A Study to Assess the Efficacy of a Heterologous Prime/Boost Vaccine Regimen of Ad26.Mos4.HIV and Aluminum Phosphate-Adjuvanted Clade C gp140 in Preventing Human Immunodeficiency Virus (HIV) -1 Infection in Women in Sub-Saharan Africa

NCT03060629 | Terminated Phase 2 Results DMC FDA Drug

• 4 other identifiers: CR108263VAC89220HPX2008HVTN 705HVTN 705/VAC89220HPX2008
• Study Type: interventional
• Target: 2,636
• Locations: 4 countries
• Sites: 7

Brief Summary

The primary purpose of this study is to assess the preventive vaccine efficacy (VE), safety and tolerability of a heterologous prime/boost regimen utilizing Ad26.Mos4.HIV and aluminum-phosphate adjuvanted Clade C gp 140 for the prevention of Human Immuno Virus (HIV) infection in HIV-seronegative women residing in sub-Saharan Africa from confirmed HIV-1 infections diagnosed between the Month 7 and Month 24 visits.

Conditions

HIV-1

Outcome Measures

Primary Outcomes (16)

• Number of Participants With Human Immuno Deficiency Virus-1 (HIV-1) Infection Diagnosed Between Month 7 to Month 24 Post Enrollment

  Number of participants with HIV-1 infection diagnosed between Month 7 to Month 24 post enrollment was reported. The data represents the cumulative incidence of HIV-1 infections.

  Month 7 up to Month 24

• Percentage of Participants With Local Reactogenicity Signs and Symptoms After First Vaccination

  Percentage of participants with local reactogenicity signs and symptoms after first vaccination were reported. Local reactogenicity events (solicited local adverse events) were defined as events at the injection site. Local reactogenicity signs and symptoms included pain and/or tenderness proximal to the injection site.

  Up to 7 days after first vaccination on Day 0 (Day 7)

• Percentage of Participants With Local Reactogenicity Signs and Symptoms After Second Vaccination

  Percentage of participants with local reactogenicity signs and symptoms after second vaccination was reported. Local reactogenicity events (solicited local adverse events) were defined as events at the injection site. Local reactogenicity signs and symptoms included pain and/or tenderness proximal to the injection site.

  Up to 7 days after second vaccination on Day 84 (Day 91)

• Percentage of Participants With Local Reactogenicity Signs and Symptoms After Third Vaccination

  Percentage of participants with local reactogenicity signs and symptoms after third vaccination was reported. Local reactogenicity events (solicited local adverse events) were defined as events at the injection site. Local reactogenicity signs and symptoms included pain and/or tenderness proximal to the injection site.

  Up to 7 days after third vaccination on Day 168 (Up to Day 175)

• Percentage of Participants With Local Reactogenicity Signs and Symptoms After Fourth Vaccination

  Percentage of participants with local reactogenicity signs and symptoms after fourth vaccination was reported. Local reactogenicity events (solicited local adverse events) were defined as events at the injection site. Local reactogenicity signs and symptoms included pain and/or tenderness proximal to the injection site.

  Up to 7 days after fourth vaccination on Day 364 (Up to Day 371)

• Percentage of Participants With Systematic Reactogenicity Signs and Symptoms After First Vaccination

  Percentage of participants with systematic reactogenicity signs and symptoms after first vaccination was reported. Systemic reactogenicity events (solicited systemic adverse events) defined as events occurred in a predefined post-vaccination period for which the subject was specifically questioned. Systemic reactogenicity signs and symptoms included increased body temperature, malaise and/or fatigue, myalgia, headache, chills, arthralgia, nausea, and vomiting.

  Up to 7 days after first vaccination on Day 0 (Day 7)

• Percentage of Participants With Systematic Reactogenicity Signs and Symptoms After Second Vaccination

  Percentage of participants with systematic reactogenicity signs and symptoms after second vaccination was reported. Systemic reactogenicity events (solicited systemic adverse events) defined as events occurred in a predefined post-vaccination period for which the subject was specifically questioned. Systemic reactogenicity signs and symptoms included increased body temperature, malaise and/or fatigue, myalgia, headache, chills, arthralgia, nausea, and vomiting.

