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

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)

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.

Study Overview

• Status: Completed
• Conditions: Respiratory Syncytial Virus Infections
• Intervention / Treatment: Drug: MEDI8897; Drug: Palivizumab

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 Type: Interventional
• Enrollment (Actual): 925
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Austria
  • Graz, Austria, 8036
    • Research Site
• Belgium
  • Bruxelles, Belgium, 1200
    • Research Site
  • Gent, Belgium, 9000
    • Research Site
• Bulgaria
  • Montana, Bulgaria, 3400
    • Research Site
  • Pazardzhik, Bulgaria, 4400
    • Research Site
  • Pleven, Bulgaria, 5800
    • Research Site
  • Plovdiv, Bulgaria, 4003
    • Research Site
  • Plovdiv, Bulgaria, 4000
    • Research Site
  • Ruse, Bulgaria, 7002
    • Research Site
  • Sliven, Bulgaria, 8800
    • Research Site
  • Sofia, Bulgaria, 1407
    • Research Site
  • Sofia, Bulgaria, 1309
    • Research Site
  • Veliko Tarnovo, Bulgaria, 5000
    • Research Site
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1C9
      • Research Site
  • British Columbia
    • Vancouver, British Columbia, Canada, V6H 3V4
      • Research Site
• Czechia
  • Praha 4, Czechia, 14710
    • Research Site
• Estonia
  • Tallinn, Estonia, 13419
    • Research Site
  • Tartu, Estonia, 51014
    • Research Site
• Finland
  • Tampere, Finland, 33100
    • Research Site
• France
  • Amiens Cedex 1, France, 80054
    • Research Site
  • Bordeaux, France, 33000
    • Research Site
  • Brest, France, 29609
    • Research Site
  • Bron, France, 69677
    • Research Site
  • Caen, France, 1403
    • Research Site
  • Creteil Cedex, France, 94010
    • Research Site
  • Grenoble Cedex 9, France, 38043
    • Research Site
  • Marseille, France, 13015
    • Research Site
  • Pau Cedex, France, 64046
    • Research Site
• Germany
  • Frankenthal, Germany, 67227
    • Research Site
  • Leipzig, Germany, 04103
    • Research Site
  • Mannheim, Germany, 68161
    • Research Site
• Hungary
  • Baja, Hungary, 6500
    • Research Site
  • Budapest, Hungary, 1096
    • Research Site
  • Debrecen, Hungary, 4032
    • Research Site
  • Kecskemét, Hungary, 6000
    • Research Site
  • Miskolc, Hungary, 3526
    • Research Site
• Italy
  • Pisa, Italy, 56126
    • Research Site
  • Verona, Italy, 37126
    • Research Site
• Japan
  • Fukui-shi, Japan, 918-8503
    • Research Site
  • Fukuoka-shi, Japan, 813-0017
    • Research Site
  • Kitakyusyu-shi, Japan, 806-8501
    • Research Site
  • Maebashi-shi, Japan, 371-0811
    • Research Site
  • Saitama shi, Japan, 336 8522
    • Research Site
  • Setagaya-ku, Japan, 157-8535
    • Research Site
• Korea, Republic of
  • Ansan-si, Korea, Republic of, 15355
    • Research Site
  • Seoul, Korea, Republic of, 06351
    • Research Site
  • Suwon-si, Korea, Republic of, 16499
    • Research Site
• Latvia
  • Jekabpils, Latvia, LV-5201
    • Research Site
  • Riga, Latvia, 1004
    • Research Site
  • Riga, Latvia, LV1002
    • Research Site
• Lithuania
  • Kaunas, Lithuania, 48259
    • Research Site
  • Kaunas, Lithuania, 50161
    • Research Site
• Mexico
  • Cuernavaca, Mexico, 62290
    • Research Site
  • Mexico, Mexico, 06720
    • Research Site
• New Zealand
  • Christchurch, New Zealand, 8011
    • Research Site
• Poland
  • Bydgoszcz, Poland, 85 168
    • Research Site
  • Gdańsk, Poland, 80-214
    • Research Site
  • Krakow, Poland, 31-624
    • Research Site
  • Kraków, Poland, 30-348
    • Research Site
  • Wrocław, Poland, 51-169
    • Research Site
• Russian Federation
  • Kazan, Russian Federation, 420012
    • Research Site
  • Novosibirsk, Russian Federation, 630089
    • Research Site
  • Perm, Russian Federation, 614066
    • Research Site
  • Saint Petersburg, Russian Federation, 197341
    • Research Site
  • Saint Petersburg, Russian Federation, 191025
    • Research Site
  • St Petersburg, Russian Federation, 193312
    • Research Site
  • Yaroslavl, Russian Federation, 150003
    • Research Site
• South Africa
  • Cape Town, South Africa, 7505
    • Research Site
  • Cape Town, South Africa, 7800
    • Research Site
  • Johannesburg, South Africa, 2193
    • Research Site
  • Johannesburg, South Africa, 2112
    • Research Site
  • Pretoria, South Africa, 0101
    • Research Site
  • Pretoria, South Africa, 0087
    • Research Site
  • Soweto, South Africa, 2013
    • Research Site
• Spain
  • Alicante, Spain, 03010
    • Research Site
  • Boadilla del Monte, Spain, 28660
    • Research Site
  • Elche, Spain, 03203
    • Research Site
  • Leganes, Spain, 28911
    • Research Site
  • Lleida, Spain, 25198
    • Research Site
  • Madrid, Spain, 28046
    • Research Site
  • Malaga, Spain, 29004
    • Research Site
  • Pozuelo de Alarcon, Spain, 28223
    • Research Site
  • Sant Cugat del Valles, Spain, 08190
    • Research Site
  • Tarragona, Spain, 43007
    • Research Site
• Sweden
  • Stockholm, Sweden, 118 83
    • Research Site
• Turkey
  • Adana, Turkey, 01330
    • Research Site
  • Izmir, Turkey, 35100
