5-point scale where 0=no symptoms, slept through night, to 4=bad night, no sleep. Day score was assessed on a 6-point scale where 0=very well, no symptoms, to 5= asthma very severe, unable to carry out daily activities. Total asthma symptom score was calculated by taking the sum of the night and day asthma symptom scores recorded, ranging from 0 (no symptom) to 9 (severe symptom). A lower symptom score indicated a better outcome. Analysis of the change from baseline to each visit was performed using a MMRM including fixed effects for treatment, visit, treatment by visit interaction, age group, blood eosinophil counts at enrollment, and sex, height and baseline value as covariates, and participant as a random effect.

5. Percentage of Asthma Control Days [Day 1 to Week 52]

   The percentage of asthma control days over 52 weeks of treatment is presented. An asthma control day was defined as a day on which the participant used less than or equal to 2 puffs of inhaled short-acting beta-agonist, had no nighttime awakenings, and experienced no asthma exacerbations. Analysis of the change from baseline to each visit was performed using a mixed effect MMRM including fixed effects for treatment, visit, treatment by visit interaction, age group, blood eosinophil counts at enrollment, and sex, height and baseline value as covariates, and participant as a random effect.

6. Change From Baseline to Week 32 in St. George's Respiratory Questionnaire (SGRQ) Total Score [Baseline, Week 32]

   The SGRQ is a 17-item questionnaire with 50 weighted responses. It provides a total score and three component scores: Symptoms (distress caused by respiratory symptoms), Activity (physical activities that cause or are limited by breathlessness), and Impacts (social and psychological effects of the disease). The total score and each of the SGRQ subscores are scored from 0 to 100 where 0 indicates best and 100 indicates worst health. An increase in score indicates worsening health. Analysis of the change from baseline to each visit was performed using a mixed effect model for repeated measures (MMRM) including fixed effects for treatment, visit, treatment by visit interaction, age group, blood eosinophil counts at enrollment, and sex, height and baseline value as covariates, and participant as a random effect.

7. Kaplan-Meier (K-M) Estimate of Probability (Percent [%]) of Not Experiencing a CAE by Week 52 [Day 1 to Week 52]

   CAE was defined as a clinically judged deterioration in asthma control, as determined by the investigator and as evidenced by new or worsening asthma signs or symptoms based on the participant's history, asthma control diary, physical examination, and/or ambulatory or clinic visit assessment of lung function and that resulted in a medical intervention, including at least 1 of the following: 1) use of systemic corticosteroids (oral or injection) or at least a doubling from a stable maintenance oral corticosteroid dose for at least 3 days; 2) asthma-specific hospital admission; 3) asthma-specific emergency department visit. The KM method was used to estimate and compare the distributions of time to first CAE between treatment groups. Participants without an event during the treatment period were censored at either the date of the end of treatment (Week 52) visit for participants who completed treatment or at the date of last dose (+4 weeks) for participants who discontinued early.

8. Number of CAEs Requiring Hospitalization and/or Emergency Department Visits During 52 Weeks of Treatment [Day 1 to Week 52]

   A CAE was defined as a clinically judged deterioration in asthma control, as determined by the investigator and as evidenced by new or worsening asthma signs or symptoms based on the participant's history, asthma control diary, physical examination, and/or ambulatory or clinic visit assessment of lung function and that resulted in a medical intervention, including at least 1 of the following: 1) use of systemic corticosteroids (oral or injection) or at least a doubling from a stable maintenance oral corticosteroid dose for at least 3 days; 2) asthma-specific hospital admission; 3) asthma-specific emergency department visit. The frequency of CAEs over 52-week treatment period is expressed as adjusted CAEs rate in 52 weeks. Adjusted CAE rate and confidence intervals were based on Negative Binomial regression model adjusted for stratification factors (age group, blood eosinophil group) and number of prior exacerbations, and an offset variable.

9. Number of Moderate Exacerbations During 52 Weeks of Treatment [Day 1 to Week 52]

   A moderate exacerbation was defined as a clinically judged deterioration in asthma control as determined by investigator and as evidenced by new or worsening asthma signs or symptoms based on the participant's history, asthma control diary, physical examination, and/or ambulatory or clinic visit assessment of lung function and that resulted in a medical intervention requiring additional asthma controller medication that was not a systemic corticosteroid and did not result in an asthma-specific hospitalization or emergency department visit (that is, a medical intervention that did not otherwise meet the criteria for primary endpoint). Frequency of moderate exacerbations over 52-week treatment period is expressed as adjusted exacerbation rate in 52 weeks. Adjusted exacerbation rate and confidence intervals were based on Negative Binomial regression model adjusted for stratification factors (age group, blood eosinophil group) and number of prior exacerbations, and an offset variable.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Written informed consent is obtained.

• The participant is male or female, 12 years of age and older, with a diagnosis of asthma.

• The participant has Forced Expiratory Volume in 1 Second (FEV1) reversibility according to standard American Thoracic Society (ATS) or European Respiratory Society (ERS) protocol.

• The participant has required an inhaled corticosteroid.

• The participant has required an additional asthma controller medication besides inhaled corticosteroids.

• The participant has a history of asthma exacerbation.

• The participant must be willing and able to comply with study restrictions, perform requisite procedures and remain at the clinic for the required duration during the study period, and be willing to return to the clinic for the follow-up evaluation as specified in this protocol.

• Additional criteria may apply, please contact the investigator for more information

Exclusion Criteria:

• The participant has any clinically significant, uncontrolled medical condition (treated or untreated) that would interfere with the study schedule or procedures, interpretation of efficacy results, or compromise the patient's safety.

• The participant has another confounding underlying lung disorder

• The participant has a known hypereosinophilic syndrome.

• The participant has a diagnosis of malignancy within 5 years of the screening visit, except for treated and cured non-melanoma skin cancers.

• The participant is a pregnant or lactating woman, or intends to become pregnant during the study. Any woman becoming pregnant during the study will be withdrawn from the study.

• The participant is a current smoker or has a smoking history.

• The participated in a clinical trial within 30 days or 5 half-lives of the investigational drug before screening, whichever is longer.

• The participant was previously exposed to reslizumab.

• The participant has a history of an immunodeficiency disorder including human immunodeficiency virus (HIV).