  Up to 7 days after second vaccination on Day 84 (Day 91)

• Percentage of Participants With Systematic Reactogenicity Signs and Symptoms After Third Vaccination

  Percentage of participants with systematic reactogenicity signs and symptoms after third vaccination was reported. Systemic reactogenicity events (solicited systemic adverse events) defined as events occurred in a predefined post-vaccination period for which the subject was specifically questioned. Systemic reactogenicity signs and symptoms included increased body temperature, malaise and/or fatigue, myalgia, headache, chills, arthralgia, nausea, and vomiting.

  Up to 7 days after third vaccination on Day 168 (Up to Day 175)

• Percentage of Participants With Systematic Reactogenicity Signs and Symptoms After Fourth Vaccination

  Percentage of participants with systematic reactogenicity signs and symptoms after fourth vaccination was reported. Systemic reactogenicity events (solicited systemic adverse events) defined as events occurred in a predefined post-vaccination period for which the subject was specifically questioned. Systemic reactogenicity signs and symptoms included increased body temperature, malaise and/or fatigue, myalgia, headache, chills, arthralgia, nausea, and vomiting.

  Up to 7 days after fourth vaccination on Day 364 (Up to Day 371)

• Percentage of Participants With Unsolicited Adverse Events (AEs) for 30 Days After First Vaccination

  An AE is any untoward medical occurrence in a clinical investigation participant administered a study product and which does not necessarily have a causal relationship with the study treatment. The most frequent unsolicited AEs were upper respiratory tract infection, back pain, cough, and hypertension.

  30 days after first vaccination on Day 0 (Up to Day 30)

• Percentage of Participants With Unsolicited AEs for 30 Days After Second Vaccination

  An AE is any untoward medical occurrence in a clinical investigation participant administered a study product and which does not necessarily have a causal relationship with the study treatment. The most frequent unsolicited AEs were upper respiratory tract infection, back pain, cough, and hypertension.

  30 days after second vaccination on Day 84 (Up to Day 114)

• Percentage of Participants With Unsolicited AEs for 30 Days After Third Vaccination

  An AE is any untoward medical occurrence in a clinical investigation participant administered a study product and which does not necessarily have a causal relationship with the study treatment. The most frequent unsolicited AEs were upper respiratory tract infection, back pain, cough, and hypertension.

  30 days after third vaccination on Day 168 (Up to Day 198)

• Percentage of Participants With Unsolicited AEs for 30 Days After Fourth Vaccination

  An AE is any untoward medical occurrence in a clinical investigation participant administered a study product and which does not necessarily have a causal relationship with the study treatment. The most frequent unsolicited AEs were upper respiratory tract infection, back pain, cough, and hypertension.

  30 days after fourth vaccination on Day 364 (Up to Day 394)

• Percentage of Participants With Serious Adverse Events (SAEs)

  An AE is any untoward medical occurrence in a clinical investigation participant administered a study product and which does not necessarily have a causal relationship with the study treatment. An SAE is any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is a suspected transmission of any infectious agent via a medicinal product.

  Up to Month 36 (up to end of the study)

• Percentage of Participants With Adverse Events of Special Interest (AESIs)

  Percentage of participants with AESIs was reported. Immune-mediated diseases were considered as AESIs in this study.

  Up to Month 36 (up to end of the study)

• Percentage of Participants With AEs Leading to Early Participant Withdrawal or Early Discontinuation of Study Product

  Percentage of participants with AEs leading to early participant withdrawal or early discontinuation of study product were reported. An AE is any untoward medical occurrence in a clinical investigation participant administered a study product and which does not necessarily have a causal relationship with this treatment.

  Up to Month 36 (up to end of the study)

Secondary Outcomes (7)

• Number of Participants With HIV-1 Infection Diagnosed From Enrollment (Baseline) Through Month 24 Post Enrollment

  Baseline up to Month 24

• Number of Participants With HIV-1 Infection Diagnosed From Enrollment (Baseline) Through Month 36 (End of Study) Post Enrollment

  Baseline up to Month 36 (End of study)

• Number of Participants With HIV-1 Infection Diagnosed From Month 13 Through Month 24 Post Enrollment

  Month 13 up to Month 24

• Number of Participants With HIV-1 Infection Diagnosed From Month 13 Through Month 36 (End of Study) Post Enrollment

  Month 13 up to Month 36 (End of study)

