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

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ClinicalTrials.gov Identifier: NCT03959488

Recruitment Status : Completed

First Posted : May 22, 2019

Results First Posted : September 21, 2023

Last Update Posted : September 21, 2023

View this study on the modernized ClinicalTrials.gov

Sponsor:

Information provided by (Responsible Party):

AstraZeneca

Tracking Information

First Submitted Date ^ICMJE

May 21, 2019

First Posted Date ^ICMJE

May 22, 2019

Results First Submitted Date ^ICMJE

August 16, 2023

Results First Posted Date ^ICMJE

September 21, 2023

Last Update Posted Date

September 21, 2023

Actual Study Start Date ^ICMJE

July 30, 2019

Actual Primary Completion Date

May 3, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures ^ICMJE

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) [ Time Frame: 360 days post first 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 ^ICMJE

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 ]

Change History

Current Secondary Outcome Measures ^ICMJE

Serum Concentrations of MEDI8897 and Palivizumab [ Time Frame: Day 15, Day 31, Day 151 post first dose in Season 1 and Season 2 ]
Summary of individual MEDI8897 and palivizumab serum concentration data by treatment group along with descriptive statistics.
Incidence of Anti-drug Antibody (ADA) to MEDI8897 and Palivizumab in Serum [ Time Frame: 360 days post first dose ]
Incidence of ADA to MEDI8897 and palivizumab as assessed by the percentage of participants with any post-baseline ADA positive by treatment group.
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 [ Time Frame: 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.

Original Secondary Outcome Measures ^ICMJE

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

Current Other Pre-specified Outcome Measures

Not Provided

Original Other Pre-specified Outcome Measures

Not Provided

Descriptive Information

Brief Title ^ICMJE

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 ^ICMJE

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 ^ICMJE

Interventional

Study Phase ^ICMJE

Phase 2
Phase 3

Study Design ^ICMJE

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention

Condition ^ICMJE

Respiratory Syncytial Virus Infections

Intervention ^ICMJE

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

Study Arms ^ICMJE

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.

* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.

Recruitment Information

Recruitment Status ^ICMJE

Completed

Actual Enrollment ^ICMJE

925

Original Estimated Enrollment ^ICMJE

1500

Actual Study Completion Date ^ICMJE

January 20, 2023

Actual Primary Completion Date

May 3, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria ^ICMJE

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

Sex/Gender ^ICMJE

Sexes Eligible for Study:

All

Ages ^ICMJE

0 Years to 1 Year (Child)

Accepts Healthy Volunteers ^ICMJE

Contacts ^ICMJE

Contact information is only displayed when the study is recruiting subjects

Listed Location Countries ^ICMJE

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 ^ICMJE

NCT03959488

Other Study ID Numbers ^ICMJE

D5290C00005
2019-000201-69 ( EudraCT Number )

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 ^ICMJE

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