Pivotal Phase 2b/3 ALVAC/Bivalent gp120/MF59 HIV Vaccine Prevention Safety and Efficacy Study in South Africa

NCT02968849 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: HVTN 702
• Study Type: interventional
• Target: 5,404
• Locations: 1 country
• Sites: 14

Brief Summary

This study will evaluate the preventive vaccine efficacy, safety, and tolerability of ALVAC-HIV (vCP2438) + Bivalent Subtype C gp120/MF59 in HIV-seronegative South African adults over 24 months and potentially up to 36 months from enrollment.

Conditions

HIV Infections

Keywords

HIV

Outcome Measures

Primary Outcomes (12)

• Incidence Rate of HIV-1 Infection Diagnosed After Enrollment (Concurrent With First Vaccination) Through 24 Months After Enrollment

  Vaccine efficacy was calculated as 1 minus the hazard ratio for HIV-1 infection, which was estimated using a sex-stratified Cox proportional-hazards (Cox PH) model and tested using a sex-stratified log-rank test. Vaccine efficacy was also measured using a ratio of cumulative incidences (CIR) of HIV-1 infection in the vaccine group as compared with the placebo group, which was calculated using Nelson-Aalen cumulative hazard estimates and tested using a Wald test.

  Measured through 24 months after first vaccination

• Number of Participants Reporting Local Reactogenicity Signs and Symptoms: Pain and/or Tenderness

  Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 \[July 2017\]. The maximum grade observed for each symptom over the time frame is presented.

  Measured through 3 full days following each vaccination

• Number of Participants Reporting Local Reactogenicity Signs and Symptoms: Erythema and/or Induration

  Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 \[July 2017\]. The maximum grade observed for each symptom over the time frame is presented.

  Measured through 3 full days following each vaccination

• Number of Participants Reporting Systemic Reactogenicity Signs and Symptoms

  Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 \[July 2017\]. The maximum grade observed for each symptom over the time frame is presented.

  Measured through 3 full days following each vaccination

• Number of Participants Reporting Adverse Events (AEs), by Relationship to Study Product

  For participants reporting multiple AEs over the time frame, the maximum relationship is counted.

  Measured through 30 days after each vaccination

• Number of Participants Reporting Adverse Events (AEs), by Severity Grade

  For participants reporting multiple AEs over the time frame, the maximum severity grade is counted.

  Measured through 30 days after each vaccination

• Number of Participants Reporting Serious Adverse Events (SAEs)

  Measured as outlined in Version 2.0 (January 2010) of the Manual for Expedited Reporting of Adverse Events to DAIDS (DAIDS EAE Manual).

  Measured through 12 months after last vaccination

• Number of Participants Reporting Adverse Events of Special Interest (AESIs)

  Adverse events of special interest (AESI) were described in Appendix J of the protocol. AESI for this protocol include but are not limited to potential immune-mediated diseases.

  Measured through 12 months after last vaccination

• Number of Participants Reporting New Chronic Medical Conditions

  A new chronic medical condition is defined as a new onset or exacerbation of medical condition requiring 2 or more visits to a medical provider during a period of at least 30 days.

  Measured through 12 months after last vaccination

• Number of Participants With Early Study Termination Associated With an AE or Reactogenicity

  From the termination form, early study termination associated with an AE or reactogenicity reasons are tabulated by treatment group.

  Measured through study completion (through 6 months after confirmation of HIV-1 diagnosis for participants who acquired HIV and through 12 months after last vaccination for the rest)

• Number of Participants With Study Product Discontinuation Associated With an AE or Reactogenicity

  From the study product discontinuation form, study product discontinuation reasons are tabulated by treatment group.

  Measured through study completion (through 6 months after confirmation of HIV-1 diagnosis for participants who acquired HIV and through 12 months after last vaccination for the rest)

• Incidence Rate of HIV-1 Infections Diagnosed Following Enrollment and Throughout All Participant Follow-Up

  Per the 23 January 2020 DSMB finding that monitoring boundaries for non-efficacy have been met, Primary outcome 1 has been superseded by this primary outcome. Vaccine efficacy was calculated as 1 minus the hazard ratio for HIV-1 infection, which was estimated using a sex-stratified Cox proportional-hazards (Cox PH) model and tested using a sex-stratified log-rank test. Vaccine efficacy was also measured using a ratio of cumulative incidences (CIR) of HIV-1 infection in the vaccine group as compared with the placebo group, which was calculated using Nelson-Aalen cumulative hazard estimates and tested using a Wald test.