• Geometric Mean of Binding Antibody Responses to HIV Envelop (ENV) Clade (gp140) C (ZA) Analyzed by Enzyme-linked Immunosorbent Assay (ELISA)

  Months 0, 7, 13 and 24

Study Arms (2)

Group 1

EXPERIMENTAL

Participants will receive Ad26.Mos4.HIV 5\*10\^10 virus particles (vp) as 0.5 milliliter (mL) via Intramuscular (IM) injection into the left deltoid on Months 0, 3, 6, and 12 and Clade C gp140 (250 \[microgram\] mcg) mixed with Aluminum phosphate adjuvant as 0.5 mL IM into the right deltoid on Months 6 and 12.

Biological: Ad26.Mos4.HIV; Biological: Clade C gp140

Group 2

PLACEBO COMPARATOR

Participants will receive Placebo for Ad26.Mos4.HIV as 0.5 mL into the left deltoid on Months 0, 3, 6, and 12 and Placebo for Clade C gp140 / Aluminum phosphate adjuvant as 0.5 mL IM into the right deltoid on Months 6 and 12.

Biological: Placebo

Interventions

Ad26.Mos4.HIV BIOLOGICAL

Participants will receive Ad26.Mos4.HIV 5x10\^10 virus particles (vp) as 0.5 milliliter (mL) via Intramuscular (IM) into the left deltoid on Months 0, 3, 6, and 12.

Group 1

Clade C gp140 BIOLOGICAL

Participants will receive Clade C gp140 (250 mcg) mixed with Aluminum phosphate adjuvant as 0.5 mL IM into the right deltoid on Months 6 and 12.

Group 1

Placebo BIOLOGICAL

Participants will receive matching placebo.

Group 2

Eligibility Criteria

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

You may qualify if:

• Sexually active, defined as having had sexual intercourse with a male partner at least twice in the past 30 days prior to screening, and is considered by the site staff to be at risk for Human Immunodeficiency Virus (HIV) infection
• Access to a participating HIV Vaccine Trials Network (HVTN) Clinical Research Sites (CRS) and willingness to be followed for the planned duration of the study
• Willingness to discuss HIV infection risks and willing to receive HIV risk reduction counseling and appropriate referrals to minimize HIV acquisition, as applicable
• Negative beta human chorionic gonadotropin (beta-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
• Participants must also agree not to seek pregnancy through alternative methods, such as artificial insemination or in vitro fertilization until 3 months after the last vaccination

You may not qualify if:

• Investigational research agents received within 30 days before first vaccination
• HIV vaccine(s) received in a prior HIV vaccine trial. For volunteers who have received control/placebo in an HIV vaccine trial, the HVTN 705/HPX2008 (Protocol Safety Review Team) PSRT will determine eligibility on a case-by-case basis
• Live attenuated vaccines received within 30 days before first vaccination or scheduled within 14 days after injection (example: measles, mumps, and rubella \[MMR\]; oral polio vaccine \[OPV\]; varicella; yellow fever)
• Any vaccines that are not live attenuated vaccines and were received within 14 days prior to first vaccination (example, tetanus, pneumococcal, Hepatitis A or B)
• Immunosuppressive medications received within 6 months before first vaccination

Sponsors & Collaborators

• Janssen Vaccines & Prevention B.V.: lead

Study Sites (23)

UNC Lilongwe Project

Lilongwe, Malawi

Location

Polana Caniço Health Research and Training Center (CISPOC)

Maputo, Mozambique

Location

Josha Research

Bloemfontein, 9301, South Africa

Location

Masiphumelele Research Centre

Cape Town, 7975, South Africa

Location

Ndlovu Elandsdoorn Site

Dennilton, 0485, South Africa

Location

Perinatal HIV Research Unit, Chris Hani Baragwanath Hospital

Diepkloof, 1862, South Africa

Location

Perinatal HIV Research Unit, Chris Hani Baragwanath Hospital

Johannesburg, 1862, South Africa

Location

The Aurum Institute Klerksdorp Clinical Research Centre

Klerksdorp, 2571, South Africa

Location

Qhakaza Mbokodo Research Centre

KwaZulu-Natal, 4030, South Africa

Location

South African Medical Research Council Chatsworth Clinical Research Site

KwaZulu-Natal, 4030, South Africa

Location

Centre for the AIDS Programme of Research in South Africa

KwaZulu-Natal, 4110, South Africa

Location

South African Medical Research Council Tongaat Clinical Research Site

KwaZulu-Natal, 4399, South Africa

Location

Stanza Clinical Research Centre : Mamelodi

Mamelodi East, 122, South Africa

Location

Nelson Mandela Academic Clinical Research Unit 'NeMACRU'

