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: www.pactr.org
Trial no.: PACTR201808919297244 Date of Approval: 29/08/2018
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title CAPRISA 012A
Official scientific title A Phase ǀ Study to determine the Safety and Pharmacokinetics of the Human monoclonal Antibodies, VRC07-523LS and PGT121 administered subcutaneously to HIV negative Adults in South Africa
Brief summary describing the background and objectives of the trial The overall goal of the CAPRISA 012 trial is to develop a combination of two anti-HIV mAbs as a new, safe and effective long-acting HIV prevention technology, principally for women. The trial aims to fast-track and efficiently advance passive immunization as an emerging HIV prevention strategy. The CAPRISA 012 trial will be conducted in two parts. The aim of Part A CAPRISA 012A (described in this summary) is to determine the safety and pharmacokinetic (PK) profile of the human mAbs VRC07-523LS and PGT121 administered subcutaneously alone and in combination to HIV negative women in South Africa Component 1 of Part B is a phase I assessment of the safety and PK of CAP256-VRC26.25LS. Based on the phase I data, one or both of the proposed two-antibody combinations will proceed to component 2 of Part B, which is a phase II trial that will assess extended safety and obtain an estimate of efficacy in preventing HIV infection in young women. Part B of the CAPRISA 012 trial will only commence following regulatory approvals. Primary objective • To evaluate the safety of one and two doses of VRC07-523LS and/or PGT121 553 mAbs administered SC. Secondary objectives • To characterize the PK profile of VRC07-523LS mAb administered SC individually as a single dose or as two doses 12 and 24 weeks apart. • To characterize the PK profile of PGT121 mAb administered SC individually as a single dose or as two doses 12 weeks apart. • To characterize the PK profile of VRC07-523LS and PGT121 mAbs administered simultaneously. • To assess the acceptability of VRC07-523LS and PGT121 mAbs SC • To evaluate the concentrations and functional activity of VRC07-523LS and/ or PGT121 mAb in plasma and genital samples following SC administration. • To determine whether SC administration of VRC07-523LS and/or PGT121 mAbs induces anti-mAbs.
Type of trial RCT
Acronym (If the trial has an acronym then please provide) CAP 012A
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 01/10/2018
Actual trial start date 14/10/2019
Anticipated date of last follow up 31/10/2019
Actual Last follow-up date
Anticipated target sample size (number of participants) 45
Actual target sample size (number of participants)
Recruitment status Completed
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 Sealed opaque envelopes Masking/blinding used Care giver/Provider,Outcome Assessors,Participants
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group Group 2 10mg/kg SC one dose VRC07-523LS 4
Experimental Group Group 3 5 mg/kg SC one dose with one repeat dose at 12 weeks VRC07-523LS 4
Experimental Group Group 1 5 mg/kg SC one dose VRC07-523LS 4
Experimental Group Group 4 10 mg/kg SC one dose with one repeat dose at 24 weeks VRC07-523LS 4
Experimental Group Group 5 3mg/kg SC one dose PGT121 4
Experimental Group Group 6 3mg/kg SC one dose with one repeat dose at 12 weeks PGT121 4
Experimental Group Group 7 VRC07-523LS (5mg/kg SC) + PGT121 (3mg/kg SC) one dose VRC07-523LS + PGT121 4
Control Group Control Group The dose of the placebo will match the respective experimental arm The duration of the placebo will match the respective experimental arm Placebo 7 Placebo
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
• 18 to 40 years of age • Female sex at birth • Able and willing to complete the informed consent process • Has understood the information provided, including the potential impact and/or risks linked to SC administration of the study product, and is willing to comply with protocol procedures, has accessibility to the clinical research site and is available for follow-up for the study duration • Based on clinical assessment must be in good general health as per opinion of the Principal Investigator (PI) or designee • Assessed by site staff to be at low risk for HIV • If of reproductive potential, has evidence of effective contraceptive use in the previous 21 days, and agrees to continued use during the study period • Willing to have blood and genital samples collected, stored, and used for research purposes • clinically significant acute or chronic medical condition that in the opinion of PI or designee makes the participant unsuitable for participation in the study, or jeopardizes the safety or rights of the volunteer • If planning a pregnancy for the duration of the study, currently pregnant or breastfeeding • Exceeding the weight of 90 kilograms • A history of alcohol or substance use judged by the PI to potentially interfere with participant study compliance • Prior participation in an investigational HIV vaccine trial, except if proof of allocation to the placebo arm is available • Administration of a mAb or polyclonal immunoglobulin within 28 days prior to enrolment • Any history of anaphylaxis and related symptoms such as hives, respiratory difficulty and angioedema • Evidence of autoimmune disease, or receiving immunosuppressive therapy • Participants in this study may not take part in other concurrent research studies that would interfere with the objectives of this study. The determination of whether participation in another study would be exclusionary for a given participant will be made by the PI or designee. Adult: 19 Year-44 Year 18 Year(s) 40 Year(s) Female
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 16/08/2018 Biomedical Research Ethics Committee UKZN
Ethics Committee Address
Street address City Postal code Country
University of Kwa-zulu Natal, Westville Campus, Govan Mbeki Building Durban 4000 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 11/07/2018 South African Health Products Regulatory Authority
Ethics Committee Address
Street address City Postal code Country
42 Thabo Sehume Street , Civitas Building Pretoria 0001 South Africa
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Proportion of participants with mild, moderate and severe reactogenicity events within the first 3 days after SC administration.  Proportion of participants with mild, moderate and severe adverse events up to 24 weeks after the last SC administration. As above
Secondary Outcome Maximal concentration, time of maximal concentration, area under the concentration vs time curve and terminal half-life of VRC07-523LS and PGT121 mAbs.  Proportion of participants who report that the SC injections are acceptable.  Changes in humoral immune function (neutralizing and non-neutralizing antibody function) in the systemic and genital tract compartments before and after SC mAb administration.  Changes in the concentration of serum anti- mAbs before and after SC mAb administration. as per Schedule of Evaluation
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
CAPRISA eThekwini Clinical Research Site 3 University Avenue Durban 4000 South Africa
FUNDING SOURCES
Name of source Street address City Postal code Country
The South African Medical Research Council Francie Van Zijl drive, Parowvallei Cape Town 7505 South Africa
European 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 Centre for the AIDS Programme of Research in South Africa Nelson R Mandela School of Medicine, University of KwaZulu-Natal Durban 4013 South Africa Individual
COLLABORATORS
Name Street address City Postal code Country
Vaccine Research Council 9000 Centre drive, Bethesda 20892 United States of America
Centre for Virology and Vaccine Research 330 Brookline Avenue Boston 02215 United States of America
National Institute of Communicable Diseases 1 Modderfontein road, Sandringham Johannesburg 2131 South Africa
Amsterdam Institute for Global Health and Development Tower C4, Paasheuvelweg 25 Amsterdam 1105 Netherlands
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Salim Karim Salim.AbdoolKarim@caprisa.org +27312604555 Nelson R Mandela School of Medicine, University of KwaZulu-Natal
City Postal code Country Position/Affiliation
Durban 4013 South Africa Director
Role Name Email Phone Street address
Public Enquiries Sharana Mahomed sharana.mahomed@caprisa.org +27312604555 Nelson R Mandela School of Medicine, University of KwaZulu-Natal
City Postal code Country Position/Affiliation
Durban 4013 South Africa Project Director
Role Name Email Phone Street address
Scientific Enquiries Sharana Mahomed sharana.mahomed@caprisa.org +27312604555 Nelson R Mandela School of Medicine, University of KwaZulu-Natal
City Postal code Country Position/Affiliation
Durban 4013 South Africa Project Director
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
No
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
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Actual trial start date 13/01/2020 Screening commenced after the site initiation visit 14 Oct 2019
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Target no of participants 13/01/2020 An amendment to the existing protocol was approved by regulatory authorities to include an additional 10 participants 35 45
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Recruitment status 13/01/2020 Recruitment has commenced. Active, not recruiting Recruiting
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Recruitment status 11/03/2020 All participants have been enrolled Recruiting Closed to recruitment,follow-up continuing
Section Name Field Name Date Reason Old Value Updated Value
Funding Source FundingSources List 11/03/2020 updated European Developing Countries Clinical Trials Partnership, Anna van Saksenlaan 51 , the Hague, 2593, Netherlands, Funding Agency,
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Recruitment status 21/10/2020 All participants have exited the study, data clean up in progress Closed to recruitment,follow-up continuing Completed