Clinical trial NCT03959488: 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
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Respiratory Syncytial Virus Infections
Keywords: Respiratory Syncytial Virus Infections
Preterm Infants
Lower Respiratory Infection
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2019-05-22
Enrollment: 925
Sex: ALL
Minimum age (years): 0
Maximum age (years): 1
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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).

Eligibility criteria: Inclusion criteria

1. 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:

   1. Uncomplicated small atrial or ventricular septal defects or patent ductus arteriosus, or
   2. Aortic stenosis, pulmonic stenosis, or coarctation of the aorta alone
2. For the CLD/CHD cohort:

   1. 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
   2. 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
3. Infants who are entering their first RSV season at the time of screening
4. 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
5. 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
6. 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

1. Any fever (≥ 100.4°F \[≥ 38.0°C\], regardless of route) or acute illness within 7 days prior to randomization
2. Any history of LRTI or active LRTI prior to, or at the time of, randomization
3. Known history of RSV infection or active RSV infection prior to, or at the time of, randomization
4. Hospitalization at the time of randomization, unless discharge is expected within the 7 days after randomization
5. Requirement for mechanical ventilation, extracorporeal membrane oxygenation, CPAP, or other mechanical respiratory or cardiac support at the time of randomization
6. Anticipated cardiac surgery within 2 weeks after randomization
7. Anticipated survival of \< 6 months after randomization
8. Receipt of any investigational drug
9. Known renal impairment
10. Known hepatic dysfunction including known or suspected active or chronic hepatitis infection
11. Clinically significant congenital anomaly of the respiratory tract
12. Chronic seizure, or evolving or unstable neurologic disorder
13. Prior history of a suspected or actual acute life-threatening event
14. Known immunodeficiency, including human immunodeficiency virus (HIV)
15. Mother with HIV infection (unless the child has been proven to be not infected)
16. Any known allergy, including to immunoglobulin products, or history of allergic reaction
17. Receipt of palivizumab or other RSV mAb or any RSV vaccine, including maternal RSV vaccination
18. Receipt of any monoclonal or polyclonal antibody (for example, hepatitis B immune globulin, intravenous immunoglobulin) or anticipated use during the study
19. 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
20. Concurrent enrollment in another interventional study
21. 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