• The participant has current or suspected drug and alcohol abuse.

• The participant has an active helminthic parasitic infection or was treated for one within 6 months of screening.

• The participant has a history of allergic reaction or hypersensitivity to any component of the study drug.

• Additional criteria may apply, please contact the investigator for more information

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Teva Investigational Site 13212	Birmingham	Alabama	United States	35209
2	Teva Investigational Site 13241	Flagstaff	Arizona	United States	86001
3	Teva Investigational Site 13194	Glendale	Arkansas	United States	85306
4	Teva Investigational Site 13215	Bakersfield	California	United States	93301
5	Teva Investigational Site 13181	Canoga Park	California	United States	91303
6	Teva Investigational Site 13254	Fresno	California	United States	93720
7	Teva Investigational Site 13216	Huntington Beach	California	United States	92647
8	Teva Investigational Site 13247	Long Beach	California	United States	90813
9	Teva Investigational Site 13205	Napa	California	United States	94558
10	Teva Investigational Site 13764	San Jose	California	United States	95117
11	Teva Investigational Site 13252	Stockton	California	United States	95207
12	Teva Investigational Site 13251	Walnut Creek	California	United States	94598
13	Teva Investigational Site 13229	Denver	Colorado	United States	80206
14	Teva Investigational Site 13766	Waterbury	Connecticut	United States	06708
15	Teva Investigational Site 13196	Aventura	Florida	United States	33180
16	Teva Investigational Site 13256	Fort Lauderdale	Florida	United States	33308
17	Teva Investigational Site 13203	Kissimmee	Florida	United States	34741
18	Teva Investigational Site 13197	Miami	Florida	United States	33125
19	Teva Investigational Site 13220	Miami	Florida	United States	33155
20	Teva Investigational Site 13243	Miami	Florida	United States	33176
21	Teva Investigational Site 13233	New Port Richey	Florida	United States	34653
22	Teva Investigational Site 13201	Orlando	Florida	United States	32811
23	Teva Investigational Site 13250	Orlando	Florida	United States	32819
24	Teva Investigational Site 13246	Pembroke Pines	Florida	United States	33029
25	Teva Investigational Site 13208	Tallahassee	Florida	United States	32308
26	Teva Investigational Site 13255	Tampa	Florida	United States	33607
27	Teva Investigational Site 13765	Albany	Georgia	United States	31707
28	Teva Investigational Site 13249	Buford	Georgia	United States	30518
29	Teva Investigational Site 13763	Lawrenceville	Georgia	United States	30045
30	Teva Investigational Site 13230	Chicago	Illinois	United States	60612
31	Teva Investigational Site 13211	Normal	Illinois	United States	61761
32	Teva Investigational Site 13235	Shiloh	Illinois	United States	62269
33	Teva Investigational Site 13202	Michigan City	Indiana	United States	46360
34	Teva Investigational Site 13225	Lenexa	Kansas	United States	66215
35	Teva Investigational Site 13222	Owensboro	Kentucky	United States	42301
36	Teva Investigational Site 13191	Lafayette	Louisiana	United States	70503
37	Teva Investigational Site 13200	North Dartmouth	Massachusetts	United States	02747
38	Teva Investigational Site 13226	Biloxi	Mississippi	United States	39531
39	Teva Investigational Site 13204	Saint Louis	Missouri	United States	63143
40	Teva Investigational Site 13258	Boys Town	Nebraska	United States	68010
41	Teva Investigational Site 13769	Belleville	New Jersey	United States	07109
42	Teva Investigational Site 13210	Ocean City	New Jersey	United States	07712
43	Teva Investigational Site 13188	New Hyde Park	New York	United States	11040
44	Teva Investigational Site 13232	New York	New York	United States	10016
45	Teva Investigational Site 13767	New York	New York	United States	11570
46	Teva Investigational Site 13186	Cincinnati	Ohio	United States	45267
47	Teva Investigational Site 13253	Cleveland	Ohio	United States	44106
48	Teva Investigational Site 13240	Toledo	Ohio	United States	43606
49	Teva Investigational Site 13259	Edmond	Oklahoma	United States	73034
50	Teva Investigational Site 13238	Oklahoma City	Oklahoma	United States	73112
51	Teva Investigational Site 13195	Medford	Oregon	United States	97504
52	Teva Investigational Site 13242	Bethlehem	Pennsylvania	United States	18020
53	Teva Investigational Site 13218	Jenkintown	Pennsylvania	United States	19046
54	Teva Investigational Site 13189	Philadelphia	Pennsylvania	United States	19107
55	Teva Investigational Site 13190	Pittsburgh	Pennsylvania	United States	15241
56	Teva Investigational Site 13209	East Providence	Rhode Island	United States	?02914
57	Teva Investigational Site 13217	Lincoln	Rhode Island	United States	02865
58	Teva Investigational Site 13223	Knoxville	Tennessee	United States	37919
59	Teva Investigational Site 13185	Arlington	Texas	United States	76018
60	Teva Investigational Site 13199	Corsicana	Texas	United States	75110
61	Teva Investigational Site 13260	Dallas	Texas	United States	75225
62	Teva Investigational Site 13224	San Antonio	Texas	United States	78229
63	Teva Investigational Site 13184	Waco	Texas	United States	76712
