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.: PACTR202308483453792 Date of Approval: 11/08/2023
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title SAMBULELO, a phase II double blind randomised placebo-controlled clinical trial to evaluate the safety & pharmacokinetics of VRC07-523LS in breastfed HIV-exposed uninfected and HIV-infected neonates and infants in South Africa.
Official scientific title Phase II double blind randomised placebo-controlled clinical trial to evaluate the safety & pharmacokinetics ofVRC07-523LS in breastfed HIV-exposed uninfected and HIV-infected neonates and infants in South-Africa
Brief summary describing the background and objectives of the trial Despite the deployment of lifelong universal triple antiretroviral therapy (ART) in HIV-infected pregnant and breastfeeding mothers (Option B+), since 2013, it is estimated that 180,000 new paediatric HIV infections occurred during the year 2017 alone (UNAIDS 2018). Understanding how best to manage these infections and how to eliminate paediatric HIV reservoirs, to achieve paediatric functional HIV cure is critical (Technau 2017and 2018). These residual transmissions, as high as 12-15% at 18 months are still common in many settings. Itis estimated that at least half of this residual transmission is attributable to breastfeeding (BF) as a result of lateinitiation of maternal ART during pregnancy or BF, lack of maternal adherence to ART, incomplete PMTCTcascade (no HIV testing, no ART initiation), cell-associated HIV transmission by BF [12 months MTCT rate2.4% (Rollins 2012) or 2.9% (Bispo, 2017)] or acquisition of maternal HIV infection during pregnancy or breastfeeding (Pintye, 2018, Dinh 2015). Consequently, complementary interventions are needed to attain the paediatric HIV elimination target, and possibly also to optimise management of HIV-infected children. Strategies such as infant PrEP (Van de Perre, 2017) and infant passive immune prophylaxis (Pegu, 2017) maybe particularly useful as these do not rely solely on maternal adequate adherence or response to ART. Primary objectives: 1. To evaluate the safety up to age 12 weeks of a single subcutaneous (SC) injection of VRC07-523LS, administered within 72 hours of birth in HIV exposed uninfected (HEU) breastfeeding infants (Group 1) and newly diagnosed HIV-infected breastfeeding infants (Group 3). 2. To determine the pharmacokinetics up to age 12 weeks of a single perinatal SC injection of VRC07-523LS, in HEU breastfeeding infants (Group 1) and newly diagnosed HIV-infected breastfeeding infants (Group 3).
Type of trial RCT
Acronym (If the trial has an acronym then please provide)
Disease(s) or condition(s) being studied Infections and Infestations
Sub-Disease(s) or condition(s) being studied HIV/AIDS
Purpose of the trial Prevention
Anticipated trial start date 01/02/2023
Actual trial start date
Anticipated date of last follow up 28/02/2026
Actual Last follow-up date
Anticipated target sample size (number of participants) 129
Actual target sample size (number of participants)
Recruitment status Not yet recruiting
Publication URL
Secondary Ids Issuing authority/Trial register
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 Simple randomization using a randomization table created by a computer software program Allocation was determined by the holder of the sequence who is situated off site Masking/blinding used Participants
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group VRC07523LS 80mg subcutaneous (SC)VRC07-523LS within 72hours of birth and if still breastfeeding, 100mg SCVRC07-523LS at 12 weeks post-delivery 80mg subcutaneous (SC)VRC07-523LS within 72hours of birth and if still breastfeeding, 100mg SCVRC07-523LS at 12 weeks post-delivery VRC07-523LS is a broadly neutralizing human mAb targeted against the HIV-1CD4 binding site. It was developed by VRC/NIAID/NIH and produced in a Chinese Hamster Ovary (CHO)DG44 cell line in accordance with the cGMP regulations at the VRC Pilot Plant operated under contract by the Vaccine Clinical Materials Program, Leidos Biomedical Research,Frederick, MD. 65
Experimental Group VRC07523LS 80mg SC Placebo within 72hours of birth and if still breastfeeding, 100mg SC Placebo at 12 weeks post-delivery 80mg SC Placebo within 72hours of birth and if still breastfeeding, 100mg SC Placebo at 12 weeks post-delivery VRC07-523LS is a broadly neutralizing human mAb targeted against the HIV-1CD4 binding site. It was developed by VRC/NIAID/NIH and produced in a Chinese Hamster Ovary (CHO)DG44 cell line in accordance with the cGMP regulations at the VRC Pilot Plant operated under contract by the Vaccine Clinical Materials Program, Leidos Biomedical Research, Frederick, MD. 44
