Pan African Clinical Trials Registry
South African Medical Research Council, South African Cochrane Centre
PO Box 19070, Tygerberg, 7505, South Africa
Telephone: +27 21 938 0506 / +27 21 938 0834 Fax: +27 21 938 0836
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR202311725768030 Date of Approval: 01/11/2023
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title Efficacy, Immunogenicity, and Safety Study of a Respiratory Syncytial Virus Vaccine in Infants and Toddlers
Official scientific 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)
Brief summary describing the background and objectives of the trial The investigational RSV NS2/1313/I1314L vaccine, developed at the Laboratory of Infectious Diseases at the National Institute of Allergy and Infectious Diseases (referred to as the NIH RSV NS2/1313/I1314L vaccine) is based on an attenuation approach involving the deletion of the gene encoding the RSV IFN / apoptosis antagonist NS2 protein (NS2). Deletion of NS2 gene attenuates the virus and may enhance immunogenicity. RSVt vaccine additionally contains a genetically stabilized attenuating and temperature sensitivity mutation in the L protein (codon deletion 1313, as well as a missense mutation I1314L that prevents a de-attenuating mutation that otherwise can occur at position 1314). The RSVt vaccine temperature sensitivity translates into a shut-off of virus replication at 38ºC-39°C. Temperature sensitivity is thought to restrict vaccine virus replication to the upper respiratory tract, increasing vaccine safety. Sanofi’s investigational live-attenuated RSV NS2/1313/I1314L vaccine (hereafter referred to as RSVt vaccine) is the same construct as the NIH RSV NS2/1313/I1314L vaccine. The vaccines differ in formulation and mode of intranasal administration. The RSVt vaccine is being developed for the pediatric population. Objectives: 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 2. To demonstrate the clinical efficacy of RSVt vaccine for the prevention of RT PCR confirmed RSV URTD after 2 doses over RSV Season† 1 3. To demonstrate the clinical efficacy of RSVt vaccine for the prevention of RT-PCR confirmed RSV associated with the occurrence of LRTD, leading to hospitalization after 2 doses over RSV Season 1 4. 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 5. To describe the clinical efficacy of RSVt vaccine for the prevention of RT-PCR confirmed RSV LRTD after 2 doses over RSV
Type of trial RCT
Acronym (If the trial has an acronym then please provide) PEARL
Disease(s) or condition(s) being studied Infections and Infestations,Paediatrics,Respiratory
Sub-Disease(s) or condition(s) being studied Respiratory Syncytial Virus
Purpose of the trial Prevention: Vaccines
Anticipated trial start date 01/02/2024
Actual trial start date
Anticipated date of last follow up 28/02/2025
Actual Last follow-up date
Anticipated target sample size (number of participants) 1350
Actual target sample size (number of participants)
Recruitment status Not yet recruiting
Publication URL
Secondary Ids Issuing authority/Trial register
U1111 1280 7192 World Health Organization WHO universal trial number
22050 US Investigational New Drug IND number
2023 505762 29 CTIS EU Trial Number
STUDY DESIGN
Intervention assignment Allocation to intervention If randomised, describe how the allocation sequence was generated Describe how the allocation sequence/code was concealed from the person allocating the participants to the intervention arms Masking If masking / blinding was used
Parallel: different groups receive different interventions at same time during study Randomised Stratified allocation where factors such as age, gender, center, or previous treatment are used in the stratification Central randomisation by phone/fax Masking/blinding used Care giver/Provider,Participants
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group RSVt vaccine 2 intranasal administrations 56 days apart Twice Active Vaccine 675
Control Group Placebo 2 intranasal administrations 56 days apart Twice Placebo 675 Placebo
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
1. Aged 6 months to < 22 months on the day of inclusion 2. Participants who are healthy as determined by medical evaluation including medical history. 3. Born at full term of pregnancy (≥ 37 weeks) or born after a gestation period of 27 through 36 weeks and medically stable as assessed by the investigator, based on the following definition: “Medically stable” refers to the condition of premature infants who do not require significant medical support or ongoing management for debilitating disease and who have demonstrated a clinical course of sustained recovery by the time they receive the first dose of study intervention 4. Informed consent form has been signed and dated by the parent(s) or other LAR (and by an independent witness if required by local regulations) 5. Participant and parent(s)/LAR are able to attend all scheduled visits and to comply with all study procedures 1. Known or suspected congenital or acquired immunodeficiency; or receipt of immunosuppressive therapy, such as anti-cancer chemotherapy or radiation therapy, within the preceding 6 months; or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months) 2. Known systemic hypersensitivity to any of the study intervention components, or history of a life-threatening reaction to the study intervention used in the study or to a product containing any of the same substances 3. Chronic illness that, in the opinion of the investigator, is at a stage where it might interfere with study conduct or completion 4. History of medically diagnosed wheezing 5. Any acute febrile illness in the past 48 hours that according to investigator judgment is significant enough to interfere with successful inoculation on the day of vaccination. A prospective participant should not be included in the study until the condition has resolved or the febrile event has subsided. 6. Probable or confirmed ongoing case of viral respiratory infection (including COVID-19, influenza, rhinovirus, etc.) at the time of enrollment. A prospective participant should not be included in the study until the respiratory infection has resolved. 7. Member of a household that contains an immunocompromised individual, including, but not limited to: • a person who is HIV infected • a person who has received chemotherapy within the 12 months prior to study enrollment • a person who has received (within the past 6 months) or is receiving (at the time of enrollment) immunosuppressant agents • a person living with a solid organ or bone marrow transplant Infant: 13 Month(s)-24 Month(s) 6 Month(s) 22 Month(s) Both
