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.: PACTR202205715278722 Date of Approval: 27/05/2022
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title PedMAb1
Official scientific title Phase I study to determine Safety and Pharmacokinetics of subcutaneous administration of potent and broadly neutralizing anti-HIV-1 monoclonal antibodies (bNAbs), given to HIV-1 exposed uninfected (HEU) neonates and infants.
Brief summary describing the background and objectives of the trial Background: Given the challenges of maternal and child access and adherence to antiretroviral (ARV) therapy (ART) in high HIV- prevalence settings, innovative biomedical solutions, including long-acting, injectable formulations, offer a paradigm shift in the pediatric HIV/AIDS epidemic. Modified HIV-1 broadly neutralizing antibodies (bNAbs) are highly potent and long-acting, and therefore have indisputable potential for protection from HIV-1 peri- and post- natal transmission. AIM: To define the optimal dose(s), the ideal combination(s) of bNAbs and timing of subcutaneous (SC) administration to prevent breast milk transmission of HIV in high-incidence regions such as South Africa. METHODS This is a sequential and randomized, phase I, single-site, single-blind, dose-finding, trial investigating the safety and pharmacokinetic (PK) profile of incrementally higher bNAb (CAP256V2LS and VRC07-523LS) doses in breastfeeding HEU neonates also treated with the standard-of-care ARV prophylaxis. It is composed of 3 steps and has 6 arms. The first step will evaluate the safety and PK profile of the bNAbs when given alone as a single SC administration at two (VRC07) or three (CAP256) increasing doses (in mg per kg body weight), respectively, within 96 hours of birth, in breastfeeding HEU neonates treated with the standard-of-care ARV prophylaxis. Forty neonates (n=8 per arm) will be enrolled into the following arms: Arm 1:5mg/kg CAP256, Arm 2:10mg/kg CAP256, Arm 3:20mg/kg CAP256, Arm 4:20 mg/kg VRC07 and Arm 5: 30 mg/kg VRC07-523LS. Step two will evaluate the safety (AE) and the PK profile of a combination of two bNAbs (CAP256 and VRC07) administered SC within 96 hours of birth in breastfeeding HEU neonates also treated with standard-of-care ARV prophylaxis. Eight neonates will be enrolled into arm 6: 60mg of CAP256 + 90mg of VRC07.The same 8 neonates from arm 6 will roll into arm 6b: 120mg CAP256 + 120 mg VRC07 administered 3 months after the first administration.
Type of trial RCT
Acronym (If the trial has an acronym then please provide) PedMAb1
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 27/06/2022
Actual trial start date 01/09/2022
Anticipated date of last follow up 30/04/2025
Actual Last follow-up date
Anticipated target sample size (number of participants) 48
Actual target sample size (number of participants)
Recruitment status Closed to recruitment,follow-up continuing
Publication URL https://doi.org/10.1186/s12879-024-09588-3
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 CAP256V2LS 5mg/kg Once Arm 1: Eight participants will receive a single SC administration of CAP256V2LS at a dose of 5mg/kg within 96 hours after birth. Participants will be followed up at days 3, 14, 28 and at months 2, 3, 4, 5 and 6 post bNAb administration, 8
Experimental Group VRC07 523LS 20mg/kg Once Arm 4: Eight participants will receive a single SC administration of VRC07-523LS at a dose of 20mg/kg within 96 hours after birth. Participants will be followed up at days 3, 14, 28 and at months 2, 3, 4, 5 and 6 post bNAb administration, 8
Control Group None 0 0 No control group 0 Uncontrolled
Experimental Group CAP256V2LS 10mg/kg Once Arm 2: Eight participants will receive a single SC administration of CAP256V2LS at a dose of 10mg/kg within 96 hours after birth. Participants will be followed up at days 3, 14, 28 and at months 2, 3, 4, 5 and 6 post bNAb administration, 8
Experimental Group CAP256V2LS 20mg/kg Once Arm 3: Eight participants will receive a single SC administration of CAP256V2LS at a dose of 20mg/kg within 96 hours after birth. Participants will be followed up at days 3, 14, 28 and at months 2, 3, 4, 5 and 6 post bNAb administration, 8
Experimental Group VRC07 523LS 30mg/kg Once Arm 5: Eight participants will receive a single SC administration of VRC07-523LS at a dose of 30mg/kg within 96 hours after birth. Participants will be followed up at days 3, 14, 28 and at months 2, 3, 4, 5 and 6 post bNAb administration, 8
Experimental Group CAP256V2LS and VRC07523LS 60mg and 90mg Once Arm 6: Eight participants will receive a first SC administration of CAP256V2LS (60mg) and VRC07-523LS (90mg) within 96h after birth. The two bNAbs will be administered in sequential order at two independent injection sites. Participants will be followed up at days 1, 3, 14, 28, 56 post bNAb administration. 8
Experimental Group CAP256V2LS and VRC07523LS 120mg and 120mg Once Arm 6b: The same eight participants from arm 6 will receive a second SC administration of CAP256V2LS (120mg) and VRC07-523LS (120mg) at 12 weeks. The two bNAbs will be administered in sequential order at two independent injection sites. Participants will be followed up at days 1, 3, 14 and 28 post 2nd bNAb administration (month 3, week 12) and at months 4, 5, 6, 7 and 8 post-delivery. 8
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
Mother • Greater than or equal to 18 years of age • Documented HIV-1 infection • Breastfeeding at the time of consenting or willing to initiate breastfeeding in the immediate post partum period. • Able and willing to provide a signed informed consent form to participate in the study for herself and her infant. Newborn • Alive infant with a birth weight greater than or equal to 2.0 kg and lower than or equal to 4.0kg • Gestational age greater or equal to 36 weeks, assessed using birth Ballard Score (done up to 42 hours after birth) • Written consent of the one or both parents (according to South African regulation) Mother • Prior participation in any HIV-1 vaccine trial • Receipt of any other active or passive HIV immunotherapy or investigational product concurrently • Documented or suspected serious medical illness with fetal compromise or immediate life-threatening condition (other than HIV-infection as judged by the examining clinician) • Most recent CD4 count (within a time frame of ≤6 months) under 350 cells/mm3 • Mother not on ART • Unable or not willing to breastfeed • Active tuberculosis • COVID-19 diagnosis in the past month • Plan to relocate in 1 year • Mother does not have her own cell phone • Mother not able to provide two alternate contact phone numbers Newborn • HIV-infected on birth PCR • Receipt of or anticipated need for blood product, immunoglobulin or immunosuppressive therapy. This includes infants who require hepatitis B immunoglobulins (HBIG) but not infants who receive hepatitis B vaccine in the new-born period • Documented or suspected serious medical or immediate life-threatening condition • Infant in ICU or high care requiring supplemental oxygen at time of first bNAb dose • Known allergy to study drug or components • Multiple birth, i.e. twins, triplets, quadruplets, etc • Baseline laboratory results: • Haemoglobin level less than 12.0 g/dL • Platelet count less than 100,000 cells/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 than 1,250 cells/mm3 • Serum glutamic pyruvic transaminase (SGPT), alanine aminotransferase (ALT) greater than or equal to 1.25 times upper limit of age-adjusted normal. • Serum bilirubin at a level needing phototherapy Adult: 19 Year-44 Year,Infant: 0 Month(s)-12 Month(s),New born: 0 Day-1 Month 0 Day(s) 44 Year(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 13/12/2021 SAMRC HREC
Ethics Committee Address
Street address City Postal code Country
Francie Van Zijl Drive 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 13/06/2022 SAMRC HREC
Ethics Committee Address
Street address City Postal code Country
Francie Van Zijl Drive 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 07/06/2022 SAHPRA
Ethics Committee Address
Street address City Postal code Country
Kirkness Road Acrcadia Pretoria 0001 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 02/02/2023 SAMRC HREC
Ethics Committee Address
Street address City Postal code Country
Francie Van Zijl Drive 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 23/04/2024 SAMRC HREC
Ethics Committee Address
Street address City Postal code Country
Francie Van Zijl Drive Cape Town 7505 South Africa
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome To evaluate the safety (adverse events) until day 28 after a single SC administration of one bNAb, tested at increasing doses within 96 hours of birth, in breastfeeding HEU neonates (arms 1 through 5). 28 days after first bNAb administration within 96 hours of birth
Primary Outcome To evaluate the safety (adverse events) until day 28 after two single SC administration of two bNAbs, tested at increasing doses within 96 hours of birth, in breastfeeding HEU neonates (arm 6). 28 days after first bNAb administration within 96 hours of birth
Primary Outcome To evaluate the safety (adverse events) until day 28 after two single SC administrations of two bNAbs, within 96 hours of birth and repeated at 3 months (arms 6b) in breastfeeding HEU neonates 28 days after each bNAb administration
Secondary Outcome To evaluate the PK profile up to 6 months of each single bNAb administered, alone or in combination, at different doses within 96 hours of birth in breastfeeding HEU neonates (arms 1 through 5). 6 months
Secondary Outcome To evaluate the PK profile up to 3 months of bNAbs administered in combination, at different doses within 96 hours of birth in breastfeeding HEU (arm 6). 3 months
Secondary Outcome To evaluate the PK profile up to 6 months of each bNAb, administered in combination, in breastfeeding HEU infants after a second administration at 3 months (arms 6/6b). 9 months
Secondary Outcome To assess safety (adverse events) up to 6 months after each single bNAb (arms 1 to 5) or up to 3 months after the first combined bNAb administration (arms 6) or up to 6 months after the second combined bNAb administration arm 6b 6 months
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
South Africa Medical Research Council SAMRC Chatsworth Clinical Research site RK Khan Circle Durban 4030 South Africa
FUNDING SOURCES
Name of source Street address City Postal code Country
European and Developing Countries Clinical Trials Partnership Anna van Saksenlaan 51 The Hague 2593 Netherlands
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor South African Medical Research Council Francie Van Zijl Drive Cape Town 7505 South Africa Commercial Sector/Industry
COLLABORATORS
Name Street address City Postal code Country
Gabriella Scarlatti Via Olgettina 60 Milan 20132 Italy
Philippe Van de Perre INSERM UMR 1058 Montpellier France
Thorkild Tylleskar 5007 Bergen Bergen Norway
Penny Moore 31 Princess of Wales Terrace, Parktown Johannesburg South Africa
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Logashvari Naidoo logashvari.naidoo@mrc.ac.za +27312423688 491 Peter Mokaba Ridge, Overport
City Postal code Country Position/Affiliation
Durban 4067 South Africa Principal Investigator
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 Regulatory and Quality Coordinator
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 Unit Director
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes Will individual participant data be available (including data dictionaries)? Yes What data in particular will be shared? All of the individual participant data collected during the trial, will only be shared after deidentification What other documents will be available? None When will data be available (start and end date)? Anticipated start date 27th June 2022 Anticipated end date December 2025 With who? Anyone wishing to access the data during the study or after should write to the co-investigators (CIs) with an outline of the analysis they would like to undertake. The CIs will then decide whether to grant access to the data to this researcher and inform the researcher within one month of the application receipt. Note: All shared data will be de-identified. Research teams who would like to use data obtained during the research and/or to use stored samples should write a proposal and send it to the coordinating and principal investigators, They should also ensure they receive Ethics approval for their analyses. Note: All shared data will be deidentified. For what types of analyses? To achieve aims in the approved proposal By what mechanism will date be made available The CIs assume overall ownership of the database and will regulate access. A data users’ agreement and data request form will need to be completed and submitted to the CIs. All requests for data access will be reviewed and subject to the approval of the CIs and study investigators. The User needs to agree to use appropriate safeguards for data protection and shall notify the CIs of any unauthorised data use or disclosure of which they become aware. Note: All shared data will be de-identified. Study Protocol 6 months to 2 years from study completion. to be confirmed with study sponsor Data will be shared among the Study Investigators and the study statisticians, after cleaning has been completed, in order to proceed with the analyses and results dissemination.
URL Results Available Results Summary Result Posting Date First Journal Publication Date
https://pedmab.w.uib.no/ and https://pedmab.samrc.ac.za/ 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