  Measured through 36 months after first vaccination

Secondary Outcomes (18)

• Incidence Rate of HIV-1 Infection Diagnosed After Enrollment Through 36 Months Post Enrollment

  Measured through 36 months after first vaccination

• Incidence Rate of HIV-1 Infection Diagnosed After Month 6.5 Through 24 Months Post Enrollment

  Measured after Month 6.5 through 24 months after first vaccination

• Number of Participants With Occurrence of CD4+ and CD8+ T-Cells Expressing IFN-g and/or IL-2 in Response to HIV Proteins Included in the Vaccine at Month 6.5

  Measured at Month 6.5

• Number of Participants With Occurrence of CD4+ and CD8+ T-Cells Expressing IFN-g and/or IL-2 and/or CD40L in Response to HIV Proteins Included in the Vaccine at Month 6.5

  Measured at Month 6.5

• Level of CD4+ and CD8+ T-Cells Expressing IFN-g and/or IL-2 in Response to HIV Proteins Included in the Vaccine at Month 6.5

  Measured at Month 6.5

Study Arms (2)

ALVAC-HIV + subtype C gp120/MF59

ACTIVE COMPARATOR

2700 participants will receive an IM injection of ALVAC-HIV (vCP2438) at months 0 and 1, and an IM injection of ALVAC-HIV (vCP2438) + Bivalent Subtype C gp120/MF59 at months 3, 6, and 12.

Biological: ALVAC-HIV (vCP2438); Biological: Bivalent Subtype C gp120/MF59

Placebo

PLACEBO COMPARATOR

2700 participants will receive Sodium Chloride for injection, 0.9% at months 0, 1, 3, 6, and 12.

Biological: Placebo

Interventions

ALVAC-HIV (vCP2438) BIOLOGICAL

Expresses the gene products ZM96 gp120 (clade C strain) linked to the sequences encoding the HIV-1 transmembrane anchor (TM) sequence of gp41 (28 amino acids clade B LAI strain) and gag and pro (clade B LAI strain). It is formulated as a lyophilized vaccine for injection at a dose \> 10\^6 cell culture infectious dose 50% (CCIDv50) and \< 1 × 10\^8 CCIDv50 (nominal dose of 10\^7 CCIDv50) and is reconstituted with 1 mL of sterile sodium chloride solution (NaCl 0.4%) delivered IM

ALVAC-HIV + subtype C gp120/MF59

Bivalent Subtype C gp120/MF59 BIOLOGICAL

Subtype C TV1.C gp120 Env and 1086.C gp120 Env proteins, each at a dose of 100 mcg, mixed with MF59 adjuvant (an oil-in-water emulsion) and delivered IM

ALVAC-HIV + subtype C gp120/MF59

Placebo BIOLOGICAL

Sodium Chloride for injection, 0.9% delivered IM

Placebo

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Age of 18 to 35 years
• Sexually active, defined as having had sexual intercourse at least twice in the past 30 days prior to screening, and is considered by the site staff to be at risk for HIV infection.
• Access to a participating HVTN 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 prior to first vaccination with verbal demonstration of understanding of all questions.
• Agrees not to enroll in another study of an investigational research agent until the participant is unblinded or their study participation ends, whichever occurs last
• Good general health as shown by medical history, physical exam, and screening laboratory tests
• Willingness to receive HIV test results
• Willingness to discuss HIV infection risks and willing to receive HIV risk reduction counseling.
• Alanine aminotransferase (ALT) \< 2.5 times the institutional upper limit of normal
• Negative HIV-1 and -2 blood test within 30 days prior to enrollment: Sites may use locally available assays that have been approved by HVTN Laboratory Operations.
• Volunteers who were born female: negative serum or urine beta human chorionic gonadotropin (β-HCG) pregnancy test performed prior to vaccination on the day of initial vaccination. Persons who are NOT of reproductive potential due to having undergone total hysterectomy or bilateral oophorectomy (verified by medical records), are not required to undergo pregnancy testing.
• Reproductive status: A volunteer who was born female must:
• Agree to consistently use effective contraception (Appendix B and Appendix C) for sexual activity that could lead to pregnancy from at least 21 days prior to enrollment through 3 months after the last vaccination. Effective contraception is defined as using 2 methods of birth control. These include 1 of the following methods:
• Condoms (male or female)

You may not qualify if:

• Blood products received within 90 days before first vaccination
• Investigational research agents received within 30 days before first vaccination
• Intent to participate in another study of an investigational research agent or any other study that requires non-HVTN HIV antibody testing during the planned duration of the study
• Pregnant or breastfeeding
• HIV vaccine(s) received in a prior HIV vaccine trial. For volunteers who have received control/placebo in an HIV vaccine trial, the HVTN 702 PSRT will determine eligibility on a case-by-case basis.
• Non-HIV experimental vaccine(s) received within the last 5 years in a prior vaccine trial. Exceptions may be made for vaccines that have subsequently undergone licensure. For volunteers who have received control/placebo in an experimental vaccine trial, the protocol safety review team will determine eligibility on a case-by-case basis. For volunteers who have received an experimental vaccine(s) greater than 5 years ago, eligibility for enrollment will be determined by the protocol safety review team on a case-by-case basis.
• Live attenuated vaccines other than influenza vaccine received within 30 days before first vaccination or scheduled within 14 days after injection (eg, measles, mumps, and rubella \[MMR\]; oral polio vaccine \[OPV\]; varicella; yellow fever)
• Influenza vaccine or any vaccines that are not live attenuated vaccines and were received within 14 days prior to first vaccination (eg, tetanus, pneumococcal, Hepatitis A or B)
• Serious adverse reactions to vaccines or to vaccine components such as eggs, egg products, or neomycin including history of anaphylaxis and related symptoms such as hives, respiratory difficulty, angioedema, and/or abdominal pain. (Not excluded from participation: a volunteer who had a non-anaphylactic adverse reaction to pertussis vaccine as a child.)
• Immunoglobulin received within 60 days before first vaccination
• Immunodeficiency
• 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,
• Any contraindication to repeated injections or blood draws,

Sponsors & Collaborators

• GlaxoSmithKline: collaborator
• Bill and Melinda Gates Foundation: collaborator
• National Institute of Allergy and Infectious Diseases (NIAID): lead
• Sanofi: collaborator

Study Sites (14)

Walter Sisulu University HIV Vaccine Research Unit CRS

Mthatha, Eastern Cape, 5099, South Africa

Location

Kliptown Soweto CRS

Johannesburg, Gauteng, 1409, South Africa

Location

Aurum Tembisa CRS

Johannesburg, Gauteng, 1632, South Africa

Location

Soweto HVTN CRS

Johannesburg, Gauteng, 1862, South Africa

Location

MeCRU CRS

Pretoria, Gauteng, 0204, South Africa

Location

Setshaba Research Centre CRS

Soshanguve, Gauteng, 0152, South Africa

Location

eThekwini CRS

Durban, KwaZulu-Natal, 4013, South Africa

Location

Isipingo CRS

Isipingo, KwaZulu-Natal, 4110, South Africa

Location

Qhakaza Mbokodo Research Clinic CRS

Ladysmith, KwaZulu-Natal, 3370, South Africa

Location

Verulam CRS

Verulam, KwaZulu-Natal, South Africa

Location

Aurum Institute Klerksdorp CRS

Klerksdorp, North West, 2571, South Africa

Location

Rustenburg CRS

Rustenburg, North West, 0300, South Africa

Location

Emavundleni CRS

Cape Town, Western Cape, 7750, South Africa

Location

Khayelitsha CRS

Cape Town, Western Cape, 7784, South Africa

Location

Related Publications (6)

• Gray GE, Bekker LG, Laher F, Malahleha M, Allen M, Moodie Z, Grunenberg N, Huang Y, Grove D, Prigmore B, Kee JJ, Benkeser D, Hural J, Innes C, Lazarus E, Meintjes G, Naicker N, Kalonji D, Nchabeleng M, Sebe M, Singh N, Kotze P, Kassim S, Dubula T, Naicker V, Brumskine W, Ncayiya CN, Ward AM, Garrett N, Kistnasami G, Gaffoor Z, Selepe P, Makhoba PB, Mathebula MP, Mda P, Adonis T, Mapetla KS, Modibedi B, Philip T, Kobane G, Bentley C, Ramirez S, Takuva S, Jones M, Sikhosana M, Atujuna M, Andrasik M, Hejazi NS, Puren A, Wiesner L, Phogat S, Diaz Granados C, Koutsoukos M, Van Der Meeren O, Barnett SW, Kanesa-Thasan N, Kublin JG, McElrath MJ, Gilbert PB, Janes H, Corey L; HVTN 702 Study Team. Vaccine Efficacy of ALVAC-HIV and Bivalent Subtype C gp120-MF59 in Adults. N Engl J Med. 2021 Mar 25;384(12):1089-1100. doi: 10.1056/NEJMoa2031499.