64	Teva Investigational Site 13187	Provo	Utah	United States	84604
65	Teva Investigational Site 13207	Abingdon	Virginia	United States	24210
66	Teva Investigational Site 13183	Fairfax	Virginia	United States	22030
67	Teva Investigational Site 13257	Falls Church	Virginia	United States	22044
68	Teva Investigational Site 13239	Richmond	Virginia	United States	23233
69	Teva Investigational Site 13227	Spokane	Washington	United States	99204
70	Teva Investigational Site 20040	Buenos Aires		Argentina	C1122AAK
71	Teva Investigational Site 20033	Buenos Aires		Argentina	C1426ABP
72	Teva Investigational Site 20035	Buenos Aires		Argentina
73	Teva Investigational Site 20041	Cordoba		Argentina	X5003DCE
74	Teva Investigational Site 20053	Lanus		Argentina	B1824 KAJ
75	Teva Investigational Site 20037	Mar Del Plata		Argentina	CP 7600
76	Teva Investigational Site 20036	Mendoza		Argentina	5500
77	Teva Investigational Site 20054	Rosario		Argentina	2000
78	Teva Investigational Site 20032	Rosario		Argentina	S2000DBS
79	Teva Investigational Site 20046	San Miguel de Tucuman		Argentina	T4000CHE
80	Teva Investigational Site 20045	San Rafael		Argentina	5600
81	Teva Investigational Site 78085	Bedford Park		Australia	5042
82	Teva Investigational Site 78083	Nedlands		Australia	6009
83	Teva Investigational Site 78088	Parkville		Australia	3052
84	Teva Investigational Site 78087	Sherwood		Australia	4075
85	Teva Investigational Site 78084	Woolloongabba		Australia
86	Teva Investigational Site 37054	Bruxelles		Belgium	1200
87	Teva Investigational Site 37053	Erpent		Belgium	5101
88	Teva Investigational Site 37055	Gent		Belgium	9000
89	Teva Investigational Site 11106	Vancouver	British Columbia	Canada	V5Z 4E1
90	Teva Investigational Site 11105	Etobicoke	Ontario	Canada	M9V 4B4
91	Teva Investigational Site 11109	Windsor		Canada	N8X 5A6
92	Teva Investigational Site 54130	Jablonec nad Nisou		Czechia	46601
93	Teva Investigational Site 54128	Jindrichuv Hradec		Czechia	377 01
94	Teva Investigational Site 54129	Tabor		Czechia	39001
95	Teva Investigational Site 35182	Strasbourg		France	67091
96	Teva Investigational Site 35183	Toulouse		France	31000
97	Teva Investigational Site 32559	Bad Worishofen		Germany	86825
98	Teva Investigational Site 32556	Berlin		Germany	10717
99	Teva Investigational Site 32561	Berlin		Germany	10969
100	Teva Investigational Site 32570	Berlin		Germany	12159
101	Teva Investigational Site 32567	Berlin		Germany	13507
102	Teva Investigational Site 32564	Berlin		Germany	14059
103	Teva Investigational Site 32560	Frankfurt am Main		Germany	60596
104	Teva Investigational Site 32568	Frankfurt		Germany	60389
105	Teva Investigational Site 32562	Hamburg		Germany	22299
106	Teva Investigational Site 32566	Hannover		Germany	30173
107	Teva Investigational Site 32555	Koblenz		Germany	56068
108	Teva Investigational Site 32563	Leipzig		Germany	04357
109	Teva Investigational Site 32557	Leipzig		Germany	4275
110	Teva Investigational Site 32565	Lubeck		Germany	23552
111	Teva Investigational Site 32551	Mainz		Germany	55131
112	Teva Investigational Site 32569	Witten		Germany	58452
113	Teva Investigational Site 51216	Balassagyarmat		Hungary	2660
114	Teva Investigational Site 51228	Budapest		Hungary	H-1036
115	Teva Investigational Site 51221	Csorna		Hungary	9300
116	Teva Investigational Site 51220	Debrecen		Hungary	4032
117	Teva Investigational Site 51223	Debrecen		Hungary	4032
118	Teva Investigational Site 51255	Dombovar		Hungary	7200
119	Teva Investigational Site 51218	Godollo		Hungary	2100
120	Teva Investigational Site 51222	Gyor		Hungary	9023
121	Teva Investigational Site 51227	Hajdunanas		Hungary	4080
122	Teva Investigational Site 51226	Kaposvar		Hungary	7400
123	Teva Investigational Site 51231	Kapuvar		Hungary	9330
124	Teva Investigational Site 51224	Szazhalombatta		Hungary	2440
125	Teva Investigational Site 51219	Szeged		Hungary	6725
126	Teva Investigational Site 51225	Szigetvar		Hungary	7900
127	Teva Investigational Site 51217	Szombathely		Hungary
128	Teva Investigational Site 51229	Veszprem		Hungary	8200
129	Teva Investigational Site 80077	Ashkelon		Israel	7830604
130	Teva Investigational Site 80076	Haifa		Israel	3436212
131	Teva Investigational Site 80094	Jerusalem		Israel	91031
132	Teva Investigational Site 80078	Jerusalem		Israel	91120
133	Teva Investigational Site 80080	Kfar Saba		Israel	44281
134	Teva Investigational Site 80073	Petach Tikva		Israel	49100
135	Teva Investigational Site 80081	Petah Tikva		Israel	49100
136	Teva Investigational Site 80079	Ramat Gan		Israel	5262160
137	Teva Investigational Site 80075	Rehovot		Israel	76100
138	Teva Investigational Site 84039	Amagasaki		Japan	660-8550
139	Teva Investigational Site 84053	Ginowan		Japan	901-2214
140	Teva Investigational Site 84049	Hakodate		Japan	?040-8611
141	Teva Investigational Site 84034	Hiroshima		Japan	734-8530
142	Teva Investigational Site 84036	Kanazawa-shi		Japan	920-8530
143	Teva Investigational Site 84037	Kishiwada-shi		Japan	596-8501
144	Teva Investigational Site 84048	Kobe		Japan	651-0073
