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

NCT ID: NCT03959488

Last Updated: 2023-09-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 925 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-07-30
• Study Completion Date: 2023-01-20

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).

Conditions

Respiratory Syncytial Virus Infections

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

MEDI8897

anti-RSV monoclonal antibody with an extended half-life

Group Type: EXPERIMENTAL

MEDI8897

Intervention Type: DRUG

Anti-RSV monoclonal antibody with an extended half-life

Palivizumab

anti-RSV monoclonal antibody

Group Type: ACTIVE_COMPARATOR

Palivizumab

Intervention Type: DRUG

Approved anti-RSV monoclonal antibody

Interventions

MEDI8897

Anti-RSV monoclonal antibody with an extended half-life

Intervention Type: DRUG

Palivizumab

Approved anti-RSV monoclonal antibody

Intervention Type: DRUG

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

• Minimum Eligible Age: 0 Years
• Maximum Eligible Age: 1 Year
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AstraZeneca

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Research Site

Anaheim, California, United States

Research Site

Long Beach, California, United States

Research Site

Los Angeles, California, United States

Research Site

National City, California, United States

Research Site

Paramount, California, United States

Research Site

West Covina, California, United States

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Aurora, Colorado, United States

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Colorado Springs, Colorado, United States

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Washington D.C., District of Columbia, United States

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Atlanta, Georgia, United States

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Chicago, Illinois, United States

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Indianapolis, Indiana, United States

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South Bend, Indiana, United States

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West Des Moines, Iowa, United States

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Louisville, Kentucky, United States

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Jackson, Mississippi, United States

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Columbia, Missouri, United States

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Mineola, New York, United States

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Syracuse, New York, United States

Research Site

Durham, North Carolina, United States

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Greenville, North Carolina, United States

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Cincinnati, Ohio, United States

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Columbus, Ohio, United States

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Greenville, South Carolina, United States

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Corpus Christi, Texas, United States

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Layton, Utah, United States

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St. George, Utah, United States

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Charlottesville, Virginia, United States

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Seattle, Washington, United States

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Morgantown, West Virginia, United States

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Graz, , Austria

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Brussels, , Belgium

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Ghent, , Belgium

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Montana, , Bulgaria

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Pazardzhik, , Bulgaria

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Pleven, , Bulgaria

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Plovdiv, , Bulgaria

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Plovdiv, , Bulgaria

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Rousse, , Bulgaria

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Sliven, , Bulgaria

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Sofia, , Bulgaria

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Sofia, , Bulgaria

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Veliko Tarnovo, , Bulgaria

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Edmonton, Alberta, Canada

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Vancouver, British Columbia, Canada

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Prague, , Czechia

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Tallinn, , Estonia

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Tartu, , Estonia

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Tampere, , Finland

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Amiens, , France

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Bordeaux, , France

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Brest, , France

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Bron, , France

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Caen, , France

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Créteil, , France

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Grenoble, , France

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Marseille, , France

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Pau, , France

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Frankenthal, , Germany

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Leipzig, , Germany

Research Site

Mannheim, , Germany

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Baja, , Hungary

Research Site

Budapest, , Hungary

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Debrecen, , Hungary

Research Site

Kecskemét, , Hungary

Research Site

Miskolc, , Hungary

Research Site

Pisa, , Italy

Research Site

Verona, , Italy

Research Site

Fukui-shi, , Japan

Research Site

Fukuoka, , Japan

Research Site

Kitakyusyu-shi, , Japan

Research Site

Maebashi, , Japan

Research Site

Saitama Shi, , Japan

Research Site

Setagaya-ku, , Japan

Research Site

Jēkabpils, , Latvia

Research Site

Riga, , Latvia

Research Site

Riga, , Latvia

Research Site

Kaunas, , Lithuania

Research Site

Kaunas, , Lithuania

Research Site

Cuernavaca, , Mexico

Research Site

México, , Mexico

Research Site

Christchurch, , New Zealand

Research Site

Bydgoszcz, , Poland

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Gdansk, , Poland

Research Site

Krakow, , Poland

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Krakow, , Poland

Research Site

Wroclaw, , Poland

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Kazan', , Russia

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Novosibirsk, , Russia

Research Site

Perm, , Russia

Research Site

Saint Petersburg, , Russia

Research Site

Saint Petersburg, , Russia

Research Site

Saint Petersburg, , Russia

Research Site

Yaroslavl, , Russia

Research Site

Cape Town, , South Africa

Research Site

Cape Town, , South Africa

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Johannesburg, , South Africa

Research Site

Johannesburg, , South Africa

Research Site

Pretoria, , South Africa

Research Site

Pretoria, , South Africa

Research Site

Soweto, , South Africa

Research Site

Ansan-si, , South Korea

Research Site

Seoul, , South Korea

Research Site

Suwon, , South Korea

Research Site

Alicante, , Spain

Research Site

Boadilla del Monte, , Spain

Research Site

Elche, , Spain

Research Site

Leganés, , Spain

Research Site

Lleida, , Spain

Research Site

Madrid, , Spain

Research Site

Málaga, , Spain

Research Site

Pozuelo de Alarcón, , Spain

Research Site

Sant Cugat del Vallès, , Spain

Research Site

Tarragona, , Spain

Research Site

Stockholm, , Sweden

Research Site

Adana, , Turkey (Türkiye)

Research Site

Izmir, , Turkey (Türkiye)

Research Site

Kocaeli, , Turkey (Türkiye)

Research Site

Chernivtsі, , Ukraine

Research Site

Dnipro, , Ukraine

Research Site

Ivano-Frankivsk, , Ukraine

Research Site

Kharkiv Region, , Ukraine

Research Site

Odesa, , Ukraine

Research Site

Sumy, , Ukraine

Research Site

Vinnytsia, , Ukraine

Research Site

Leicester, , United Kingdom

Research Site

London, , United Kingdom

Research Site

Nottingham, , United Kingdom

Countries

United States; Austria; Belgium; Bulgaria; Canada; Czechia; Estonia; Finland; France; Germany; Hungary; Italy; Japan; Latvia; Lithuania; Mexico; New Zealand; Poland; Russia; South Africa; South Korea; Spain; Sweden; Turkey (Türkiye); Ukraine; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 35235733 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://filehosting-v2.pharmacm.com/api/Attachment/Download?tenantId=80217111&amp;parentIdentifier=D5290C00005&amp;attachmentIdentifier=7817621f-6d8e-41e6-a839-c1ccdfed21c7&amp;fileName=d5290c00005-study-synopsis.pdf&amp;versionIdentifier=

CSR Synopsis

https://filehosting-v2.pharmacm.com/api/Attachment/Download?tenantId=80217111&amp;parentIdentifier=D5290C00005&amp;attachmentIdentifier=ba02bb70-712d-4844-908a-a17816e1e918&amp;fileName=D5290C00005-Protocol.pdf&amp;versionIdentifier=

MEDLEY Protocol

https://filehosting-v2.pharmacm.com/api/Attachment/Download?tenantId=80217111&amp;parentIdentifier=D5290C00005&amp;attachmentIdentifier=1ed84f06-335c-4887-8739-15ccaa840cb3&amp;fileName=D5290C00005-SAP.pdf&amp;versionIdentifier=

Statistical Analysis Plan (SAP)

Other Identifiers

2019-000201-69

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

D5290C00005

Identifier Type: -

Identifier Source: org_study_id