Experimental Group VRC07523LS 80mg SC VRC07-523LS within 72 hours of birth 80mg SC VRC07-523LS within 72 hours of birth VRC07-523LS is a broadly neutralizing human mistargeted against the HIV-1CD4 binding site. It was developed by VRC/NIAID/NIH and produced in a Chinese Hamster Ovary (CHO)DG44 cell line in accordance with the cGMP regulations at the VRC Pilot Plant operated under contract by the Vaccine Clinical Materials Program, Leidos Biomedical Research, Frederick, MD. 10
Control Group Placebo 80mg SC Placebo within 72hours of birth 80mg SC Placebo within 72hours of birth The placebo for the VRC07-523LS mAb (VRC-PLAMAB068-00-AB) administered SC will either be manufactured at the VRC Pilot Plant operated by Leidos Biomedical Research, Inc., Frederick, or if no longer manufactured, then saline will be used. 10 Placebo
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
Eligibility criteria Maternal inclusion criteria 1) Documented HIV-1infection antenatally or at delivery and receiving ART as per national guidelines 2) Greater than or equal to18 years of age 3) Breastfeeding at the time of enrolment or willing to initiate breastfeeding in the immediate post-partum period INFANT ELIGIBILITY CRITERIA 1) Gestational age greater or equal to36 weeks, assessed using dual methods of early sonar AND birth Ballard Score (done up to 42 hours after birth) 2) Birth weight greater than or equal to 2.0 kg and lower than or equal to 4.5kg 3) Written consent of one or both parents (according to South African regulation) Mother exclusion criteria 1) Prior participation in anyHIV-1 vaccine trial 2) Receipt of another active or passive HIVimmunotherapy or investigational product concurrently 3) Documented or suspected serious medical illness with fatal compromise or immediate life-threatening condition (other than HIV-infection as judged by the examining clinician) 4) Unable or unwilling to provide a signed informed consent to participate to the study for herself and her infant 5) Known active tuberculosis or other opportunistic infection 6.Plan to relocate in 1 year or do not have a local address 7)Does not have her own cell phone 8)Not able to provide three alternate contact phone numbers 9) Multiple pregnancies, i.e. twins, triplets, quadruplets, etc. 10) Unwilling or unable to comply with the schedule of activity Infant exclusion criteria 1) Receipt of or anticipated need for blood product, immunoglobulin, or immunosuppressive therapy. This includes infants who require hepatitis immunoglobulins (HBIG) but not infants who receive hepatitis Bvaccine in the new-born period 2)Documented or suspected serious medical or immediate life-threatening condition 3) Infant in ICU or high care requiring supplemental oxygen at time of bNAb dose 4) Known allergy to study drug or components 5) Baseline laboratory results on all neonates -Hemoglobin level less than 12.0 g/dL- Platelet count less than 100,000cells/mm3 - Absolute neutrophil count: for infants less than 24 hours old, less than 4,000 cells/mm3; for infants greater than 24 hours old, less than1,250 cells/mm3 - Serum glutamic pyruvic transaminase (SGPT) (alanine aminotransferase ALT) greater than or equal to 1.25 times the upper limit of age-adjusted normal Infant: 0 Month-23Month 36 Week(s) 12 Month(s) Both Infant: 0 Month-23 Month 36 Week(s) 12 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 21/02/2023 SAMRC Ethics Committee
Ethics Committee Address
Street address City Postal code Country
Francie Van Zijl Drive, Parowvallei, 7505, Cape Town 7505 South Africa
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 14/07/2023 SAHPRA
Ethics Committee Address
Street address City Postal code Country
CSIR, Reception Building 38a, Meiring Naude Road, Brummeria Pretoria 0001 South Africa
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome SAE among group 1: this single-stage phase 2 trial relies on the demonstration that the proportion of infants (P) using VRC07-523LS will meet an expected low level or be free of SAE (p(1), the background level in the absence of bNAbs) which is higher than a second proportion level p(0), indicating that the safety level is unacceptable. This p(0) is the level under which we will reject the use of VRC07-LSfor safety issues. The trial tests the null hypothesisH0: P =p(0) against the alternative hypothesis H1: P>p(1). It sets an appropriate cut-off between p(0) and p(1), providing a critical number of participants without SAE which will be used to move on to a Phase 3 trial or not. 12 weeks after the first injection.