145	Teva Investigational Site 84044	Kobe		Japan	651-2273
146	Teva Investigational Site 84047	Kodaira		Japan	187-8510
147	Teva Investigational Site 84045	Kumamoto		Japan	862-0965
148	Teva Investigational Site 84043	Mizunami-shi		Japan	509-6134
149	Teva Investigational Site 84041	Sagamihara		Japan	252-5188
150	Teva Investigational Site 84031	Tokyo		Japan	103-0027
151	Teva Investigational Site 84032	Tokyo		Japan	103-0027
152	Teva Investigational Site 84038	Toyama-shi		Japan	930-0194
153	Teva Investigational Site 84046	Toyama		Japan	930-8550
154	Teva Investigational Site 84035	Toyoake-shi		Japan	470-1192
155	Teva Investigational Site 84040	Yokohama-shi		Japan	231-8682
156	Teva Investigational Site 87015	Bucheon		Korea, Republic of	420-767
157	Teva Investigational Site 87016	Seoul		Korea, Republic of	152-703
158	Teva Investigational Site 87014	Seoul		Korea, Republic of	152703
159	Teva Investigational Site 21084	Guadalajara		Mexico	44100
160	Teva Investigational Site 21085	Guadalajara		Mexico	44130
161	Teva Investigational Site 21088	Guadalajara		Mexico	44160
162	Teva Investigational Site 21089	Guadalajara		Mexico	44220
163	Teva Investigational Site 21087	Monterrey		Mexico	64718
164	Teva Investigational Site 21086	Zapopan		Mexico	45070
165	Teva Investigational Site 79047	Auckland		New Zealand	1640
166	Teva Investigational Site 79046	Auckland		New Zealand
167	Teva Investigational Site 53310	Bialystok		Poland	15-044
168	Teva Investigational Site 53315	Bialystok		Poland	15-276
169	Teva Investigational Site 53308	Gdansk		Poland	80-952
170	Teva Investigational Site 53311	Krakow		Poland	31-624
171	Teva Investigational Site 53314	Lodz		Poland	90-153
172	Teva Investigational Site 53312	Lodz		Poland	90-329
173	Teva Investigational Site 53313	Poznan		Poland	60-214
174	Teva Investigational Site 53309	Tarnow		Poland	33-100
175	Teva Investigational Site 52108	Brasov		Romania	500051
176	Teva Investigational Site 52109	Brasov		Romania	500086
177	Teva Investigational Site 52107	Bucharest		Romania	11461
178	Teva Investigational Site 52105	Bucharest		Romania	50159
179	Teva Investigational Site 52104	Cluj-Napoca		Romania	400371
180	Teva Investigational Site 52111	Deva		Romania
181	Teva Investigational Site 52106	Targu Mures		Romania	540136
182	Teva Investigational Site 52110	Timisoara		Romania	300310
183	Teva Investigational Site 50350	Barnaul		Russian Federation	656024
184	Teva Investigational Site 50354	Kemerovo		Russian Federation	650099
185	Teva Investigational Site 50348	Moscow		Russian Federation	115478
186	Teva Investigational Site 50351	Moscow		Russian Federation	119991
187	Teva Investigational Site 50347	Novosibirsk		Russian Federation	630091
188	Teva Investigational Site 50355	Saint Petersburg		Russian Federation	194356
189	Teva Investigational Site 50352	St. Petersburg		Russian Federation	197089
190	Teva Investigational Site 50349	Tomsk		Russian Federation	634063
191	Teva Investigational Site 90027	Benoni		South Africa	1500
192	Teva Investigational Site 90028	Bloemfontein		South Africa	9301
193	Teva Investigational Site 90026	Cape Town		South Africa	7505
194	Teva Investigational Site 90031	Cape Town		South Africa	7570
195	Teva Investigational Site 90029	Cape Town		South Africa	7937
196	Teva Investigational Site 90032	Durban		South Africa	4091
197	Teva Investigational Site 90030	Durban		South Africa	4170
198	Teva Investigational Site 31149	Barcelona		Spain	08025
199	Teva Investigational Site 31147	Esplugues de Llobregat		Spain	08950
200	Teva Investigational Site 31152	Girona		Spain	17005
201	Teva Investigational Site 31154	Vitoria-Gasteiz		Spain	01009
202	Teva Investigational Site 82042	Ankara		Turkey	06290
203	Teva Investigational Site 82041	Izmir		Turkey	35120
204	Teva Investigational Site 82040	Kocaeli		Turkey	41380
205	Teva Investigational Site 82039	Konya		Turkey
206	Teva Investigational Site 82043	Mersin		Turkey	33169
207	Teva Investigational Site 58216	Chernivtsi		Ukraine	58023
208	Teva Investigational Site 58219	Dnipropetrovsk		Ukraine	49074
209	Teva Investigational Site 58225	Dnipropetrovsk		Ukraine	49101
210	Teva Investigational Site 58222	Ivano-Frankivsk		Ukraine	76018
211	Teva Investigational Site 58227	Kharkiv		Ukraine	61002
212	Teva Investigational Site 58213	Kharkiv		Ukraine	61007
213	Teva Investigational Site 58221	Kharkiv		Ukraine	61035
214	Teva Investigational Site 58223	Kharkiv		Ukraine	61039
215	Teva Investigational Site 58214	Kremenchuk		Ukraine	39617
216	Teva Investigational Site 58228	Kryvyi Rih		Ukraine	50082
217	Teva Investigational Site 58220	Kyiv		Ukraine	03680
218	Teva Investigational Site 58230	Kyiv		Ukraine	04050
219	Teva Investigational Site 58218	Kyiv		Ukraine	04107
220	Teva Investigational Site 58226	Kyiv		Ukraine	04201
221	Teva Investigational Site 58253	Kyiv		Ukraine	?03680
222	Teva Investigational Site 58234	Sumy		Ukraine	40022
223	Teva Investigational Site 58233	Vinnytsia		Ukraine	21001
224	Teva Investigational Site 58229	Vinnytsya		Ukraine	21001
225	Teva Investigational Site 58231	Zaporizhzhya		Ukraine	69063
226	Teva Investigational Site 58224	Zhaporizhzhya		Ukraine	69035