ETHICS APPROVAL
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 28/09/2023 Jaramogi Oginga Odinga Teaching and Referral Hospital. JOOTRH
Ethics Committee Address
Street address City Postal code Country
Jomo Kenyatta Highway Kaloleni Kisumu KE, Central, Kenya Kisumu 40100 Kenya
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 31/08/2023 Kintampo Health Research Centre Institutional Ethics Committee
Ethics Committee Address
Street address City Postal code Country
P.O BOX 200 KINTAMPO, BRONG AHAFO REGION Kintampo . Ghana
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Occurrence of LRTD (during RSV Season 1) associated with any RT PCR confirmed RSV strain > 21 days post dose 2 21 days post dose
Secondary Outcome Occurrence of URTD (during RSV Season 1) associated with any RT PCR confirmed RSV strain > 21 days post-dose 2 21 days post dose
Secondary Outcome Occurrence of LRTD (during RSV Season 1) associated with any RT PCR confirmed RSV strain leading to hospitalization > 21 days post-dose 2 21 days post dose
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
University of Health and Allied Sciences UHAS Dr Kokou Amegan-Aho, University of Health and Allied Sciences UHAS, PMB31 Ho Ghana
Kintampo Health Research Centre Dr Seyram Kaali, Kintampo Health Research Centre, Ministry of Health, NO2 Health Loop, Kintampo Kintampo Ghana
Dodowa Health Research Centre Dr. Alberta Amu, Dodowa Health Research Centre, AZ 820 Hospital Street Dodowa Ghana
Kumasi Centre for Collaborative Research in Tropical Medicine KCCR Dr John Amuasi, Kumasi Centre for Collaborative Research in Tropical Medicine KCCR, Kwame Nkrumah University of Science and Technology, PMB UPO South-end, Asuogya Road Kumasi Ghana
Navrongo Health Research Centre Dr Patrick Ansah, Navrongo Health Research Centre, Navrongo, Behind War Memorial Hospital Navrongo Ghana
Kenya Medical Research Institute KEMRI. Center for Disease Control Dr Simon Kariuki, KEMRI/CGHR, SIAYA, County Referral Hospital, KEMRI/CGHR, Off Kisumu-Busia Road Kisumu 40100 Kenya
Kenya Medical Research Institute CMR Kargeno Research and Policy Hub Dr Onono Maricianah, Junction of Ojijo-Karume road Opposite Upper railways Ap line dispensary Kisumu Kenya
Victoria Biomedical Research Institute Dr Lucas Otieno, Kisumu, Kenya, along Angawa Avenue, opposite Kenyatta Sports Ground Kisumu Kenya
KEMRI CCR Butere Clinical Research Centre Dr Janet Oyieko, Shaitsala-Sabatia Rd, Butere Butere Kenya
Kenya Medical Research Institute. United States Army Medical Research Directorate Dr Fredrick Sawe, Main Address Hospital Road Kericho Kenya
KEMRI SERU Kenya Medical Research Institute Scientific and Ethics Review Unit Dr Wria Walter Otieno, Off Kisumu Bondo Road, Opposite Kombewa County Hospital Kisimu Kenya
KAVI Institute of Clinical Research University of Nairobi Dr Walter Jaoko, Mbagathi Rd Nairobi Kenya
FUNDING SOURCES
Name of source Street address City Postal code Country
Sponsor Funding Sanofi Pasteur Inc. Discovery Drive Swiftwater PA 18370-018 United States of America
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Sanofi Pasteur Inc. Discovery Drive Swiftwater 18370-018 United States of America Commercial Sector/Industry
COLLABORATORS
Name Street address City Postal code Country
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Tsiri Agbenyega ccm2000a@yahoo.com +233208113848 Agogo Presbyterian Hospital
City Postal code Country Position/Affiliation
Agogo Ghana National Coordinator
Role Name Email Phone Street address
Scientific Enquiries Dayan Gustavo Gustavo.Dayan@sanofi.com +15709727826 1 Discovery Drive Swiftwater
City Postal code Country Position/Affiliation
Pennsylvania 18370 United States of America Senior Global Clinical Development Strategic Expert
Role Name Email Phone Street address
Public Enquiries Tsiri Agbenyega ccm2000a@yahoo.com +233208113848 Agogo Presbyterian Hospital
City Postal code Country Position/Affiliation
Agogo Ghana National Coordinator
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes At the end of the clinical study, the Sponsor may publish the study results in scientific journal(s). As part of the review for publication, independent scientists may need to use “coded” data of all the study participants to independently verify the study’s results. Sanofi shares information about clinical trials and results on publicly accessible websites, based on company commitments, international and local legal and regulatory requirements, and other clinical trial disclosure commitments established by pharmaceutical industry associations. These websites include ClinicalTrials.gov, euclinicaltrials.eu, and sanofi.com, as well as some national registries. For pediatric and adult trials, the results will generally be submitted/released 6 and 12 months respectively, after the end of the clinical trial worldwide (ie, the last active, participating country). In addition, results from clinical trials in patients are required to be submitted to peer reviewed journals following internal company review for accuracy, fair balance, and intellectual property. For those journals that request sharing of the analyzable data sets that are reported in the publication, interested researchers are directed to submit their request to vivli.org. Individual anonymized participant data and supporting clinical documents are available for request at vivli.org. While making information available we continue to protect the privacy of participants in our clinical trials. Details on data sharing criteria and process for requesting access can be found at this web address: vivli.org. Clinical Study Report,Informed Consent Form,Statistical Analysis Plan,Study Protocol The aggregate results of any conducted research will be available in accordance with the effective Sanofi policy on study data publication. Government or other health research databases, researchers, government agencies, companies, or other groups that are not participating in this study
URL Results Available Results Summary Result Posting Date First Journal Publication Date
No
Result Upload 1: Result Upload 2: Result Upload 3: Result Upload 4: Result Upload 5:
Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information