| Protocol No: | ECCT/23/12/02 | Date of Protocol: | 30-06-2023 |
| Study Title: | Phase III, randomized, observer-blind, placebo-controlled, multi-center, multinational study to evaluate the efficacy, immunogenicity, and safety of a Respiratory Syncytial Virus vaccine in infants and toddlers (PEARL) |
| No Change | |
| Study Objectives: | Primary Objective Efficacy 1. To demonstrate the clinical efficacy of RSVt vaccine for the prevention of RT-PCR confirmed RSV LRTD after 2 doses, over RSV Season 1. Secondary Objective Efficacy 1. To demonstrate the clinical efficacy of RSVt vaccine for the prevention of RT-PCR confirmed RSV URTD after2 doses over RSV Season† 1 2. To demonstrate the clinical efficacy of RSVt vaccine for the prevention of RT-PCR confirmed RSV associated with the occurrence of LRTD, leading to hospitObjectives Endpoints 3. To describe the clinical efficacy of RSVt vaccine for the prevention of RT-PCR confirmed RSV severe LRTD after 2 doses over RSV Season 1 4. To describe the clinical efficacy of RSVt vaccine for the prevention of RT-PCR confirmed RSV LRTD after 2 doses over RSV Season 1, necessitating urgent care 5. To describe the clinical efficacy of RSVt vaccine for the prevention of RT PCR confirmed RSV ARD after 2 doses over RSV Season 1 6. To describe the clinical efficacy of RSVt vaccine for the prevention of RT-PCR confirmed RSV ARD after 2 doses over RSV Season 1, leading to hospitalization 7. To describe the clinical efficacy of RSVt vaccine for the prevention of RT-PCR confirmed RSV ARD after 2 doses over RSV Season 1, necessitating urgent care 8. To describe the clinical efficacy of RSVt vaccine for the prevention of RT-PCR confirmed RSV LRTD, by RSV strain after 2 doses over RSV Season 1 9. To describe the clinical efficacy of RSVt vaccine for the prevention of RT-PCR confirmed RSV URTD, by RSV strain after 2 doses over RSV Season 1 10. To describe the clinical efficacy of RSVt vaccine for the prevention of RT-PCR confirmed RSV ARD, by RSV strain after 2 doses over RSV Season 1 11. To describe the clinical efficacy of RSVt vaccine for the prevention of RT-PCR confirmed RSV LRTD after at least one dose, over RSV Season 1 12. To describe the clinical efficacy of RSVt vaccine for the Pharmaceutical form Route of administration Composition, apart from active substance(s) Is it otherwise identical to the INDP? If not, specify major ingredients 1 Liquid for nasal spray Intranasal Histidine-based formulation buffer (including monosodium glutamate, sodium chloride and L-histidine) Yes prevention of RT-PCR confirmed RSV URTD after at least one dose, over RSV Season 1 13. To describe the clinical efficacy of RSVt vaccine for the prevention of RT-PCR confirmed RSV ARD after at least one dose, over RSV Season 1 14. To describe the clinical efficacy of RSVt vaccine for the prevention of RT-PCR confirmed RSV LRTD after 2 doses over RSV Season 2 15. To describe the clinical efficacy of RSVt vaccine for the prevention of RT-PCR confirmed RSV URTD after 2 doses over RSV Season 2 16. To describe the clinical efficacy of RSVt vaccine for the prevention of RT-PCR confirmed RSV ARD after 2 doses over RSV Season 2 Safety 17. To describe the safety profile of the RSVt vaccine Immunogenicity 18. To describe the RSV A and B serum neutralizing and RSV serum anti-F IgA and IgG antibody responses to the study intervention Exploratory Efficacy Efficacy 1. To describe the clinical efficacy of RSVt vaccine for the prevention of RT-PCR confirmed RSV URTD after 2 doses over RSV Season 1, leading to outpatient medical care, urgent care, or hospitalization. 2. To describe the clinical efficacy of RSVt vaccine for the prevention of RT-PCR confirmed RSV URTD after 2 doses over RSV Season 1, leading to outpatient medical care 3. To describe the clinical efficacy of RSVt vaccine for the prevention of RT-PCR confirmed RSV ARD after 2 doses over RSV Season 1, leading to outpatient medical care 4. To describe the clinical efficacy of RSVt vaccine for the prevention of RT-PCR confirmed RSV LRTD after 2 doses over RSV Season 2, leading to hospitalization 5. To describe the clinical efficacy of RSVt vaccine for the prevention of RT-PCR confirmed RSV severe LRTD after 2 doses over RSV Season 2 6. To describe the clinical efficacy of RSVt vaccine for the prevention of RT-PCR confirmed RSV ARD after 2 doses over RSV Season 2, leading to hospitalization 7. To describe the clinical efficacy of RSVt vaccine for the prevention of all-cause acute otitis media (AOM) after 2 doses over RSV Season 1 and Season 2. Long-Term Immunogenicity 8. To describe the RSV A and B serum neutralizing and RSV serum anti-F IgA and IgG antibody responses to the study intervention at 3 months, 6 months, 1 year and 1.5 years after dose 2 Immunogenicity 9. To estimate an immunological correlate of protection against RT-PCR confirmed RSV LRTD Safety 10. To assess the evidence of vaccine-enhanced RSV disease upon natural infection during both RSV Season 1 and RSV Season 2 10. Presence of Grade 1, 2, and 3 LRTD or ARD episodes (during both RSV Season 1 and RSV Season 2) associated with any RT-PCR confirmed RSV strain Other 11. To describe in each study intervention group the following events that are associated with cases of RT-PCR confirmed RSV ARD, associated with any RSV strain, over Season 1: ▪ recurrent wheezing ▪ pneumonia ▪ bronchiolitis ▪ AOM ▪ febrile illness |