Sponsors and Collaborators

• Teva Branded Pharmaceutical Products R&D, Inc.
• PPD

Investigators

• Study Director: Teva Medical Expert, MD, Teva Branded Pharmaceutical Products R&D, Inc.

Study Documents (Full-Text)

• Study Protocol - Oct 24, 2016
• Statistical Analysis Plan - May 1, 2017

More Information

Publications

None provided.

• Responsible Party: Teva Branded Pharmaceutical Products R&D, Inc.
• ClinicalTrials.gov Identifier: NCT02452190
• Other Study ID Numbers: C38072-AS-30025; 2015-000865-29
• First Posted: May 22, 2015
• Last Update Posted: Nov 9, 2021
• Last Verified: Nov 1, 2021

• Additional relevant MeSH terms: Asthma; Reslizumab

Study Results

Participant Flow

Pre-assignment Detail	A total of 1159 participants were screened, of whom 468 participants were eligible and enrolled in a 3-week run-in period for self-monitoring. All 468 enrolled participants were then randomized at 201 centers in 20 countries.

Arm/Group Title	Placebo	Reslizumab 110 mg
Arm/Group Description	Matching placebo administered subcutaneously once every 4 weeks (+/-7 days) for a total of 13 doses.	Reslizumab 110 milligrams (mg) administered subcutaneously once every 4 weeks (+/-7 days) for a total of 13 doses.
Period Title: Overall Study
STARTED	232	236
Intent to Treat (ITT) Population	230	234
Safety Population	231	237
COMPLETED	197	212
NOT COMPLETED	35	24

Baseline Characteristics

Arm/Group Title	Placebo	Reslizumab 110 mg	Total
Arm/Group Description	Matching placebo administered subcutaneously once every 4 weeks (+/-7 days) for a total of 13 doses.	Reslizumab 110 milligrams (mg) administered subcutaneously once every 4 weeks (+/-7 days) for a total of 13 doses.	Total of all reporting groups
Overall Participants	230	234	464
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	44.8 (17.70)	46.9 (17.63)	45.9 (17.68)
Sex: Female, Male (Count of Participants)
Female	128 55.7%	144 61.5%	272 58.6%
Male	102 44.3%	90 38.5%	192 41.4%
Race/Ethnicity, Customized (Number) [Number]
Not Hispanic or Latino	201 87.4%	216 92.3%	417 89.9%
Hispanic or Latino	26 11.3%	17 7.3%	43 9.3%
Unknown	3 1.3%	1 0.4%	4 0.9%
Race/Ethnicity, Customized (Number) [Number]
White	199 86.5%	205 87.6%	404 87.1%
Black or African American	11 4.8%	15 6.4%	26 5.6%
Asian	11 4.8%	6 2.6%	17 3.7%
American Indian or Alaska Native	1 0.4%	0 0%	1 0.2%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Other	8 3.5%	8 3.4%	16 3.4%
Region of Enrollment (Count of Participants)
United States and Canada	58 25.2%	52 22.2%	110 23.7%
Europe	125 54.3%	135 57.7%	260 56%
Rest of World	47 20.4%	47 20.1%	94 20.3%
Pre-bronchodilator Forced Expiratory Volume in 1 Second (FEV1) (liters) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [liters]	2.102 (0.870)	1.988 (0.780)	2.044 (0.827)
Asthma Quality of Life Questionnaire for Participants 12 Years and Older (AQLQ+12) Score (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	4.39 (0.995)	4.28 (1.048)	4.33 (1.022)
Asthma Control Questionnaire (ACQ-6) Score (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	2.42 (0.812)	2.48 (0.88)	2.45 (0.847)
Total Asthma Symptom Scores (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	2.6 (1.62)	2.5 (1.53)	2.57 (1.578)
Blood Eosinophil Category at Baseline (Count of Participants)
less than (<)300 per (/) microliter (µL)	0 0%	1 0.4%	1 0.2%
300 to <400/µL	42 18.3%	48 20.5%	90 19.4%
greater than or equal to (≥)400/µL	188 81.7%	185 79.1%	373 80.4%
Number of Clinical Asthma Exacerbation (CAE) Events in the Previous 12 Months (Count of Events) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Count of Events]	2.30 (0.843)	2.35 (1.043)	2.33 (0.949)

Outcome Measures

1. Primary Outcome

Title	Number of Clinical Asthma Exacerbations (CAEs) During 52 Weeks of Treatment
Description	A CAE was defined as a clinically-judged deterioration in asthma control, as determined by the investigator and as evidenced by new or worsening asthma signs or symptoms based on the participant's history, asthma control diary, physical examination, and/or ambulatory or clinic visit assessment of lung function and that resulted in a medical intervention, including at least 1 of the following: 1) use of systemic corticosteroids (oral or injection) or at least a doubling from a stable maintenance oral corticosteroid dose for at least 3 days; 2) asthma-specific hospital admission; 3) asthma-specific emergency department visit. Adjusted CAE rate and confidence intervals were based on Negative Binomial regression model adjusted for stratification factors. Results are presented as adjusted means. For this analysis, the offset variable is calculated as the logarithm of treatment duration minus the summed duration of exacerbations during the treatment period.
Time Frame	Day 1 to Week 52

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants, excluding participants from the site terminated due to GCP issues. Treatment was based on the treatment to which participants were randomized, regardless of which treatment they received.

Arm/Group Title	Placebo	Reslizumab 110 mg
Arm/Group Description	Matching placebo administered subcutaneously once every 4 weeks (+/-7 days) for a total of 13 doses.	Reslizumab 110 milligrams (mg) administered subcutaneously once every 4 weeks (+/-7 days) for a total of 13 doses.
Measure Participants	230	234
Mean (95% Confidence Interval) [events]	0.52	0.41

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Reslizumab 110 mg
	Comments	The frequency of CAEs was analyzed using the generalized linear model (GLM) for data from the negative binomial distributions that is commonly referred to as the negative binomial (NB) regression model. The primary NB model included the treatment group, randomization stratification factors, and number of prior exacerbations as model factors and the logarithm of treatment duration excluding the summed duration of exacerbations in the treatment period as an offset variable.
	Type of Statistical Test	Superiority
	Comments	A fixed-sequence multiple testing procedure was implemented to test the primary and secondary endpoints while controlling the overall Type I error rate at 0.05. At the point where p>0.05, no further comparisons were interpreted inferentially.
Statistical Test of Hypothesis	p-Value	0.194
	Comments	The treatment effect was tested using the likelihood based Chi-square test at the 0.05 significance level.
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	CAE rate ratio (reslizumab vs placebo)
	Estimated Value	0.79
	Confidence Interval	(2-Sided) 95%; 0.562 to 1.124
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Change From Baseline to Week 52 in Pre-bronchodilator Forced Expiratory Volume in 1 Second (FEV1)
Description	Change in pre-bronchodilator FEV1 from baseline to week 52 is presented. FEV1 is a standard measurement of air movement in the lungs of participants with asthma obtained from pulmonary function tests. It is the volume of air expired in the first second of a forced expiration using a spirometer. Analysis of the change from baseline to each visit was performed using a mixed effect model for repeated measures (MMRM) including fixed effects for treatment, visit, treatment by visit interaction, age group, blood eosinophil counts at enrollment, and sex, height and baseline value as covariates, and participant as a random effect.
Time Frame	Baseline, Week 52

Outcome Measure Data

Analysis Population Description

ITT includes all randomized participants, excluding participants from the site terminated due to GCP issues. Treatment was based on the treatment to which participants were randomized, regardless of which treatment they received. Overall number of participants analyzed=participants with both baseline and Week 52 FEV1 values available.