Primary outcomes:
measure: Safety and Tolerability of MEDI8897 as Assessed by the Occurrence of All Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) and Adverse Events of Special Interest (AESIs) and New Onset Chronic Disease (NOCD)
timeFrame: 360 days post first dose
Secondary outcomes:
measure: Serum Concentrations of MEDI8897 and Palivizumab
timeFrame: Day 15, Day 31, Day 151 post first dose in Season 1 and Season 2
measure: Incidence of Anti-drug Antibody (ADA) to MEDI8897 and Palivizumab in Serum
timeFrame: 360 days post first dose
measure: Incidence of Medically Attended Lower Respiratory Track Infection (LRTI) and Hospitalization Due to Reverse Transcriptase Chain Reaction (RT-PCR) Confirmed Respiratory Syncytial Virus (RSV) Through 150 Days Post First Dose
timeFrame: 150 days post first dose
Other outcomes:
Locations:
city: Anaheim
country: United States
facility: Research Site
state: California
city: Long Beach
country: United States
facility: Research Site
state: California
city: Los Angeles
country: United States
facility: Research Site
state: California
city: National City
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facility: Research Site
state: California
city: Paramount
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facility: Research Site
state: California
city: West Covina
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facility: Research Site
state: California
city: Aurora
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facility: Research Site
state: Colorado
city: Colorado Springs
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state: Colorado
city: Washington
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state: District of Columbia
city: Atlanta
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state: Georgia
city: Chicago
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state: Illinois
city: Indianapolis
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state: Indiana
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city: West Des Moines
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state: Mississippi
city: Columbia
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state: Missouri
city: Mineola
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state: New York
city: Syracuse
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state: New York
city: Durham
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state: North Carolina
city: Greenville
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state: North Carolina
city: Cincinnati
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state: Ohio
city: Columbus
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state: Ohio
city: Greenville
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state: South Carolina
city: Corpus Christi
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state: Texas
city: Layton
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state: Utah
city: Saint George
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state: Utah
city: Charlottesville
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state: Virginia
city: Seattle
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state: Washington
city: Morgantown
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state: West Virginia
city: Graz
country: Austria
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city: Bruxelles
country: Belgium
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city: Gent
country: Belgium
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city: Montana
country: Bulgaria
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city: Pazardzhik
country: Bulgaria
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city: Pleven
country: Bulgaria
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city: Plovdiv
country: Bulgaria
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city: Plovdiv
country: Bulgaria
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city: Ruse
country: Bulgaria
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city: Sliven
country: Bulgaria
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city: Sofia
country: Bulgaria
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city: Sofia
country: Bulgaria
facility: Research Site
city: Veliko Tarnovo
country: Bulgaria
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city: Edmonton
country: Canada
facility: Research Site
state: Alberta
city: Vancouver
country: Canada
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state: British Columbia
city: Praha 4
country: Czechia
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city: Tallinn
country: Estonia
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city: Tartu
country: Estonia
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city: Tampere
country: Finland
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city: Amiens Cedex 1
country: France
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city: Bordeaux
country: France
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city: Brest
country: France
facility: Research Site
city: Bron
country: France
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city: Caen
country: France
facility: Research Site
city: Creteil Cedex
country: France
facility: Research Site
city: Grenoble Cedex 9
country: France
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city: Marseille
country: France
facility: Research Site
city: Pau Cedex
country: France
facility: Research Site
city: Frankenthal
country: Germany
facility: Research Site
city: Leipzig
country: Germany
facility: Research Site
city: Mannheim
country: Germany
facility: Research Site
city: Baja
country: Hungary
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city: Budapest
country: Hungary
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city: Debrecen
country: Hungary
facility: Research Site
city: Kecskemét
country: Hungary
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city: Miskolc
country: Hungary
facility: Research Site
city: Pisa
country: Italy
facility: Research Site
city: Verona
country: Italy
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city: Fukui-shi
country: Japan
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city: Fukuoka-shi
country: Japan
facility: Research Site
city: Kitakyusyu-shi
country: Japan
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city: Maebashi-shi
country: Japan
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city: Saitama shi
country: Japan
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city: Setagaya-ku
country: Japan
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city: Ansan-si
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Suwon-si
country: Korea, Republic of
facility: Research Site
city: Jekabpils
country: Latvia
facility: Research Site
city: Riga
country: Latvia
facility: Research Site
city: Riga
country: Latvia
facility: Research Site
city: Kaunas
country: Lithuania
facility: Research Site
city: Kaunas
country: Lithuania
facility: Research Site
city: Cuernavaca
country: Mexico
facility: Research Site
city: Mexico
country: Mexico
facility: Research Site
city: Christchurch
country: New Zealand
facility: Research Site
city: Bydgoszcz
country: Poland
facility: Research Site
city: Gdańsk
country: Poland
facility: Research Site
city: Krakow
country: Poland
facility: Research Site
city: Kraków
country: Poland
facility: Research Site
city: Wrocław
country: Poland
facility: Research Site
city: Kazan
country: Russian Federation
facility: Research Site
city: Novosibirsk
country: Russian Federation
facility: Research Site
city: Perm
country: Russian Federation
facility: Research Site
city: Saint Petersburg
country: Russian Federation
facility: Research Site
city: Saint Petersburg
country: Russian Federation
facility: Research Site
city: St Petersburg
country: Russian Federation
facility: Research Site
city: Yaroslavl
country: Russian Federation
facility: Research Site
city: Cape Town
country: South Africa
facility: Research Site
city: Cape Town
country: South Africa
facility: Research Site
city: Johannesburg
country: South Africa
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city: Johannesburg
country: South Africa
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city: Pretoria
country: South Africa
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city: Pretoria
country: South Africa
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city: Soweto
country: South Africa
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city: Alicante
country: Spain
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city: Boadilla del Monte
country: Spain
facility: Research Site
city: Elche
country: Spain
facility: Research Site
city: Leganes
country: Spain
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city: Lleida
country: Spain
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city: Madrid
country: Spain
facility: Research Site
city: Malaga
country: Spain
facility: Research Site
city: Pozuelo de Alarcon
country: Spain
facility: Research Site
city: Sant Cugat del Valles
country: Spain
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city: Tarragona
country: Spain
facility: Research Site
city: Stockholm
country: Sweden
facility: Research Site
city: Adana
country: Turkey
facility: Research Site
city: Izmir
country: Turkey
facility: Research Site
city: Kocaeli
country: Turkey
facility: Research Site
city: Chernivtsі
country: Ukraine
facility: Research Site
city: Dnipro
country: Ukraine
facility: Research Site
city: Ivano-Frankivsk
country: Ukraine
facility: Research Site
city: Kharkiv Region
country: Ukraine
facility: Research Site
city: Odesa
country: Ukraine
facility: Research Site
city: Sumy
country: Ukraine
facility: Research Site
city: Vinnytsia
country: Ukraine
facility: Research Site
city: Leicester
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: Nottingham
country: United Kingdom
facility: Research Site
Study officials:
References:
citation: Domachowske J, Madhi SA, Simoes EAF, Atanasova V, Cabanas F, Furuno K, Garcia-Garcia ML, Grantina I, Nguyen KA, Brooks D, Chang Y, Leach A, Takas T, Yuan Y, Griffin MP, Mankad VS, Villafana T; MEDLEY Study Group. Safety of Nirsevimab for RSV in Infants with Heart or Lung Disease or Prematurity. N Engl J Med. 2022 Mar 3;386(9):892-894. doi: 10.1056/NEJMc2112186. No abstract available.