A Study to Evaluate the Safety of MEDI8897 for the Prevention of Medically Attended Respiratory Syncytial Virus(RSV) Lower Respiratory Track Infection (LRTI) in High-risk Children

Sponsor

AstraZeneca (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT03959488

Collaborator

(none)

925

Enrollment

128

Locations

Arms

39.8

Anticipated Duration (Months)

7.2

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the safety and tolerability of MEDI8897 compared to palivizumab when administered to preterm infants entering their first RSV season and children with chronic lung disease (CLD) and congenital heart disease (CHD) entering their first and second RSV season.

Condition or Disease	Intervention/Treatment	Phase
Respiratory Syncytial Virus Infections	Drug: MEDI8897 Drug: Palivizumab	Phase 2/Phase 3

Detailed Description

This study is a pivotal Phase 2/3 randomized, double-blind, palivizumab-controlled study to evaluate the safety, pharmacokinetics (PK), anti-drug antibody (ADA) response, and descriptive efficacy for MEDI8897 in high-risk infants eligible to receive palivizumab when entering their first or second RSV season (Season 1 or Season 2, respectively). Approximately 900 palivizumab-eligible infants entering their first RSV season will be enrolled into one of 2 cohorts: (1) preterm cohort, including approximately 600 preterm infants (≤ 35 weeks gestational age [GA]) without CLD/CHD, or (2) CLD/CHD cohort, including approximately 300 infants with CLD of prematurity or hemodynamically significant CHD. A minimum of 100 infants with hemodynamically significant CHD will be enrolled. Within each cohort, randomization will be stratified by hemisphere (northern, southern) and subject age at the time of Season 1 randomization (≤ 3 months, > 3 to ≤ 6 months, > 6 months).

Study Design

Study Type:

Interventional

Actual Enrollment :

925 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

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

Primary Purpose:

Prevention

Official Title:

A Phase 2/3 Randomized, Double-blind, Palivizumab-controlled Study to Evaluate the Safety of MEDI8897, a Monoclonal Antibody With an Extended Half-life Against Respiratory Syncytial Virus, in High-risk Children (MEDLEY)

Actual Study Start Date :

Jul 30, 2019

Actual Primary Completion Date :

May 3, 2021

Anticipated Study Completion Date :

Nov 21, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: MEDI8897 anti-RSV monoclonal antibody with an extended half-life	Drug: MEDI8897 Anti-RSV monoclonal antibody with an extended half-life
Active Comparator: Palivizumab anti-RSV monoclonal antibody	Drug: Palivizumab Approved anti-RSV monoclonal antibody

Arm

Intervention/Treatment

Experimental: MEDI8897

anti-RSV monoclonal antibody with an extended half-life

Drug: MEDI8897

Anti-RSV monoclonal antibody with an extended half-life

Active Comparator: Palivizumab

anti-RSV monoclonal antibody

Drug: Palivizumab

Approved anti-RSV monoclonal antibody

Outcome Measures

Primary Outcome Measures

Safety and tolerability of MEDI8897 as assessed by the occurence of all treatment emergent adverse events (TEAESs) and treatment emergent serious adverse events (TESAE) [360 days post dose]
Safety and tolerability of MEDI8897 will be assessed by the occurrence of all treatment-emergent adverse events (TEAEs), treatment-emergent serious adverse events (TESAEs) , adverse events of special interest (AESIs), and new onset chronic diseases (NOCDs)

Secondary Outcome Measures

Evaluate serum concentrations of MEDI8897 and palivizumab [360 days post dose]
Individual MEDI8897 and palivizumab serum concentration data will be tabulated by treatment group along with descriptive statistics. PK parameters will be estimated using non compartmental analysis, if data permit.
Incidence of anti-drug antibody to MEDI8897 and palivizumab in serum [360 days post dose]
The incidence of ADA to MEDI8897 and palivizumab will be assessed and summarized by number and percentage of subjects that are ADA positive by treatment group.
Assess the descriptive efficacy of MEDI8897 in reducing medically attended LRTI incidence and hospitalization due to Reverse Transcriptase Chain Reaction (RT-PCR) confirmed RSV [150 days post dose]
Incidence of medically attended LRTI (inpatient and outpatient) due to RT-PCR-confirmed RSV through 150 days after Dose 1 for season 1 and season 2

Eligibility Criteria

Criteria

Ages Eligible for Study:

0 Years to 1 Year

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion criteria

For the preterm cohort (excluding subjects with CLD or hemodynamically significant CHD): preterm infants in their first year of life and born ≤ 35 weeks 0 days GA eligible to receive palivizumab in accordance with national or local guidelines, including those with:
Uncomplicated small atrial or ventricular septal defects or patent ductus arteriosus, or
Aortic stenosis, pulmonic stenosis, or coarctation of the aorta alone
For the CLD/CHD cohort:
Subjects with CLD - infants in their first year of life and a diagnosis of CLD of prematurity requiring medical intervention/management (ie, supplemental oxygen, bronchodilators, or diuretics) within the 6 months prior to randomization
Subjects with CHD - infants in their first year of life and documented, hemodynamically significant CHD (must be unoperated or partially corrected CHD) Note: Infants with hemodynamically significant acyanotic cardiac lesions must have pulmonary hypertension (≥ 40 mmHg measured pressure in the pulmonary artery) or the need for daily medication to manage CHD
Infants who are entering their first RSV season at the time of screening
Written informed consent and any locally required authorization (eg, Health Insurance Portability and Accountability Act in the USA, EU Data Privacy Directive in the EU) obtained from the subject's parent(s)/legal representative(s) prior to performing any protocol-related procedures, including screening evaluations
Subject's parent(s)/legal representative(s) able to understand and comply with the requirements of the protocol including follow-up and illness visits as judged by the investigator
Subject is available to complete the follow-up period, which will be 1 year after Season 1/ Dose 1 for subjects without CLD/CHD, or 1 year after Season 2/Dose 1 (or last replacement dose as applicable for CHD) for subjects with CLD/CHD

Exclusion criteria

Any fever (≥ 100.4°F [≥ 38.0°C], regardless of route) or acute illness within 7 days prior to randomization
Any history of LRTI or active LRTI prior to, or at the time of, randomization
Known history of RSV infection or active RSV infection prior to, or at the time of, randomization
Hospitalization at the time of randomization, unless discharge is expected within the 7 days after randomization
Requirement for mechanical ventilation, extracorporeal membrane oxygenation, CPAP, or other mechanical respiratory or cardiac support at the time of randomization
Anticipated cardiac surgery within 2 weeks after randomization
Anticipated survival of < 6 months after randomization
Receipt of any investigational drug
Known renal impairment
Known hepatic dysfunction including known or suspected active or chronic hepatitis infection
Clinically significant congenital anomaly of the respiratory tract
Chronic seizure, or evolving or unstable neurologic disorder
Prior history of a suspected or actual acute life-threatening event
Known immunodeficiency, including human immunodeficiency virus (HIV)
Mother with HIV infection (unless the child has been proven to be not infected)
Any known allergy, including to immunoglobulin products, or history of allergic reaction
Receipt of palivizumab or other RSV mAb or any RSV vaccine, including maternal RSV vaccination
Receipt of any monoclonal or polyclonal antibody (for example, hepatitis B immune globulin, intravenous immunoglobulin) or anticipated use during the study
Any condition that, in the opinion of the investigator, would interfere with evaluation of the study drug or interpretation of subject safety or study results
Concurrent enrollment in another interventional study
Children of employees of the sponsor, clinical study site, or any other individuals involved with the conduct of the study, or immediate family members of such individuals