Arm/Group Title	Placebo	Reslizumab 110 mg
Arm/Group Description	Matching placebo administered subcutaneously once every 4 weeks (+/-7 days) for a total of 13 doses.	Reslizumab 110 milligrams (mg) administered subcutaneously once every 4 weeks (+/-7 days) for a total of 13 doses.
Measure Participants	193	211
Least Squares Mean (Standard Error) [liters]	0.225 (0.040)	0.368 (0.039)

3. Secondary Outcome

Title	Change From Baseline to Week 52 in Asthma Quality of Life Questionnaire for Participants 12 Years and Older (AQLQ+12) Score
Description	AQLQ is a 32-item instrument administered as a self-assessment. AQLQ+12 is a modified version of AQLQ developed to measure functional impairments of participants aged 12-70 years. It is divided into 4 domains: activity limitation, symptoms, emotional function, and environmental stimuli. Participants were asked to recall their experiences during the last 2 weeks and respond to each question on a 7-point scale (1=severe impairment, 7=no impairment), where higher scores indicated "better quality of life." Overall AQLQ+12 score is the mean of all 32 responses. Analysis of the change from baseline to each visit was performed using a MMRM including fixed effects for treatment, visit, treatment by visit interaction, age group, blood eosinophil counts at enrollment, and sex, height and baseline value as covariates, and participant as a random effect.
Time Frame	Baseline, Week 52

Outcome Measure Data

Analysis Population Description

Participants of the ITT population aged 12 to 70 years. Overall number of participants analyzed=participants with both baseline and Week 52 AQLQ+12 score available.

Arm/Group Title	Placebo	Reslizumab 110 mg
Arm/Group Description	Matching placebo administered subcutaneously once every 4 weeks (+/-7 days) for a total of 13 doses.	Reslizumab 110 milligrams (mg) administered subcutaneously once every 4 weeks (+/-7 days) for a total of 13 doses.
Measure Participants	188	197
Least Squares Mean (Standard Error) [units on a scale]	1.06 (0.089)	1.14 (0.087)

4. Secondary Outcome

Title	Change From Baseline to Week 52 in 6-item Asthma Control Questionnaire (ACQ-6) Score
Description	The ACQ-6 is a 6-item validated asthma assessment tool that has been widely used. Six questions are self-assessments (completed by the participant), 5 questions assessing asthma symptoms: night-time waking, symptoms on waking, activity limitation, shortness of breath, wheezing, and 1 question for short-acting bronchodilator use. Each item on the ACQ-6 has a possible score ranges from 0 to 6, and the total score is the mean of all responses. The total score ranging from 0-6 (0=totally controlled and 6=severely uncontrolled). A higher score indicated poorer asthma control. Analysis of the change from baseline to each visit was performed using a mixed effect model for repeated measures (MMRM) including fixed effects for treatment, visit, treatment by visit interaction, age group, blood eosinophil counts at enrollment, and sex, height and baseline value as covariates, and participant as a random effect.
Time Frame	Baseline, Week 52

Outcome Measure Data

Analysis Population Description

ITT population includes all randomized participants, excluding those from the site terminated due to GCP issues. Treatment was based on the treatment to which participants were randomized, regardless of which treatment they received. Overall number of participants analyzed=participants with both baseline and Week 52 ACQ-6 score available.

Arm/Group Title	Placebo	Reslizumab 110 mg
Arm/Group Description	Matching placebo administered subcutaneously once every 4 weeks (+/-7 days) for a total of 13 doses.	Reslizumab 110 milligrams (mg) administered subcutaneously once every 4 weeks (+/-7 days) for a total of 13 doses.
Measure Participants	197	212
Least Squares Mean (Standard Error) [units on a scale]	-1.14 (0.080)	-1.22 (0.078)

5. Secondary Outcome

Title	Change From Baseline to Week 52 in Total Asthma Symptom Scores (Day and Night)
Description	Asthma symptoms were recorded by participant each day and night in an asthma control diary. Night score was assessed on a 5-point scale where 0=no symptoms, slept through night, to 4=bad night, no sleep. Day score was assessed on a 6-point scale where 0=very well, no symptoms, to 5= asthma very severe, unable to carry out daily activities. Total asthma symptom score was calculated by taking the sum of the night and day asthma symptom scores recorded, ranging from 0 (no symptom) to 9 (severe symptom). A lower symptom score indicated a better outcome. Analysis of the change from baseline to each visit was performed using a MMRM including fixed effects for treatment, visit, treatment by visit interaction, age group, blood eosinophil counts at enrollment, and sex, height and baseline value as covariates, and participant as a random effect.
Time Frame	Baseline, Week 52

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants, excluding participants from site terminated due to GCP issues. Treatment was based on treatment to which participants were randomized, regardless of which treatment they received. Overall number of participants analyzed=participants with both baseline and Week 52 total asthma symptom score.

Arm/Group Title	Placebo	Reslizumab 110 mg
Arm/Group Description	Matching placebo administered subcutaneously once every 4 weeks (+/-7 days) for a total of 13 doses.	Reslizumab 110 milligrams (mg) administered subcutaneously once every 4 weeks (+/-7 days) for a total of 13 doses.
Measure Participants	128	143
Least Squares Mean (Standard Error) [units on a scale]	-1.4 (0.12)	-1.5 (0.12)

6. Secondary Outcome

Title	Percentage of Asthma Control Days
Description	The percentage of asthma control days over 52 weeks of treatment is presented. An asthma control day was defined as a day on which the participant used less than or equal to 2 puffs of inhaled short-acting beta-agonist, had no nighttime awakenings, and experienced no asthma exacerbations. Analysis of the change from baseline to each visit was performed using a mixed effect MMRM including fixed effects for treatment, visit, treatment by visit interaction, age group, blood eosinophil counts at enrollment, and sex, height and baseline value as covariates, and participant as a random effect.
Time Frame	Day 1 to Week 52

Outcome Measure Data

Analysis Population Description

ITT population includes all randomized participants, excluding participants from the site terminated due to GCP issues. Treatment was based on the treatment to which participants were randomized, regardless of which treatment they actually received.

