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

Phase 2

Terminated

Conditions: HIV-1

Interventions: Biological: Ad26.Mos4.HIV
Biological: Placebo
Biological: Clade C gp140

Registration Number: NCT03060629

Lead Sponsor: Janssen Vaccines & Prevention B.V.

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: Female

Target Recruitment: 2636

Inclusion Criteria

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

Exclusion Criteria

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group 1	Clade C gp140	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.
Group 1	Ad26.Mos4.HIV	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.
Group 2	Placebo	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.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Human Immuno Deficiency Virus-1 (HIV-1) Infection Diagnosed Between Month 7 to Month 24 Post Enrollment	Month 7 up to Month 24	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.
Percentage of Participants With Local Reactogenicity Signs and Symptoms After First Vaccination	Up to 7 days after first vaccination on Day 0 (Day 7)	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.
Percentage of Participants With Local Reactogenicity Signs and Symptoms After Second Vaccination	Up to 7 days after second vaccination on Day 84 (Day 91)	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.
Percentage of Participants With Local Reactogenicity Signs and Symptoms After Third Vaccination	Up to 7 days after third vaccination on Day 168 (Up to Day 175)	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.
Percentage of Participants With Local Reactogenicity Signs and Symptoms After Fourth Vaccination	Up to 7 days after fourth vaccination on Day 364 (Up to Day 371)	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.
Percentage of Participants With Systematic Reactogenicity Signs and Symptoms After First Vaccination	Up to 7 days after first vaccination on Day 0 (Day 7)	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.
Percentage of Participants With Systematic Reactogenicity Signs and Symptoms After Second Vaccination	Up to 7 days after second vaccination on Day 84 (Day 91)	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.
Percentage of Participants With Systematic Reactogenicity Signs and Symptoms After Third Vaccination	Up to 7 days after third vaccination on Day 168 (Up to Day 175)	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.
Percentage of Participants With Systematic Reactogenicity Signs and Symptoms After Fourth Vaccination	Up to 7 days after fourth vaccination on Day 364 (Up to Day 371)	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.
Percentage of Participants With Unsolicited Adverse Events (AEs) for 30 Days After First Vaccination	30 days after first vaccination on Day 0 (Up to Day 30)	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.
Percentage of Participants With Unsolicited AEs for 30 Days After Second Vaccination	30 days after second vaccination on Day 84 (Up to Day 114)	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.
Percentage of Participants With Unsolicited AEs for 30 Days After Fourth Vaccination	30 days after fourth vaccination on Day 364 (Up to Day 394)	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.
Percentage of Participants With Serious Adverse Events (SAEs)	Up to Month 36 (up to end of the study)	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.
Percentage of Participants With Adverse Events of Special Interest (AESIs)	Up to Month 36 (up to end of the study)	Percentage of participants with AESIs was reported. Immune-mediated diseases were considered as AESIs in this study.
Percentage of Participants With AEs Leading to Early Participant Withdrawal or Early Discontinuation of Study Product	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 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.
Percentage of Participants With Unsolicited AEs for 30 Days After Third Vaccination	30 days after third vaccination on Day 168 (Up to Day 198)	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.

Secondary Outcome Measures

Name	Time	Method
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 24 post enrollment was reported. The data represents the cumulative incidence of HIV-1 infections.
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 enrollment (baseline) through Month 36 post enrollment was reported. The data represents the cumulative incidence of HIV-1 infections.
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 24 post enrollment was reported. The data represents the cumulative incidence of HIV-1 infections.
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)	Number of participants with HIV-1 infection diagnosed from Month 13 through Month 36 (end of study) post enrollment was reported. The data represents the cumulative incidence of HIV-1 infections.
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	A weighted geometric mean of the binding antibody responses to HIV envelope (ENV) gp140 Clade C 97ZA protein analyzed by ELISA was reported.
Geometric Mean of Interferon-gamma (IFN-gamma) T-Cells Responses Analyzed by Enzyme-linked Immunospot Assay (ELISpot)	Months 0, 7, 13 and 24	Geometric mean of IFN-gamma T-cells responses analyzed by ELISpot were reported. A weighted geometric mean of the number of spot-forming cells (SFC) per million peripheral blood mononuclear cells (PBMCs) producing Interferon-gamma upon stimulation with potential T-cell epitope (PTE) ENV peptide pools analyzed by ELISpot was reported. Reported responses are the sum of the number of SFCs/10\^6 PBMCS for PTE Env1, Env2 and Env3 sub-pools.
Number of Participants With Viral Sequences	Month 7 up to Month 24	Number of participants with viral sequences were reported. Viral sequencing was conducted on the earliest available plasma specimens with positive HIV-1 ribose nucleic acid polymerase chain reaction (RNA PCR) tests from study participants who were diagnosed with HIV-1 infection.

Trial Locations

Locations (21): Masiphumelele Research Centre
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Cape Town, South Africa
St Mary's Clinic
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Chitungwiza, Zimbabwe
UNC Lilongwe Project
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Lilongwe, Malawi
The Aurum Institute Klerksdorp Clinical Research Centre
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Klerksdorp, South Africa
South African Medical Research Council Chatsworth Clinical Research Site
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KwaZulu-Natal, South Africa
Center for Family Health Research in Zambia (CFHRZ)
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Ndola, Zambia
Nelson Mandela Academic Clinical Research Unit 'NeMACRU'
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Mthatha, South Africa
MeCRU Clinical Research Unit
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Pretoria, South Africa
Setshaba Research Centre
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Soshanguve, South Africa
University of Zimbabwe-UCSF
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Harare - Seke South, Zimbabwe
Qhakaza Mbokodo Research Centre
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KwaZulu-Natal, South Africa
Centre for the AIDS Programme of Research in South Africa
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KwaZulu-Natal, South Africa
South African Medical Research Council Tongaat Clinical Research Site
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KwaZulu-Natal, South Africa
Stanza Clinical Research Centre : Mamelodi
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Mamelodi East, South Africa
The Aurum Institute: Tembisa - Clinic 4
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Tembisa, South Africa
The Aurum Institute Rustenburg Clinical Research Site
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Rustenburg, South Africa
Ndlovu Elandsdoorn Site
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Dennilton, South Africa
Josha Research
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Bloemfontein, South Africa
Perinatal HIV Research Unit, Chris Hani Baragwanath Hospital
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Johannesburg, South Africa
Polana Caniço Health Research and Training Center (CISPOC)
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Maputo, Mozambique
Centre for Infectious Disease Research in Zambia (CIDRZ)
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Lusaka, Zambia