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.: PACTR202309578224660 Date of Approval: 22/09/2023
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title CAPRISA 095 Study: Phase 1 study to assess the effect of broadly neutralizing monoclonal antibodiesCAP256V2LS and VRC07-523LS combined with antiretroviral therapy on the HIV-1 latent reservoir (NeutART)
Official scientific title Phase 1 study to evaluate if broadly neutralizing monoclonal antibodies CAP256V2LS and VRC07-523LS, combined with antiretroviral therapy (ART), will result in sustained virological control following analytical treatment interruption.
Brief summary describing the background and objectives of the trial The advent of antiretroviral therapy (ART) has both slowed the transmission of HIV-1 and prolonged the lives of those infected. However, HIV-1 remains incurable due to a latent viral reservoir that exists during suppressive therapy. In addition, the virus rebounds upon therapy interruption. The best-characterized reservoir is the circulating resting, memory CD4+ T cells where replication competent virus is found in a very low frequency of cells at ~1-10 per million CD4+ cells. HIV-1 can persist in other anatomical sites including lymph nodes in B cell follicles, the genital tract, the brain, and gut. Prior to treatment, the virus is rapidly eliminated (half-life of days),with a population of virus-infected cells where the turn-over is slower (half-life of weeks). Long-lived CD4+Tcells containing integrated latent virus occur at much lower frequency than these first two components and have a half-life of approximately four years. The major obstacle in curing HIV is the viral reservoir. We propose that reduction in the size of the reservoir using a combination of monoclonal antibodies and ART will lower the barrier to eradicating HIV-1 from an infected person. We propose that this regime will reduce the reservoir size by (i) clearing circulating virus and preventing infection of transitioning CD4 T-cells; (ii) antibody-mediated killing of virus infected cells; and (iii) lastly by enhancing of autologous antibody responses. Primary objective : 1. To determine whether monoclonal antibodies CAP256V2LS and VRC07-523LS, combined with ART affects time to viral load rebound and time to ART re-initiation post ATI 2. To assess the safety of CAP256V2LS and VRC07-523LS administered IV to HIV positive participants in combination with ART. Secondary objectives: 1. To understand whether, and how CAP256V2LS and VRC07-523LS, combined with ART, affects the formation and size of the HIV-1 latent reservoir
Type of trial RCT
Acronym (If the trial has an acronym then please provide) NeutART
Disease(s) or condition(s) being studied Infections and Infestations
Sub-Disease(s) or condition(s) being studied HIV/AIDS
Purpose of the trial Treatment: Drugs
Anticipated trial start date 23/10/2023
Actual trial start date
Anticipated date of last follow up 27/10/2025
Actual Last follow-up date
Anticipated target sample size (number of participants) 30
Actual target sample size (number of participants)
Recruitment status Not yet recruiting
Publication URL
Secondary Ids Issuing authority/Trial register
20220612 SAHPRA
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 Open-label(Masking Not Used)
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group Monoclonal Antibodies CAP256V2LS andVRC07-523LS :20mg/kg IV and40mg/kg IV one dose followed by ART one week later One dose at enrolment CAP256V2LS(VRCHIVMAB0102-00-AB) is a sterile aqueous buffered solution filled into 10 mL single-dose vials. Each vial contains6.25 ± 0.1 mL at a concentration of 100 ± 10mg/mL in formulation buffer. The formulation buffer is composed of 20mM Sodium Phosphate,100 mM Sodium Chloride, 75 mM L-Arginine HCl, 3% (w/w) Sucrose, and 0.01% (w/v) Polysorbate 80 at pH 7.0.VRC07-523LS is an aqueous buffered solution filled into 10 ml single-dose glass vials. Each vial contains a volume of 6.25 ± 0.1 ml or 2.25 ± 0.1 ml at a concentration of 100 ± 10mg/ml in a formulation buffer. The buffer is composed of 50 mM histidine, 50 mM sodium chloride, 5% sucrose and2.5% sorbitol, at a pH of6.8. Vials contain a sterile solution which is a clear, colourless to yellow liquid, essentially free of visible particles; some opaque or translucent particles may be present. Vials are intended for single use only and thus do not contain a preservative. 10
Experimental Group Monoclonal Antibodies CAP256V2LS andVRC07-523LS and ART : 20mg/kg IVand 40 mg/kg IV one dose; ART at same time One dose at enrolment CAP256V2LS The study product, CAP256V2LS(VRC-HIVMAB0102-00-AB) is a sterile aqueous buffered solution filled into 10 mL single-dose vials. Each vial contains6.25 ± 0.1 mL at a concentration of 100 ± 10mg/mL in formulation buffer. The formulation buffer is composed of 20mM Sodium Phosphate,100 mM Sodium Chloride, 75 mM L-Arginine HCl, 3% (w/w) Sucrose, and 0.01% (w/v) Polysorbate 80 at pH 7.0.VRC07-523LS is an aqueous buffered solution filled into 10 ml single-dose glass vials. Each vial contains a volume of 6.25 ± 0.1 ml or 2.25 ± 0.1 ml at a concentration of 100 ± 10mg/ml in a formulation buffer. The buffer is composed of 50 mM histidine, 50 mM sodium chloride, 5% sucrose and2.5% sorbitol, at a pH of6.8. Vials contain a sterile solution which is a clear, colourless to yellow liquid, essentially free of visible particles; some opaque or translucent particles may be present. Vials are intended for single use only and thus do not contain a preservative. 10
Control Group ART One dose at enrolment ART re-initiation at week 18 One dose at enrolment ART re-initiation at week 18 To determine whether monoclonal antibodiesCAP256V2LS andVRC07- 523LS, combined with ART affects the time to viral load rebound and time to ART re-initiation post ATI and to assess the safety of CAP256V2LS andVRC07-523LSadministered IV to HIV positive participants before or at the time of ART start. 10 Active-Treatment of Control Group
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