| 1 | Secondary Objective 14. To describe the clinical efficacy of RSVt vaccine for the prevention of RT -PCR confirmed RSV LRTD after 2 doses over RSV Season 1, in RSV-exposed participants 15. To describe the clinical efficacy of RSVt vaccine for the prevention of RT -PCR confirmed RSV URTD after 16. To describe the clinical efficacy of RSVt vaccine for the prevention of RT PCR confirmed RSV ARD after 2 doses over RSV Season 1, by baseline serostatus 2 doses over RSV Season 1, by baseline serostatus 20. To describe the clinical efficacy of RSVt vaccine for the prevention of RT-PCR confirmed RSV LRTD after 2 doses over RSV Season 2, by baseline serostatus 21. To describe the clinical efficacy of RSVt vaccine for the prevention of RT-PCR confirmed RSV URTD after 2 doses over RSV Season 2, by baseline serostatus 22. To describe the clinical efficacy of RSVt vaccine for the prevention of RT-PCR confirmed RSV ARD after 2 doses over RSV Season 2, by baseline serostatus. |
| Laymans Summary: | Respiratory Syncytial Virus (RSV) is a contagious virus (germ) that circulates particularly during the winter months and throughout the year in some parts of the world. It is transmitted through droplets containing the virus when someone infected sneezes or coughs. In most infants, the RSV infection will be a mild illness similar to a cold, with symptoms such as fever, runny nose, sore throat, ear infection, cough, and croup (barky cough with hoarseness). In some cases, RSV can cause serious lung illnesses such as pneumonia and bronchiolitis (an infection of small airways in the lung called bronchioles), which may lead to hospitalization. At this time, there is no approved vaccine to prevent RSV illness. Sanofi Pasteur is developing a vaccine called the RSVt vaccine. The study is called VAD00004 and is a Phase III trial, with two study arms, multiple research sites in multiple countries. in Kenya there are a total of 7 sites. It will be conducted in infants and toddlers 6 months to less than 22 months of age to evaluate if the vaccine works, how safe it is and how the human body responds to protect itself following vaccination of 2 intranasal spray of RSVt vaccine. The trial is designed to demonstrate how the vaccine works in preventing the occurrence of respiratory syncytial Virus. The investigational RSVt vaccine in this study contains a live, weakened form of the virus (that is, attenuated) and is given as a nasal spray. It is made to help a person’s body respond in a way that will protect them from getting sick from the virus. The vaccine has been tested in humans before, and other live attenuated RSV vaccines very similar to this one has also been tested in both adults and children. A total of 6300 children are planned to be enrolled worldwide. Eligible participants will be randomized in a 1:1 ratio to receive 2 intranasal administrations 56 days apart of either the RSVt vaccine or placebo at day 1 and day 57 of the study. Additional illness visits may occur during the study for those who develops RSV like symptoms. Each participant will be followed for 24 months in the study. It is anticipated that approximately 1500 participants could be enrolled by local sites in Kenya. The trial will target recruitment of people from different races and ethnic groups that at a minimum will be representative of the countries in which the trial will be conducted. |
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| Abstract of Study: | Respiratory syncytial virus (RSV) is the most important cause of severe acute lower respiratory illness in infants and children and the most common cause of severe pneumonia requiring hospital admission in children worldwide. According to global estimates, RSV caused approximately 33 million cases of lower respiratory illness and approximately 118,000 deaths in children < 5 years of age in 2015.Infants and young children are at increased risk for RSV infections because of their maturing immune system and lack of prior exposure to RSV. A genetically stable live-attenuated RSV ΔNS2/Δ1313/I1314L vaccine has been shown to be safe and immunogenic in RSV-seronegative children in Phase I studies with further research ongoing in RSV-seropositive children. Sanofi is conducting clinical studies with a similar RSV ΔNS2/Δ1313/I1314L vaccine, referred to as RSVt vaccine, as part of the Phase III development of the RSVt vaccine (the VAD00004 study). The VAD00004 study, is a Phase III, randomized, observer-blind, placebo-controlled, multi-center, multinational study to evaluate the efficacy, immunogenicity, and safety of a Respiratory Syncytial Virus vaccine in infants and toddlers. The study is designed to evaluate the efficacy, immunogenicity, and safety of RSVt vaccine administered by intranasal route and compared to placebo. Overall, a global sample size of approximately 6300 participants 6 months to < 22 months of age will be enrolled in the study. Kenya site will enroll approximately 1500 participants. Eligible participants will be randomized in a 1:1 ratio to receive 2 intranasal administrations of either the RSVt vaccine or placebo.Study duration will be 24months for each participant. The safety evaluation will start after the first vaccination and up to the end of the study. The trial will target recruitment of people from different races and ethnic groups that at a minimum will be representative of the countries in which the trial will be conducted. |
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