Clinical trial NCT06042049: A Study to Assess Safety, Pharmacokinetics Anti-Drug Antibody and Anti-RSV Antibody After 2 Doses of Nirsevimab
Official title: A Phase III Single-Arm Open-Label Study to Evaluate the Safety PK ADA and Anti RSV nAb Following Administration of 2 Doses of Nirsevimab Given 5 to 6 Months Apart in Infants With CHD, CLD, Immunocompromise, Down Syndrome, or Born Pre-Term in Japan
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Respiratory Syncytial Virus Infections
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: Iqvia Pty Ltd
First posted: 2023-09-18
Enrollment: 33
Sex: ALL
Minimum age (years): 0
Maximum age (years): 1
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to measure the safety, PK, occurrence of ADA to nirsevimab, and anti-RSV neutralizing Ab in Japanese children with certain health conditions or pre-term infants aged ≤12 months.

Study details include

* The study duration is approximately 21 months with a 2-month enrollment period.
* Study intervention is 2 doses administered 5- 6 months apart.
* The study has 5 or 6 site visits and several telephone contacts with a 2 or 4 week interval.


Eligibility criteria: Inclusion Criteria:

1. Written informed consent and any locally required authorization obtained from the participant's parent(s)/legally authorized representative(s) before performing any protocol-related procedures, including screening evaluations
2. Japanese infants of ≤12 months of age eligible to receive palivizumab in accordance with national or local guidelines and those who must meet at least one of the following conditions at the time of informed consent.

   1. Immunodeficiency
   2. Chronic Lung Disease
   3. Congenital Heart Disease
   4. Down syndrome
   5. Born pre-term ≤28 wks Gestation age and aged ≤12 months, or born pre-term \>28 wks and ≤35 wks Gestation age and aged ≤6 months
3. The participant's parent(s)/legally authorized representative(s) can understand and comply with the requirements of the protocol including follow-up visits as judged by the investigator.
4. The participant is available to complete the follow-up period for approximately 19 months, which will be approximately 1 year after receipt of 2nd dose of nirsevimab

Exclusion Criteria:

1. Requirement for mechanical ventilation, extracorporeal membrane oxygenation, continuous positive airway pressure (CPAP), or other mechanical respiratory or cardiac support at the time of enrollment
2. A current, active RSV infection at the time of screening and investigational product administration
3. Any fever (≥100.4°F \[≥38.0°C\], regardless of route) or acute illness at the time of prior to investigational product administration
4. Any serious concurrent medical condition (except those resulting in an immune deficiency condition), including:

   1. Known renal impairment
   2. Known hepatic dysfunction including known or suspected active or chronic hepatitis infection
   3. Any seizure disorder or evolving or unstable neurological condition
5. Anticipated cardiac surgery within 5-6 months after enrollment
6. Prior history of a suspected or actual acute life-threatening event
7. Receipt or intended use of palivizumab in the current enrollment season
8. Any known allergy or history of allergic reaction to any component of nirsevimab
9. Any known allergy or history of allergic reaction to immunoglobulin products, blood products, or other foreign proteins
10. Concurrent enrollment in another interventional study, or prior receipt of any investigational agent
11. Anticipated survival of less than 1 year at the time of informed consent
12. Any condition that, in the opinion of the investigator, would interfere with the evaluation of the investigational product or interpretation of study results
13. 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

Primary outcomes:
measure: Incidence of all TEAEs, TESAEs, AESIs, and NOCDs
timeFrame: 360 days after the 2nd or last dose administered in the study
measure: Study discontinuations prior to Day 151 post 2nd dose.
timeFrame: 360 days after the 2nd or last dose administered in the study
Secondary outcomes:
measure: Pharmacokinetics (PK) - Nirsevimab serum concentrations
timeFrame: 360 days after the 2nd or last dose administered in the study
measure: ADA - Occurrence of ADA to nirsevimab in serum
timeFrame: 360 days after the 2nd or last dose administered in the study
measure: Anti-RSV neutralizing Ab - Anti-RSV neutralizing Ab levels (IU/mL) in serum
timeFrame: 360 days after the 2nd or last dose administered in the study
Other outcomes:
measure: MA-RSV LRTI - Occurrence of MA-LRTI (inpatient and outpatient) due to RT-PCR-confirmed RSV
timeFrame: through 150 and 360 days post 2nd dose
measure: MA-RSV LRTI - Occurrence of hospitalizations due to RT-PCR-confirmed RSV
timeFrame: through 150 and 360 days post 2nd dose
measure: Monitoring for RSV Resistance - Genotypic analysis of the F protein from collected RSV-positive respiratory secretion specimens
timeFrame: through 150 and 360 days post 2nd dose
measure: Monitoring RSV Resistance to Nirsevimab - RSV novel variants will be phenotypically characterized for nirsevimab susceptibility
timeFrame: through 150 and 360 days post 2nd dose
Locations:
city: Bunkyo-ku
country: Japan
facility: Research Site
city: Fuchu-shi
country: Japan
facility: Research Site
city: Fukuoka-shi
country: Japan
facility: Research Site
city: Kitakyusyu-shi
country: Japan
facility: Research Site
city: Koto-ku
country: Japan
facility: Research Site
city: Kurume-shi
country: Japan
facility: Research Site
city: Nagasaki-shi
country: Japan
facility: Research Site
city: Saitama-shi
country: Japan
facility: Research Site
city: Yokohama-shi
country: Japan
facility: Research Site
Study officials:
References: