HIV/AIDS
Conditions
Interventions
Sponsors
South African Medical Research Council
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: General and Demographic Criteria ? Age of 18 up to 40 years. ? Access to a participating CRS and willingness to be followed for the planned duration of the study. ? Ability and willingness to provide informed consent. ? Assessment of understanding: volunteer demonstrates understanding of this study and completes a questionnaire prior to first vaccination with verbal demonstration of understanding of all questionnaire items answered incorrectly. ? Willing to be contacted annually after completion of scheduled clinic visits for a total of 2 years following initial study injection. ? Agrees not to enrol in another study of an investigational product during participation in the trial. ? Agrees not to enrol into any other study (whether interventional or non–interventional), without informing the site principal investigator. Prior PSRT approval is required for any co-enrolment decisions. ? Good general health according to the clinical judgement of the site investigator. ? HIV-Related Criteria: o Willingness to receive HIV test results. o Willingness to discuss HIV infection risks and amenable to HIV risk reduction counselling. o Assessed by the clinic staff as being at “low risk” for HIV infection and committed to maintaining Behavior consistent with low risk of HIV exposure through the last required protocol clinic visit. Laboratory Inclusion Values 1. Full blood count (FBC): ? Haemoglobin o = 11.0 g/dL for volunteers who were assigned female sex at birth o = 13.0 g/dL for volunteers who were assigned male sex at birth ? White blood cell count = 2,500 cells/mm3 with normal differential, or differential approved by Clinical trial site Principal Investigator (PI) as not clinically significant ? Total lymphocyte count = 650 cells/mm3 with normal differential, or differential approved by the Principal Investigators as not clinically significant ? Remaining differential either within institutional normal range or with investigator approval. ? Platelets = 125,000 cells/mm3. 2. Chemistry: ? Alanine aminotransferase (ALT) 8.5 mg/dL Virology ? Negative HIV-1 and HIV-2 blood test. ? Negative Hepatitis B surface antigen (HBsAg). ? Negative anti-Hepatitis C virus antibodies (anti-HCV) ? Normal urinalysis: Urine protein or haemoglobin negative If protein or blood/haemoglobin on urine dipstick, see Section 9.11. Reproductive Status ? Volunteers who were assigned female sex at birth: negative serum or urine beta human chorionic gonadotropin (ß-HCG) pregnancy test at screening (i.e., prior to randomization) and prior to study product administration on the day of study product administration. Persons who are NOT of reproductive potential due to having undergone hysterectomy or bilateral oophorectomy (verified by medical records), are not required to undergo pregnancy testing. ? Reproductive status: A volunteer who was assigned female sex at birth: Must agree to use effective contraception for sexual activity that could lead to pregnancy from at least 21 days prior to enrolment through to Visit 11. Effective contraception is defined as using the following methods: Intrauterine device (IUD), Hormonal contraception, Tubal ligation, or Any other contraceptive method approved by the PSRT Or not be of reproductive potential, such as having reached menopaus
Exclusion criteria
Exclusion criteria: General 1. Blood products received within 120 days before first vaccination. 2. Has donated =450 mL of blood products within 28 days prior to the enrolment visit or plans to donate blood products during or within 28 days post-study participation. 3. Investigational products received within 30 days before first vaccination. 4. Body mass index (BMI) =18 and = 40 5. Previous or current recipient of an investigational product or any other study that requires HIV antibody testing during the planned duration of the study. 6. Pregnant or breastfeeding 7. Is working or has worked as study personnel or is an immediate family member or house member of study personnel, study site staff, or sponsor personnel Vaccines and other Injections 1. HIV vaccine(s) received in a prior HIV vaccine trial. For volunteers who have received control/placebo in an HIV vaccine trial, the PSRT will determine eligibility on a case-by-case basis. 2. Previous receipt of monoclonal antibodies (mAbs), whether licensed or investigational. Exceptions may be made by the PSRT on a case-by-case basis. 3. Non-HIV experimental vaccine(s) received within the last 1 year in a prior vaccine trial. 4. Live attenuated vaccines received within 30 days before first vaccination or scheduled within 28 days after injection (e.g., measles, mumps, and rubella [MMR]; oral polio vaccine [OPV]; varicella; yellow fever; live attenuated influenza vaccine). 5. Any vaccines that are not live attenuated vaccines and were received within 14 days prior to first vaccination (e.g., tetanus, pneumococcal, Hepatitis A or B). 6. Allergy treatment with antigen injections within 30 days before first vaccination or that are scheduled within 14 days after first vaccination. Immune System 1. Immunosuppressive medications received within 6 months before first vaccination (Not exclusionary: [1] corticosteroid nasal spray; or [2] a single course of oral/parenteral prednisone or equivalent at doses < 60 mg/day and length of therapy < 11 days with completion at least 30 days prior to enrolment) for an acute, non-recurrent condition. 2. Serious adverse reactions to vaccines including history of anaphylaxis and related symptoms such as hives, respiratory difficulty, angioedema, and/or abdominal pain. 3. Immunoglobulin received within 90 days before first vaccination (for mAbs see criterion 2 in “Vaccines and other Injections” above). 4. Autoimmune disease, current or history 5. AESIs: A participant with a history of a potential immune-mediated medical condition (PIMMC), either ongoing or resolved. Specific examples are listed in Appendix H. 6. History of anaphylaxis, and any allergies that have ever required corticosteroids or visits to the emergency department. 7. Hereditary angioedema, acquired angioedema, or idiopathic forms of angioedema 8. Immunodeficiency: Congenital or acquired immunodeficiency, including systemic medication use likely to impair immune response to vaccine in the opinion of the site investigator Clinically significant medical conditions 1. Clinically significant medical condition, physical examination findings, clinically significant abnormal laboratory results, or past medical history with clinically significant implications for current health. A clinically significant condition or process includes but is not limited to: ? A process that would affect the immune response, ? A process that would require medication that affects the immune response, ? An
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To determine the safety and tolerability of 426c.Mod.Core-C4b and BG505 GT1.1 immunogens in prime-boost combinations with 3M-052-AF and Alum adjuvants in HIV negative adults. •To determine the quality and quantity of Env-specific binding antibodies (Abs) elicited by vaccination with 426c.Mod.Core-C4b and BG505 GT1.1 immunogens in prime-boost or cocktail combinations with 3M-052-AF and Alum adjuvants. •To evaluate and compare the neutralizing antibody (nAb) responses determine neutralizing properties of vaccine-induced Abs after immunization with 426c.Mod.Core-C4b and BG505 GT1.1 in different prime-boost combinations. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary Objective 1: To evaluate and compare immune responses elicited by 426c.Mod.Core-C4b and BG505 GT1.1 immunogens in prime-boost combinations and as a cocktail. Secondary endpoint 1: Response rate and magnitude of lgG+ CD4 binding site (CD4-bs) B cells as measured by BG505 GT1.1 and 426c.Mod.Core-C4b tetramer binding by multiparameter flow cytometry. Secondary endpoint 2: Genetic changes associated with the development of bnAbs represented as the frequency of VRC01-like BCR sequences determined by VHNL sequencing of sorted B cells, including germline gene usage and somatic hypermutation. Secondary endpoint 3: Response rate and magnitude of HIV Env-specific CD4+ T cells as measured by multiparameter flow cytometry. | — |
Countries
South Africa
Contacts
Public ContactKubashni Woeber
Program Manager
Outcome results
None listed