Arm/Group Title	Placebo	Reslizumab 110 mg
Arm/Group Description	Matching placebo administered subcutaneously once every 4 weeks (+/-7 days) for a total of 13 doses.	Reslizumab 110 milligrams (mg) administered subcutaneously once every 4 weeks (+/-7 days) for a total of 13 doses.
Measure Participants	230	234
Least Squares Mean (Standard Error) [percentage of days]	7.1 (1.27)	8.0 (1.24)

7. Secondary Outcome

Title	Change From Baseline to Week 32 in St. George's Respiratory Questionnaire (SGRQ) Total Score
Description	The SGRQ is a 17-item questionnaire with 50 weighted responses. It provides a total score and three component scores: Symptoms (distress caused by respiratory symptoms), Activity (physical activities that cause or are limited by breathlessness), and Impacts (social and psychological effects of the disease). The total score and each of the SGRQ subscores are scored from 0 to 100 where 0 indicates best and 100 indicates worst health. An increase in score indicates worsening health. Analysis of the change from baseline to each visit was performed using a mixed effect model for repeated measures (MMRM) including fixed effects for treatment, visit, treatment by visit interaction, age group, blood eosinophil counts at enrollment, and sex, height and baseline value as covariates, and participant as a random effect.
Time Frame	Baseline, Week 32

Outcome Measure Data

Analysis Population Description

ITT population includes all randomized participants, excluding participants from site terminated due to GCP issues. Treatment was based on treatment to which participants were randomized, regardless of which treatment they received. Overall number of participants analyzed= participants with both baseline and Week 32 SGRQ total scores available.

Arm/Group Title	Placebo	Reslizumab 110 mg
Arm/Group Description	Matching placebo administered subcutaneously once every 4 weeks (+/-7 days) for a total of 13 doses.	Reslizumab 110 milligrams (mg) administered subcutaneously once every 4 weeks (+/-7 days) for a total of 13 doses.
Measure Participants	199	222
Least Squares Mean (Standard Error) [units on a scale]	-13.1 (1.38)	-16.4 (1.32)

8. Secondary Outcome

Title	Kaplan-Meier (K-M) Estimate of Probability (Percent [%]) of Not Experiencing a CAE by Week 52
Description	CAE was defined as a clinically judged deterioration in asthma control, as determined by the investigator and as evidenced by new or worsening asthma signs or symptoms based on the participant's history, asthma control diary, physical examination, and/or ambulatory or clinic visit assessment of lung function and that resulted in a medical intervention, including at least 1 of the following: 1) use of systemic corticosteroids (oral or injection) or at least a doubling from a stable maintenance oral corticosteroid dose for at least 3 days; 2) asthma-specific hospital admission; 3) asthma-specific emergency department visit. The KM method was used to estimate and compare the distributions of time to first CAE between treatment groups. Participants without an event during the treatment period were censored at either the date of the end of treatment (Week 52) visit for participants who completed treatment or at the date of last dose (+4 weeks) for participants who discontinued early.
Time Frame	Day 1 to Week 52

Outcome Measure Data

Analysis Population Description

ITT population includes all randomized participants, excluding participants from the site terminated due to GCP issues. Treatment was based on the treatment to which participants were randomized, regardless of which treatment they received.

Arm/Group Title	Placebo	Reslizumab 110 mg
Arm/Group Description	Matching placebo administered subcutaneously once every 4 weeks (+/-7 days) for a total of 13 doses.	Reslizumab 110 milligrams (mg) administered subcutaneously once every 4 weeks (+/-7 days) for a total of 13 doses.
Measure Participants	230	234
Number (95% Confidence Interval) [percent probability]	0.66	0.66

9. Secondary Outcome

Title	Number of CAEs Requiring Hospitalization and/or Emergency Department Visits During 52 Weeks of Treatment
Description	A CAE was defined as a clinically judged deterioration in asthma control, as determined by the investigator and as evidenced by new or worsening asthma signs or symptoms based on the participant's history, asthma control diary, physical examination, and/or ambulatory or clinic visit assessment of lung function and that resulted in a medical intervention, including at least 1 of the following: 1) use of systemic corticosteroids (oral or injection) or at least a doubling from a stable maintenance oral corticosteroid dose for at least 3 days; 2) asthma-specific hospital admission; 3) asthma-specific emergency department visit. The frequency of CAEs over 52-week treatment period is expressed as adjusted CAEs rate in 52 weeks. Adjusted CAE rate and confidence intervals were based on Negative Binomial regression model adjusted for stratification factors (age group, blood eosinophil group) and number of prior exacerbations, and an offset variable.
Time Frame	Day 1 to Week 52

Outcome Measure Data

Analysis Population Description

ITT population includes all randomized participants, excluding participants from the site terminated due to GCP issues. Treatment was based on the treatment to which participants were randomized, regardless of which treatment they received.

Arm/Group Title	Placebo	Reslizumab 110 mg
Arm/Group Description	Matching placebo administered subcutaneously once every 4 weeks (+/-7 days) for a total of 13 doses.	Reslizumab 110 milligrams (mg) administered subcutaneously once every 4 weeks (+/-7 days) for a total of 13 doses.
Measure Participants	230	234
Mean (95% Confidence Interval) [events]	0.05	0.05

10. Secondary Outcome

Title	Number of Moderate Exacerbations During 52 Weeks of Treatment
Description	A moderate exacerbation was defined as a clinically judged deterioration in asthma control as determined by investigator and as evidenced by new or worsening asthma signs or symptoms based on the participant's history, asthma control diary, physical examination, and/or ambulatory or clinic visit assessment of lung function and that resulted in a medical intervention requiring additional asthma controller medication that was not a systemic corticosteroid and did not result in an asthma-specific hospitalization or emergency department visit (that is, a medical intervention that did not otherwise meet the criteria for primary endpoint). Frequency of moderate exacerbations over 52-week treatment period is expressed as adjusted exacerbation rate in 52 weeks. Adjusted exacerbation rate and confidence intervals were based on Negative Binomial regression model adjusted for stratification factors (age group, blood eosinophil group) and number of prior exacerbations, and an offset variable.
Time Frame	Day 1 to Week 52

Outcome Measure Data

Analysis Population Description

ITT population includes all randomized participants, excluding participants from the site terminated due to GCP issues. Treatment was based on the treatment to which participants were randomized, regardless of which treatment they received.