    • Research Site
  • Kocaeli, Turkey, 41380
    • Research Site
• Ukraine
  • Chernivtsі, Ukraine, 58001
    • Research Site
  • Dnipro, Ukraine, 49006
    • Research Site
  • Ivano-Frankivsk, Ukraine, 76014
    • Research Site
  • Kharkiv Region, Ukraine, 61093
    • Research Site
  • Odesa, Ukraine, 65031
    • Research Site
  • Sumy, Ukraine, 40022
    • Research Site
  • Vinnytsia, Ukraine, 21000
    • Research Site
• United Kingdom
  • Leicester, United Kingdom, LE3 9QP
    • Research Site
  • London, United Kingdom, W2 1NY
    • Research Site
  • Nottingham, United Kingdom, NG7 2UH
    • Research Site
• United States
  • California
    • Anaheim, California, United States, 92804
      • Research Site
    • Long Beach, California, United States, 90806
      • Research Site
    • Los Angeles, California, United States, 90027
      • Research Site
    • National City, California, United States, 91950
      • Research Site
    • Paramount, California, United States, 90723
      • Research Site
    • West Covina, California, United States, 91790
      • Research Site
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Research Site
    • Colorado Springs, Colorado, United States, 80922
      • Research Site
  • District of Columbia
    • Washington, District of Columbia, United States, 20016
      • Research Site
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Research Site
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Research Site
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Research Site
    • South Bend, Indiana, United States, 46617
      • Research Site
  • Iowa
    • West Des Moines, Iowa, United States, 50266
      • Research Site
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Research Site
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • Research Site
  • Missouri
    • Columbia, Missouri, United States, 65201
      • Research Site
  • New York
    • Mineola, New York, United States, 11501
      • Research Site
    • Syracuse, New York, United States, 13210
      • Research Site
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Research Site
    • Greenville, North Carolina, United States, 27834
      • Research Site
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Research Site
    • Columbus, Ohio, United States, 43205
      • Research Site
  • South Carolina
    • Greenville, South Carolina, United States, 29607
      • Research Site
  • Texas
    • Corpus Christi, Texas, United States, 78411
      • Research Site
  • Utah
    • Layton, Utah, United States, 84041
      • Research Site
    • Saint George, Utah, United States, 84790
      • Research Site
  • Virginia
    • Charlottesville, Virginia, United States, 22902
      • Research Site
  • Washington
    • Seattle, Washington, United States, 98105
      • Research Site
  • West Virginia
    • Morgantown, West Virginia, United States, 26506
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 second to 1 year (Child)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	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)	360 days post first dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum Concentrations of MEDI8897 and Palivizumab	Summary of individual MEDI8897 and palivizumab serum concentration data by treatment group along with descriptive statistics.	Day 15, Day 31, Day 151 post first dose in Season 1 and Season 2
Incidence of Anti-drug Antibody (ADA) to MEDI8897 and Palivizumab in Serum	Incidence of ADA to MEDI8897 and palivizumab as assessed by the percentage of participants with any post-baseline ADA positive by treatment group.	360 days post first dose
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	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. Incidence of LRTI hospitalizations due to RT-PCR-confirmed RSV through 150 days after Dose 1 for season 1 and season 2.	150 days post first dose

Collaborators and Investigators

• Sponsor: AstraZeneca

Publications and helpful links

General Publications

• 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.

Helpful Links

• CSR Synopsis
• MEDLEY Protocol
• Statistical Analysis Plan (SAP)

Study record dates

Study Major Dates

• Study Start (Actual): July 30, 2019
• Primary Completion (Actual): May 3, 2021
• Study Completion (Actual): January 20, 2023

Study Registration Dates

• First Submitted: May 21, 2019
• First Submitted That Met QC Criteria: May 21, 2019
• First Posted (Actual): May 22, 2019

Study Record Updates

• Last Update Posted (Actual): September 21, 2023
• Last Update Submitted That Met QC Criteria: September 20, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Preterm Infants; Respiratory Syncytial Virus Infections; Lower Respiratory Infection
• Additional Relevant MeSH Terms: Pathologic Processes; RNA Virus Infections; Disease Attributes; Paramyxoviridae Infections; Mononegavirales Infections; Pneumovirus Infections; Infections; Communicable Diseases; Virus Diseases; Respiratory Syncytial Virus Infections; Anti-Infective Agents; Antiviral Agents; Palivizumab
• Other Study ID Numbers: D5290C00005; 2019-000201-69 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No