Stopping rules have been defined and will be applied in order to protect the study participants from unnecessary exposure to the monoclonal antibody, should the safety profile prove unacceptable in this population. Unblinded interim exploratory (as this trial is proof-of-concept, no flexible alpha spending function approach will be employed) analyses are planned when the last infant of each study arm will have completed 28 days of follow-up since the first dose of bNAb(s) (individually administered or in combination). These analyses may lead to stop enrolment of subsequent dose arms, adjustment of doses or of the second bNAbs administration.
the study investigators will pause the study for evaluation and will request that a DSMB review be performed within 7 days since the event occurrence. The DSMB will decide what additional data they would like to see and advise the study investigators on how to proceed. DSMB may decide on premature termination of some dose/arms (not of the trial); the decision may apply to either the CAP256V2LS or the VRC07-523LS arms (to each single dose/arm) and considers the occurrence in the CAP256V2LS arms independent of that in the VRC07-523LS arms. If the DSMB decides that further enrolment or administration cannot be continued, the study will stop accrual or administration but continue safety follow-up of all enrolled infants.
Missing data/loss to follow-up
All reasonable efforts will be taken to minimise loss to follow-up, which is expected to be minimal as data collection for primary and secondary endpoints. Contact details recording and tracking systems are in place to ensure a low rate of lost in the study; in addition, in the sample size calculation, we allowed for a 25% of loss to follow-up. The number and percentage of participants with complete follow-up information at day 28 and at 6 months, since first or second dose of bNAbs administration (alone or in combination), will be reported.
Roles and responsibilities
Coordinating Investigators
Ameena Goga (AG)
HIV and other Infectious Diseases Research Unit
South African Medical Research Council (SAMRC)
1 Soutpansberg Road
Arcadia, Private bag X 385001
Pretoria, South Africa (SA)
Phone: +27 12 3398524
E-mail: [email protected]
Gabriella Scarlatti (GS)
Viral Evolution and Transmission Unit
Ospedale San Raffaele srl. (OSR)
Via Olgettina 60
20132 Milan, Italy
Phone: +39 02 2643 4906
E-mail: [email protected]
Co-investigators
Philippe Van de Perre, INSERM/Univ Montpellier/EFS, France
Penny Moore, Wits Health Consortium (Pty) Ltd (WHC), SA
Thorkild Tylleskär (TT), Universitetet i Bergen, Norway
Overall project management
Stefania Dispinseri (SD), OSR, Italy
Trisha Ramraj (TR), SAMRC, SA
Kubashni Woeber, SAMRC, SA (Central Laboratory coordination in SA)
Statistician and Data Management
Tarylee Reddy, SAMRC, SA (Chief statistician)
Ishen Seocharan, SAMRC, SA (Data manager)
Clinical Team at Chatsworth Clinical Research Site (CRS)
Logashvari Naidoo (LN), SA (Principal Investigator)
Nitesha Jeenarain, SA (Site CRS leader)
Mayuri Reddy and Tamon Cafun-Naidoo, SA (Pharmacists)
Emma Clarence (Pediatrician and sub-investigator)
Researchers
Terusha Chetty, SAMRC, SA
Reshmi Dassaye, SAMRC, SA
Brodie Daniels, SAMRC, SA
Nobubelo Ngandu, SAMRC, SA
Carol Crowther, WHC, SA
Jean-Pierre Moles, INSERM/Univ Montpellier/EFS, France
Nicolas Nagot, INSERM/Univ Montpellier/EFS, France
Yoann Cazaubon, Univ Montpellier, France
This trial is sponsored by the South African Medical Research Council (SAMRC), PO Box 19070, Tygerberg, 7505, Francie van Zijl Drive, Parow Valley, Cape Town, Telephone: 021 938 0911, www.samrc.ac.za.
Study sponsor and funders do not have any role in study design; collection, management, analysis, and interpretation of data; writing of the report; and the decision to submit the report for publication .
ETHICS AND DISSEMINATION
A rigorous ethical and regulatory approval process specified by the national and institutional regulation will be followed. SAHPRA (South African Health Products Regulatory Authority) notification of approval is required before participants can be enrolled in this study.
As per South African Good Clinical Practice Guidelines (SA-GCPs), the G-EthicsHR, and the G-GPHlthCare, the informed consent form (ICF) and patient information sheet(s) are essential documents that will be reviewed and approved by the SAMRC Human Research Ethics Committee (HREC), an accredited ethics committee (EC) based in South Africa and provided to SAHPRA with the clinical trial application.
Protocol amendments will follow the same procedure. The study will be implemented after consultation and buy-in from the Chatsworth CRS Community Working Group (CWG). These discussions commenced in 2020, and updates will continue throughout study implementation.
Consent or assent
Written informed consent for study participation will be obtained before any study related procedures are performed. Mothers will be consented and screened prior to delivery or shortly after delivery of their infants, but randomization of the mother-infant pair will not proceed until the infant eligibility criteria have been confirmed. According to the SA-GCPs, the ICF and any patient information sheet(s) should be written in English and in the vernacular language that the participant is able to understand. Thus, we will provide information to the participants in a language that the participant understands and in a manner that takes into account the participant’s level of literacy, understanding, values, and personal belief systems. The Coordinator or a person designated by the PI will provide research study information to the participant and/or his/her legal representative(s), or guardian(s). The ICF content will be briefly and clearly presented, without coercion or unduly influencing a potential participant to enroll in the clinical trial. The original signed informed consent documents (ICF) will be retained by the investigator and a copy will be given to the participant for his/her record.
The current v4.0 dated 15 March 2024 Protocol, with its ICF and PIS, has been approved by SAHPRA and by the SAMRC HREC on Apr 23, 2024. Relevant changed to previous protocol versions are listed in Appendices (table 1).
The study has also been notified and approved by the Institutional Review Board of the Montpellier University Hospital, Montpellier, France on March 3, 2022; by the Ethics Committee of the San Raffaele Hospital, Milan, Italy on May 11, 2022; and by the Regional Committee for Medical and Healthcare Research Ethics (REK) north, Norway on December 12, 2022.
Dissemination policy
The study team will disseminate the trial results by sharing the results with the CWG, with the scientific community at national and international conferences, through peer-reviewed journal publications, and by sharing results with policy makers nationally, and with the World Health Organization.