Arm/Group Title	Placebo	Reslizumab 110 mg
Arm/Group Description	Matching placebo administered subcutaneously once every 4 weeks (+/-7 days) for a total of 13 doses.	Reslizumab 110 milligrams (mg) administered subcutaneously once every 4 weeks (+/-7 days) for a total of 13 doses.
Measure Participants	230	234
Mean (95% Confidence Interval) [events]	0.15	0.14

Adverse Events

Time Frame	From the first dose of study drug to the end of treatment visit (Week 52) for completed participants and between the first dose of study drug and 4 weeks after the last dose of study drug for participants who discontinued treatment early. Safety population includes all participants who received at least 1 dose of study drug (including from the site terminated due to GCP issues).
Adverse Event Reporting Description	1 participant randomized to the placebo group was treated with reslizumab 110 mg at 1 study visit and counted in the reslizumab 110 mg arm for safety.There were no deaths during the treatment period. 1 death in the reslizumab group occurred 48 days after the participant's last dose.This participant's reason for discontinued was coded as death by the study site; but, the participant is not counted in all-cause mortality as the death occurred after the treatment period concluded.
Arm/Group Title	Placebo		Reslizumab 110 mg
Arm/Group Description	Matching placebo administered subcutaneously once every 4 weeks (+/-7 days) for a total of 13 doses.		Reslizumab 110 milligrams (mg) administered subcutaneously once every 4 weeks (+/-7 days) for a total of 13 doses.
All Cause Mortality
	Placebo		Reslizumab 110 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/231 (0%)		0/237 (0%)
Serious Adverse Events
	Placebo		Reslizumab 110 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	19/231 (8.2%)		19/237 (8%)
Cardiac disorders
Angina unstable	1/231 (0.4%)	1	1/237 (0.4%)	1
Gastrointestinal disorders
Abdominal hernia	1/231 (0.4%)	1	0/237 (0%)	0
Abdominal pain	0/231 (0%)	0	1/237 (0.4%)	1
Gastrointestinal disorder	0/231 (0%)	0	1/237 (0.4%)	1
Hepatobiliary disorders
Biliary cirrhosis primary	0/231 (0%)	0	1/237 (0.4%)	1
Cholelithiasis	4/231 (1.7%)	4	0/237 (0%)	0
Immune system disorders
Anaphylactic reaction	1/231 (0.4%)	1	0/237 (0%)	0
Reaction to food colouring	1/231 (0.4%)	1	0/237 (0%)	0
Infections and infestations
Appendicitis	0/231 (0%)	0	1/237 (0.4%)	1
Cholecystitis infective	0/231 (0%)	0	1/237 (0.4%)	1
Chronic sinusitis	1/231 (0.4%)	1	1/237 (0.4%)	1
Otitis externa	0/231 (0%)	0	1/237 (0.4%)	1
Pneumonia	4/231 (1.7%)	4	2/237 (0.8%)	2
Pyelonephritis	1/231 (0.4%)	1	0/237 (0%)	0
Respiratory tract infection	0/231 (0%)	0	1/237 (0.4%)	1
Metabolism and nutrition disorders
Dehydration	1/231 (0.4%)	1	0/237 (0%)	0
Musculoskeletal and connective tissue disorders
Rhabdomyolysis	0/231 (0%)	0	1/237 (0.4%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Benign tracheal neoplasm	0/231 (0%)	0	1/237 (0.4%)	1
Bronchial neoplasm benign	0/231 (0%)	0	1/237 (0.4%)	1
Rectal adenocarcinoma	0/231 (0%)	0	1/237 (0.4%)	1
Nervous system disorders
Lumbar radiculopathy	0/231 (0%)	0	1/237 (0.4%)	1
Syncope	1/231 (0.4%)	1	0/237 (0%)	0
Renal and urinary disorders
Acute kidney injury	1/231 (0.4%)	1	0/237 (0%)	0
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure	1/231 (0.4%)	1	0/237 (0%)	0
Asthma	5/231 (2.2%)	5	4/237 (1.7%)	5
Dyspnoea	0/231 (0%)	0	1/237 (0.4%)	1
Eosinophilic pneumonia	1/231 (0.4%)	1	0/237 (0%)	0
Nasal polyps	1/231 (0.4%)	1	1/237 (0.4%)	1
Pulmonary embolism	0/231 (0%)	0	1/237 (0.4%)	1
Sinusitis noninfective	1/231 (0.4%)	1	0/237 (0%)	0
Vascular disorders
Hypertensive crisis	0/231 (0%)	0	1/237 (0.4%)	1
Other (Not Including Serious) Adverse Events
	Placebo		Reslizumab 110 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	97/231 (42%)		102/237 (43%)
General disorders
Injection site erythema	7/231 (3%)	13	13/237 (5.5%)	35
Infections and infestations
Acute sinusitis	15/231 (6.5%)	19	14/237 (5.9%)	16
Bronchitis	17/231 (7.4%)	23	13/237 (5.5%)	14
Upper respiratory tract infection	19/231 (8.2%)	26	28/237 (11.8%)	37
Viral upper respiratory tract infection	31/231 (13.4%)	42	27/237 (11.4%)	45
Nervous system disorders
Headache	10/231 (4.3%)	19	14/237 (5.9%)	28
Respiratory, thoracic and mediastinal disorders
Asthma	18/231 (7.8%)	25	9/237 (3.8%)	15
Rhinitis allergic	12/231 (5.2%)	12	16/237 (6.8%)	16

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Sponsor has the right 60 days before submission for publication to review/provide comments. If the Sponsor's review shows that potentially patentable subject matter would be disclosed, publication or public disclosure shall be delayed for up to 90 additional days in order for the Sponsor, or Sponsor's designees, to file the necessary patent applications. In multicenter trials, each PI will postpone single center publications until after disclosure or publication of multicenter data.