• Adults ≥18 years of age • Able and willing to complete the informed consent process CAPRISA 095 Protocol Page 15 of 33 Version 1.0 06 May 2022 • HIV-positive, ART-naïve at screening with a VL > 1000, and due to initiate ART • CD4 count of ≥ 400 cells/μl • Able and willing to participate in an ATI trial with a maximum interruption of 24 weeks after 12 months on ART • Able to understand the information provided, including the potential impact and/or risks linked to study product administration, willing to comply with protocol procedures, and has access to the clinical research site for the study duration. • Based on clinical assessment, participant must be in good general health with no major comorbidities or AIDS-defining illness, as per opinion of the Principal Investigator (PI) or designee. • Haemoglobin ≥ 10 g/dl. • Platelets ≥ 100,000 cells/mm3 • eGFR > 60 mL/min/1.73m2 • Alanine aminotransferase (ALT) < 2.5 times the institutional upper limit of normal. • Negative pregnancy test for females. • If female and of reproductive potential, has evidence of effective contraceptive use and is willing to adhere to effective contraceptive use during the study period. • Willing to have blood samples collected, stored, and used for research purposes. • Any clinically significant acute or chronic medical condition or other circumstance that in the opinion of the PI/designee makes the participant unsuitable for participation in the study or jeopardises the safety or rights of the participant. • Positive Hepatitis B surface antigen (HBsAg) or positive HCV RNA (not exclusionary: positive HCV Ab with negative HCV RNA) • For female participants, currently pregnant or breastfeeding, or planning a pregnancy during the study period. • 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 or HIV mAb 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, or angioedema. • Evidence of autoimmune disease or currently receiving immunosuppressive therapy. • Receipt of any vaccines within 14 days of enrolment. • Participants in the 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/designee. Adult: 19 Year-44 Year 18 Year(s) 30 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 26/06/2022 SAHPRA
Ethics Committee Address
Street address City Postal code Country
South African Health Products Regulatory Authority Loftus Park Building A 402 Kirkness Street Arcadia, Pretoria Pretoria 0083 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 04/04/2023 Biomedical Research Ethics Committee
Ethics Committee Address
Street address City Postal code Country
UKZN Research Ethics Office Westville Campus, Govan Mbeki Building Durban 4001 South Africa
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome To determine whether monoclonal antibodiesCAP256V2LS and VRC07-523LS, combined with ART affects time to viral load rebound / ART reinitiation post treatment interruption formation of the HIV-1 latent reservoir Change in composition and size of the reservoir at 12 months post infection as determined by the number of viruses circulating at enrolment that enter the reservoir.
Secondary Outcome To understand the mechanism of how CAP256V2LSand VRC07-523LS, combined with ART, affects the formation and size of the HIV-1 latent reservoir. Enrolment and 12 months
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
CAPRISA eThekwini Clinical Research Site 3 Richards Road Durban 4001 South Africa
CAPRISA Vulindlela Clinical Research Site Mafakatini Howick 3290 South Africa
FUNDING SOURCES
Name of source Street address City Postal code Country
South African Medical Research Council Francie van Zijl Drive Cape Town 7505 South Africa
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 719 Umbilo Road Durban 4091 South Africa Not-for-profit NGO
COLLABORATORS
Name Street address City Postal code Country
John Mascola 5601 Fisher Lane, MSC 9806 Bethesda 20892-980 United States of America
Lynn Morris 1 Modderfontein Road Johannesburg 2192 South Africa
Edmund Capparelli 9500 Gilman Drive, La Jolla San Diego 92093 United States of America
Salim S. Abdool Karim 719 Umbilo Road Durban 4013 South Africa
Ron Swanstrom 103 S Bldg Cb 9100 Chapel Hill 27599 United States of America
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Nigel Garrett Nigel.Garrett@caprisa.org +27316550617 3 Richards Road, Berea
City Postal code Country Position/Affiliation
Durban 4001 South Africa Head of Pathogenesis and Vaccine Research
Role Name Email Phone Street address
Scientific Enquiries Sharana Mahomed Sharana.Mahomed@caprisa.org +27312605610 3 Richards Road, Berea
City Postal code Country Position/Affiliation
Durban 4001 South Africa Site Principal Investigator
Role Name Email Phone Street address
Public Enquiries Nirosha Gokul Nirosha.Gokul@caprisa.org +27316550649 3 Richards Road, Berea
City Postal code Country Position/Affiliation
Durban 4001 South Africa Study Coordinator
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes The sponsor will register and disclose the results of clinical studies as required by law. The disclosure of the final study results will be performed after the end of study in order to ensure the statistical analyses are relevant. Informed Consent Form,Study Protocol Within 12 months of the study completion date The results of the study will be reported in a Clinical Study Report generated by the sponsor and will contain data from all study sites that participated in the study as PP. Recruitment performance or specific expertise related to the nature and the key assessment parameters of the study will be used to determine a coordinating investigator for the study. Results of analyses performed after the Clinical Study Report has been issued will be reported in a separate report and will not require a revision of the Clinical Study Report. Study participant identifiers will not be used in publication of results. Any work created in connection with performance of the study and contained in the data that can benefit from copyright protection (except any publication by the investigator as provided for below) shall be the property of the sponsor as author and owner of copyright in such work. Consistent with Good Publication Practices and International Committee of Medical Journal Editors(ICMJE) guidelines, the sponsor shall have the right to publish such primary(multicenter) data and information without approval from the investigator.
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