Mthatha, 5099, South Africa

Location

MeCRU Clinical Research Unit

Pretoria, 204, South Africa

Location

The Aurum Institute Rustenburg Clinical Research Site

Rustenburg, 300, South Africa

Location

Setshaba Research Centre

Soshanguve, 152, South Africa

Location

The Aurum Institute: Tembisa - Clinic 4

Tembisa, 1632, South Africa

Location

Centre for Infectious Disease Research in Zambia (CIDRZ)

Lusaka, 10101, Zambia

Location

Center for Family Health Research in Zambia (CFHRZ)

Lusaka, P/BagE891, Zambia

Location

Center for Family Health Research in Zambia (CFHRZ)

Ndola, 240262, Zambia

Location

St Mary's Clinic

Chitungwiza, Zimbabwe

Location

University of Zimbabwe-UCSF

Harare - Seke South, Zimbabwe

Location

Related Publications (3)

• 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

• Gray GE, Mngadi K, Lavreys L, Nijs S, Gilbert PB, Hural J, Hyrien O, Juraska M, Luedtke A, Mann P, McElrath MJ, Odhiambo JA, Stieh DJ, van Duijn J, Takalani AN, Willems W, Tapley A, Tomaras GD, Van Hoof J, Schuitemaker H, Swann E, Barouch DH, Kublin JG, Corey L, Pau MG, Buchbinder S, Tomaka F; Imbokodo/HVTN 705/HPX2008 Study Group. Mosaic HIV-1 vaccine regimen in southern African women (Imbokodo/HVTN 705/HPX2008): a randomised, double-blind, placebo-controlled, phase 2b trial. Lancet Infect Dis. 2024 Nov;24(11):1201-1212. doi: 10.1016/S1473-3099(24)00358-X. Epub 2024 Jul 19.

  PMID: 39038477 DERIVED

• Barouch DH, Tomaka FL, Wegmann F, Stieh DJ, Alter G, Robb ML, Michael NL, Peter L, Nkolola JP, Borducchi EN, Chandrashekar A, Jetton D, Stephenson KE, Li W, Korber B, Tomaras GD, Montefiori DC, Gray G, Frahm N, McElrath MJ, Baden L, Johnson J, Hutter J, Swann E, Karita E, Kibuuka H, Mpendo J, Garrett N, Mngadi K, Chinyenze K, Priddy F, Lazarus E, Laher F, Nitayapan S, Pitisuttithum P, Bart S, Campbell T, Feldman R, Lucksinger G, Borremans C, Callewaert K, Roten R, Sadoff J, Scheppler L, Weijtens M, Feddes-de Boer K, van Manen D, Vreugdenhil J, Zahn R, Lavreys L, Nijs S, Tolboom J, Hendriks J, Euler Z, Pau MG, Schuitemaker H. Evaluation of a mosaic HIV-1 vaccine in a multicentre, randomised, double-blind, placebo-controlled, phase 1/2a clinical trial (APPROACH) and in rhesus monkeys (NHP 13-19). Lancet. 2018 Jul 21;392(10143):232-243. doi: 10.1016/S0140-6736(18)31364-3. Epub 2018 Jul 6.

  PMID: 30047376 DERIVED

Results Point of Contact

• Title: CLINICAL FRANCHISE LEADER
• Organization: Janssen Vaccines & Prevention B.V

ClinicalTrialDisclosure@its.jnj.com

844-434-4210

Study Officials

• Janssen Vaccines & Prevention B.V. Clinical Trial

  Janssen Vaccines & Prevention B.V.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Sponsor will be also blinded
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 17, 2017
• First Posted: February 23, 2017
• Study Start: November 3, 2017
• Primary Completion: February 2, 2022
• Study Completion: February 2, 2022
• Last Updated: April 18, 2023
• Results First Posted: April 18, 2023

Record last verified: 2023-03

Locations

ZA (3); MO (1); ZI (2); MA (1)