  PMID: 33761206 BACKGROUND

• Moodie Z, Dintwe O, Sawant S, Grove D, Huang Y, Janes H, Heptinstall J, Omar FL, Cohen K, De Rosa SC, Zhang L, Yates NL, Sarzotti-Kelsoe M, Seaton KE, Laher F, Bekker LG, Malahleha M, Innes C, Kassim S, Naicker N, Govender V, Sebe M, Singh N, Kotze P, Lazarus E, Nchabeleng M, Ward AM, Brumskine W, Dubula T, Randhawa AK, Grunenberg N, Hural J, Kee JJ, Benkeser D, Jin Y, Carpp LN, Allen M, D'Souza P, Tartaglia J, DiazGranados CA, Koutsoukos M, Gilbert PB, Kublin JG, Corey L, Andersen-Nissen E, Gray GE, Tomaras GD, McElrath MJ. Analysis of the HIV Vaccine Trials Network 702 Phase 2b-3 HIV-1 Vaccine Trial in South Africa Assessing RV144 Antibody and T-Cell Correlates of HIV-1 Acquisition Risk. J Infect Dis. 2022 Aug 24;226(2):246-257. doi: 10.1093/infdis/jiac260.

  PMID: 35758878 BACKGROUND

• Moodie Z, Li SS, Giorgi EE, Williams LD, Dintwe O, Carpp LN, Chen S, Seaton KE, Sawant SS, Zhang L, Heptinstall J, Liu S, Grunenberg N, Tomaka F, Rerks-Ngarm S, Pitisuttithum P, Nitayaphan S, Ake JA, Vasan S, Pantaleo G, Frank I, Baden LR, Goepfert PA, Keefer M, Chirenje M, Hosseinipour MC, Mngadi K, Laher F, Garrett N, Bekker LG, De Rosa S, Andersen-Nissen E, Kublin JG, Lu S, Gilbert PB, Gray GE, Corey L, McElrath MJ, Tomaras GD. A polyvalent DNA prime with matched polyvalent protein/GLA-SE boost regimen elicited the most robust and broad IgG and IgG3 V1V2 binding antibody and CD4+ T cell responses among 13 HIV vaccine trials. Emerg Microbes Infect. 2025 Dec;14(1):2485317. doi: 10.1080/22221751.2025.2485317. Epub 2025 Apr 7.

  PMID: 40190112 DERIVED

• Chihana R, Jin Kee J, Moodie Z, Huang Y, Janes H, Dadabhai S, Roxby AC, Allen M, Kassim S, Naicker V, Innes C, Naicker N, Dubula T, Grunenberg N, Malahleha M, Kublin JG, Bekker LG, Gray G, Kumwenda J, Laher F. Factors associated with reactogenicity to an investigational HIV vaccine regimen in HIV vaccine trials network 702. Vaccine. 2024 Aug 13;42(20):125991. doi: 10.1016/j.vaccine.2024.05.039. Epub 2024 May 21.

  PMID: 38772835 DERIVED

• Laher F, Malahleha M, Ramirez S, Brumskine W, Otwombe K, Moodie Z, Allen M. Data quality in an HIV vaccine efficacy clinical trial in South Africa: through natural disasters and with discipline. BMC Med Res Methodol. 2023 Jun 24;23(1):147. doi: 10.1186/s12874-023-01967-9.

  PMID: 37355583 DERIVED

• Hanass-Hancock J, Carpenter B, Reddy T, Nzuza A, Gaffoor Z, Goga A, Andrasik M. Participants' characteristics and motivations to screen for HIV vaccine and monoclonal antibody trials in KwaZulu-Natal, South Africa. Trials. 2021 Dec 11;22(1):897. doi: 10.1186/s13063-021-05792-7.

  PMID: 34895272 DERIVED

MeSH Terms

Conditions

HIV Infections

Interventions

AIDSVAX

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Results Point of Contact

• Title: Yunda Huang, PhD, Multiple Principal Investigator, HVTN Statistical and Data Management Center
• Organization: Fred Hutchinson Cancer Center

hvtn.covpn.sdmc@hvtn.org

206-667-5780

Study Officials

• Glenda Gray, MD

  Perinatal HIV Research Unit (PHRU), Chris Hani Baragwanath Hospital

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 1, 2016
• First Posted: November 21, 2016
• Study Start: October 26, 2016
• Primary Completion: November 16, 2021
• Study Completion: November 16, 2021
• Last Updated: May 4, 2026
• Results First Posted: February 8, 2023

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

ZA (14)