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

Respiratory Syncytial Virus Infections Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03959488
• Other study ID #: D5290C00005
• Secondary ID: 2019-000201-69
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: July 30, 2019
• Est. completion date: January 20, 2023

Study information

• Verified date: September 2023
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 925
• Est. completion date: January 20, 2023
• Est. primary completion date: May 3, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 0 Years to 1 Year

Eligibility

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

Related Conditions & MeSH terms

• Communicable Diseases
• Infections
• Respiratory Syncytial Virus Infections
• Virus Diseases

Intervention

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

Locations

Country	Name	City	State
Austria	Research Site	Graz
Belgium	Research Site	Bruxelles
Belgium	Research Site	Gent
Bulgaria	Research Site	Montana
Bulgaria	Research Site	Pazardzhik
Bulgaria	Research Site	Pleven
Bulgaria	Research Site	Plovdiv
Bulgaria	Research Site	Plovdiv
Bulgaria	Research Site	Ruse
Bulgaria	Research Site	Sliven
Bulgaria	Research Site	Sofia
Bulgaria	Research Site	Sofia
Bulgaria	Research Site	Veliko Tarnovo
Canada	Research Site	Edmonton	Alberta
Canada	Research Site	Vancouver	British Columbia
Czechia	Research Site	Praha 4
Estonia	Research Site	Tallinn
Estonia	Research Site	Tartu
Finland	Research Site	Tampere
France	Research Site	Amiens Cedex 1
France	Research Site	Bordeaux
France	Research Site	Brest
France	Research Site	Bron
France	Research Site	Caen
France	Research Site	Creteil Cedex
France	Research Site	Grenoble Cedex 9
France	Research Site	Marseille
France	Research Site	Pau Cedex
Germany	Research Site	Frankenthal
Germany	Research Site	Leipzig
Germany	Research Site	Mannheim
Hungary	Research Site	Baja
Hungary	Research Site	Budapest
Hungary	Research Site	Debrecen
Hungary	Research Site	Kecskemét
Hungary	Research Site	Miskolc
Italy	Research Site	Pisa
Italy	Research Site	Verona
Japan	Research Site	Fukui-shi
Japan	Research Site	Fukuoka-shi
Japan	Research Site	Kitakyusyu-shi
Japan	Research Site	Maebashi-shi
Japan	Research Site	Saitama shi
Japan	Research Site	Setagaya-ku
Korea, Republic of	Research Site	Ansan-si
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Suwon-si
Latvia	Research Site	Jekabpils
Latvia	Research Site	Riga
Latvia	Research Site	Riga
Lithuania	Research Site	Kaunas
Lithuania	Research Site	Kaunas
Mexico	Research Site	Cuernavaca
Mexico	Research Site	Mexico
New Zealand	Research Site	Christchurch
Poland	Research Site	Bydgoszcz
Poland	Research Site	Gdansk
Poland	Research Site	Krakow
Poland	Research Site	Kraków
Poland	Research Site	Wroclaw
Russian Federation	Research Site	Kazan
Russian Federation	Research Site	Novosibirsk
Russian Federation	Research Site	Perm
Russian Federation	Research Site	Saint Petersburg
Russian Federation	Research Site	Saint Petersburg
Russian Federation	Research Site	St Petersburg
Russian Federation	Research Site	Yaroslavl
South Africa	Research Site	Cape Town
South Africa	Research Site	Cape Town
South Africa	Research Site	Johannesburg
South Africa	Research Site	Johannesburg
South Africa	Research Site	Pretoria
South Africa	Research Site	Pretoria
South Africa	Research Site	Soweto
Spain	Research Site	Alicante
Spain	Research Site	Boadilla del Monte
Spain	Research Site	Elche
Spain	Research Site	Leganes
Spain	Research Site	Lleida
Spain	Research Site	Madrid
Spain	Research Site	Malaga
Spain	Research Site	Pozuelo de Alarcon
Spain	Research Site	Sant Cugat del Valles
Spain	Research Site	Tarragona
Sweden	Research Site	Stockholm
Turkey	Research Site	Adana
Turkey	Research Site	Izmir
Turkey	Research Site	Kocaeli
Ukraine	Research Site	Chernivts?
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
United Kingdom	Research Site	Leicester
United Kingdom	Research Site	London
United Kingdom	Research Site	Nottingham
United States	Research Site	Anaheim	California
United States	Research Site	Atlanta	Georgia
United States	Research Site	Aurora	Colorado
United States	Research Site	Charlottesville	Virginia
United States	Research Site	Chicago	Illinois
United States	Research Site	Cincinnati	Ohio
United States	Research Site	Colorado Springs	Colorado
United States	Research Site	Columbia	Missouri
United States	Research Site	Columbus	Ohio
United States	Research Site	Corpus Christi	Texas
United States	Research Site	Durham	North Carolina
United States	Research Site	Greenville	North Carolina
United States	Research Site	Greenville	South Carolina
United States	Research Site	Indianapolis	Indiana
United States	Research Site	Jackson	Mississippi
United States	Research Site	Layton	Utah
United States	Research Site	Long Beach	California
United States	Research Site	Los Angeles	California
United States	Research Site	Louisville	Kentucky
United States	Research Site	Mineola	New York
United States	Research Site	Morgantown	West Virginia
United States	Research Site	National City	California
United States	Research Site	Paramount	California
United States	Research Site	Saint George	Utah
United States	Research Site	Seattle	Washington
United States	Research Site	South Bend	Indiana
United States	Research Site	Syracuse	New York
United States	Research Site	Washington	District of Columbia
United States	Research Site	West Covina	California
United States	Research Site	West Des Moines	Iowa

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

United States,  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, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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

External Links

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