Secondary Outcome Among HIV-infected children, we will assess the virological success at 6 months post-delivery. We will adopt the same approach as primary endpoints for the evaluation of virological success in group 3,based on the single-stage A’Hern design. In this case, p(0) will be the minimum rate of children with virological success we can accept, and p(1) is the expected rate of children with virological success. Although some local data provide some indications on the potential value of p(0) (K. Technau Lancet HIVpaper), we will use group 4 to assess p(0) in the trial context, using a randomisation for group allocation to get very comparable groups 3 and 4. Although we want to make sure that the virological success rate will not be hampered by bNAbs, we expect an improvement in the response to treatment due to the early neutralization of HIV virions. This bNAbs activities expected to reduce the HIV RNA load, which is associated with a greater virological response at 6months post-ART initiation (ref). The trial tests the null hypothesis H0: P < p(0) against the alternative hypothesis H1: P > p(1) 6 months post-delivery
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Steve Biko Academic Hospital The Steve Biko Academic Hospital c/o SteveBiko and Malan Street, Capital Park, Pretoria 0001 South Africa
Rahima Moosa Mother and Child Hospital Corner Fuel and Oudtshoorn Street, Coronationville, Johannesburg, Gauteng 2093 South Africa
FUNDING SOURCES
Name of source Street address City Postal code Country
Agence Nationale de Recherche sur le Sida 101 RUE DE TOLBIAC, Paris 75013 France
South African Medical Research Council Francie Van Zijl Dr, Parow Valley, Cape Town 7501 South Africa
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor South African Medical ResearchCouncil Francie Van Zijl Dr, ParowValley CapeTown 7501 South Africa Research
COLLABORATORS
Name Street address City Postal code Country
Agence Nationale de Recherche sur le Sida 101 RUE DE TOLBIAC Paris 75013 France
CONTACT PEOPLE
Role Name Email Phone Street address
Public Enquiries Kerusha Chunderduri Kerusha.Chunderduri@mrc.ac.za +27312423638 491 Peter Mokaba Road
City Postal code Country Position/Affiliation
Durban 4091 South Africa Quality and Regulatory Coordinator
Role Name Email Phone Street address
Principal Investigator Terusha Chetty Terusha.Chetty@mrc.ac.za +27312034733 491 Peter MokabaRoad
City Postal code Country Position/Affiliation
Durban 4092 South Africa National Principal Investigator
Role Name Email Phone Street address
Principal Investigator Nobubelo Ngandu Nobubelo.Ngandu@mrc.ac.za +27219380316 Francie Van Zijl Drive
City Postal code Country Position/Affiliation
Cate Town 7505 South Africa Principal Investigator
Role Name Email Phone Street address
Scientific Enquiries Ameena Goga Ameena.Goga@mrc.ac.za +27123398524 1 Soutpansberg Road
City Postal code Country Position/Affiliation
Pretoria 0002 South Africa Coordinating Investigator
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes Individual de-identified participant data will be available, for results reported in the main and other articles. The study protocol will also be made available. The data will be available from 3 months, ending 36 months after article publication. Proposals from Scientists who provide a sound methodological proposal to the coordinating investigators will be considered for individual participant meta-analysis. Proposals may be submitted up to 36 months following article publication. A signed data access agreement will need to be signed. Informed Consent Form,Study Protocol Feb 2023- Feb 2026 Must sign a non-disclosure agreement Must agree to TOPIA terms and conditions. Must agree to use deidentified data and samples Must agree to only use data and samples as per the approved proposal/agreement by the sponsor, ethics and regulatory bodies
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