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

• ClinicalTrials.gov Identifier: NCT03959488
• Recruitment Status: Active, not recruiting
• First Posted: May 22, 2019
• Last Update Posted: August 22, 2022
• Sponsor: AstraZeneca
• Information provided by (Responsible Party): AstraZeneca

Tracking Information

• First Submitted Date: May 21, 2019
• First Posted Date: May 22, 2019
• Last Update Posted Date: August 22, 2022
• Actual Study Start Date: July 30, 2019
• Actual Primary Completion Date: May 3, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 21, 2019)

Safety and tolerability of MEDI8897 as assessed by the occurence of all treatment emergent adverse events (TEAESs) and treatment emergent serious adverse events (TESAE) [ Time Frame: 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)

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: May 21, 2019)

• Evaluate serum concentrations of MEDI8897 and palivizumab [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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)
• 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).
• Study Type: Interventional
• Study Phase: Phase 2; Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Prevention
• Condition: Respiratory Syncytial Virus Infections

Intervention

• Drug: MEDI8897
  Anti-RSV monoclonal antibody with an extended half-life
• Drug: Palivizumab
  Approved anti-RSV monoclonal antibody

Study Arms

• Experimental: MEDI8897
  anti-RSV monoclonal antibody with an extended half-life
  Intervention: Drug: MEDI8897
• Active Comparator: Palivizumab
  anti-RSV monoclonal antibody
  Intervention: Drug: Palivizumab

• 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.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: August 18, 2022): 925
• Original Estimated Enrollment (submitted: May 21, 2019): 1500
• Estimated Study Completion Date: November 21, 2022
• Actual Primary Completion Date: May 3, 2021 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 0 Years to 1 Year (Child)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Austria, Belgium, Bulgaria, Canada, Czechia, Estonia, Finland, France, Germany, Hungary, Italy, Japan, Korea, Republic of, Latvia, Lithuania, Mexico, New Zealand, Poland, Russian Federation, South Africa, Spain, Sweden, Turkey, Ukraine, United Kingdom, United States
• Removed Location Countries: Argentina, Australia, Brazil, Chile, Colombia, Israel, Panama

Administrative Information

• NCT Number: NCT03959488
• Other Study ID Numbers: D5290C00005
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• 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.
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• 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.
• 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.
• URL: https://astrazenecagroup-dt.pharmacm.com/DT/Home

• Current Responsible Party: AstraZeneca
• Original Responsible Party: MedImmune LLC
• Current Study Sponsor: AstraZeneca
• Original Study Sponsor: MedImmune LLC
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: AstraZeneca
• Verification Date: August 2022