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Anaheim	California	United States	92804
2	Research Site	Long Beach	California	United States	90806
3	Research Site	Los Angeles	California	United States	90027
4	Research Site	National City	California	United States	91950
5	Research Site	Paramount	California	United States	90723
6	Research Site	West Covina	California	United States	91790
7	Research Site	Aurora	Colorado	United States	80045
8	Research Site	Colorado Springs	Colorado	United States	80922
9	Research Site	Washington	District of Columbia	United States	20016
10	Research Site	Atlanta	Georgia	United States	30322
11	Research Site	Chicago	Illinois	United States	60611
12	Research Site	Indianapolis	Indiana	United States	46202
13	Research Site	South Bend	Indiana	United States	46617
14	Research Site	West Des Moines	Iowa	United States	50266
15	Research Site	Louisville	Kentucky	United States	40202
16	Research Site	Jackson	Mississippi	United States	39216
17	Research Site	Columbia	Missouri	United States	65201
18	Research Site	Mineola	New York	United States	11501
19	Research Site	Syracuse	New York	United States	13210
20	Research Site	Durham	North Carolina	United States	27710
21	Research Site	Greenville	North Carolina	United States	27834
22	Research Site	Cincinnati	Ohio	United States	45229
23	Research Site	Columbus	Ohio	United States	43205
24	Research Site	Greenville	South Carolina	United States	29607
25	Research Site	Corpus Christi	Texas	United States	78411
26	Research Site	Layton	Utah	United States	84041
27	Research Site	Saint George	Utah	United States	84790
28	Research Site	Charlottesville	Virginia	United States	22902
29	Research Site	Seattle	Washington	United States	98105
30	Research Site	Morgantown	West Virginia	United States	26506
31	Research Site	Graz		Austria	8036
32	Research Site	Bruxelles		Belgium	1200
33	Research Site	Gent		Belgium	9000
34	Research Site	Montana		Bulgaria	3400
35	Research Site	Pazardzhik		Bulgaria	4400
36	Research Site	Pleven		Bulgaria	5800
37	Research Site	Plovdiv		Bulgaria	4000
38	Research Site	Plovdiv		Bulgaria	4003
39	Research Site	Ruse		Bulgaria	7002
40	Research Site	Sliven		Bulgaria	8800
41	Research Site	Sofia		Bulgaria	1309
42	Research Site	Sofia		Bulgaria	1407
43	Research Site	Veliko Tarnovo		Bulgaria	5000
44	Research Site	Edmonton	Alberta	Canada	T6G 1C9
45	Research Site	Vancouver	British Columbia	Canada	V6H 3V4
46	Research Site	Praha 4		Czechia	14710
47	Research Site	Tallinn		Estonia	13419
48	Research Site	Tartu		Estonia	51014
49	Research Site	Tampere		Finland	33100
50	Research Site	Amiens Cedex 1		France	80054
51	Research Site	Bordeaux		France	33000
52	Research Site	Brest		France	29609
53	Research Site	Bron		France	69677
54	Research Site	Caen		France	1403
55	Research Site	Creteil Cedex		France	94010
56	Research Site	Grenoble Cedex 9		France	38043
57	Research Site	Marseille		France	13015
58	Research Site	Pau Cedex		France	64046
59	Research Site	Frankenthal		Germany	67227
60	Research Site	Leipzig		Germany	04103
61	Research Site	Mannheim		Germany	68161
62	Research Site	Baja		Hungary	6500
63	Research Site	Budapest		Hungary	1096
64	Research Site	Debrecen		Hungary	4032
65	Research Site	Kecskemét		Hungary	6000
66	Research Site	Miskolc		Hungary	3526
67	Research Site	Pisa		Italy	56126
68	Research Site	Verona		Italy	37126
69	Research Site	Fukui-shi		Japan	918-8503
70	Research Site	Fukuoka-shi		Japan	813-0017
71	Research Site	Kitakyusyu-shi		Japan	806-8501
72	Research Site	Maebashi-shi		Japan	371-0811
73	Research Site	Saitama shi		Japan	336 8522
74	Research Site	Setagaya-ku		Japan	157-8535
75	Research Site	Ansan-si		Korea, Republic of	15355
76	Research Site	Seoul		Korea, Republic of	06351
77	Research Site	Suwon-si		Korea, Republic of	16499
78	Research Site	Jekabpils		Latvia	LV-5201
79	Research Site	Riga		Latvia	1004
80	Research Site	Riga		Latvia	LV1002
81	Research Site	Kaunas		Lithuania	48259
82	Research Site	Kaunas		Lithuania	50161
83	Research Site	Cuernavaca		Mexico	62290
84	Research Site	Mexico		Mexico	06720
85	Research Site	Christchurch		New Zealand	8011
86	Research Site	Bydgoszcz		Poland	85 168
87	Research Site	Gdańsk		Poland	80-214
88	Research Site	Krakow		Poland	31-624
89	Research Site	Kraków		Poland	30-348
90	Research Site	Wrocław		Poland	51-169
91	Research Site	Kazan		Russian Federation	420012
92	Research Site	Novosibirsk		Russian Federation	630089
93	Research Site	Perm		Russian Federation	614066
94	Research Site	Saint Petersburg		Russian Federation	191025
95	Research Site	Saint Petersburg		Russian Federation	197341
96	Research Site	St Petersburg		Russian Federation	193312
97	Research Site	Yaroslavl		Russian Federation	150003
98	Research Site	Cape Town		South Africa	7505
99	Research Site	Cape Town		South Africa	7800
100	Research Site	Johannesburg		South Africa	2112
101	Research Site	Johannesburg		South Africa	2193
102	Research Site	Pretoria		South Africa	0087
103	Research Site	Pretoria		South Africa	0101
104	Research Site	Soweto		South Africa	2013
105	Research Site	Alicante		Spain	03010
106	Research Site	Boadilla del Monte		Spain	28660
107	Research Site	Elche		Spain	03203
108	Research Site	Leganes		Spain	28911
109	Research Site	Lleida		Spain	25198
110	Research Site	Madrid		Spain	28046
111	Research Site	Malaga		Spain	29004
112	Research Site	Pozuelo de Alarcon		Spain	28223
113	Research Site	Sant Cugat del Valles		Spain	08190
114	Research Site	Tarragona		Spain	43007
115	Research Site	Stockholm		Sweden	118 83
116	Research Site	Adana		Turkey	01330
117	Research Site	Izmir		Turkey	35100
118	Research Site	Kocaeli		Turkey	41380
119	Research Site	Chernivtsі		Ukraine	58001
120	Research Site	Dnipro		Ukraine	49006
121	Research Site	Ivano-Frankivsk		Ukraine	76014
122	Research Site	Kharkiv Region		Ukraine	61093
123	Research Site	Odesa		Ukraine	65031
124	Research Site	Sumy		Ukraine	40022
125	Research Site	Vinnytsia		Ukraine	21000
126	Research Site	Leicester		United Kingdom	LE3 9QP
127	Research Site	London		United Kingdom	W2 1NY
128	Research Site	Nottingham		United Kingdom	NG7 2UH