A Study of Heterologous Vaccine Regimen of Adenovirus Serotype 26 Mosaic4 Human Immunodeficiency Virus(Ad26.Mos4.HIV), Adjuvanted Clade C gp140 and Mosaic gp140 to Prevent HIV-1 Infection Among Cis-gender Men and Transgender Individuals Who Have Sex With Cis-gender Men and/or Transgender Individuals

Phase 3

Completed

Conditions: Healthy

Interventions: Biological: Ad26.Mos4.HIV
Biological: Placebo
Biological: Clade C and Mosaic gp140 HIV bivalent vaccine

Registration Number: NCT03964415

Lead Sponsor: Janssen Vaccines & Prevention B.V.

Brief Summary: The purpose of this study is to evaluate the vaccine efficacy (VE) of a heterologous vaccine regimen utilizing Ad26.Mos4.HIV and aluminum phosphate-adjuvanted Clade C gp140 and Mosaic gp140 for the prevention of HIV-1 infection in HIV-1 seronegative cis-gender men and transgender individuals having sex with cis-gender men and/or transgender individuals.

Detailed Description: Human immunodeficiency virus type 1 (HIV-1) is a retrovirus that, if left untreated, can progress to acquired immunodeficiency syndrome (AIDS), a condition in which the immune system is severely compromised, leading to life-threatening conditions. Ad26.Mos4.HIV is a tetravalent vaccine composed of Ad26.Mos1.Gag-Pol, Ad26.Mos2.Gag-Pol, Ad26.Mos1.Env, and Ad26.Mos2S.Env. Clade C and Mosaic gp140 HIV bivalent vaccine contains: Clade C gp140, HIV-1 Env gp140 of Clade C, Mosaic gp140, HIV-1 Env gp140, and aluminum phosphate adjuvant. Evidences showed that a combination of vaccination with Ad26.Mos.HIV followed by Ad26.Mos.HIV together with Clade C gp140 protein in aluminum phosphate adjuvant led to highest level of protection observed so far with this vaccine concept. Study comprises of a screening period of 45 days, a 12-month vaccination period and a follow-up period of at least 18 months after fourth vaccination (until Month 30) in participants who remain HIV-1 negative or up to 6 months after diagnosis of HIV-1 infection in participants who become HIV-1 infected. Participants who completed their Month 30 visit will be followed for HIV infection, medically-attended adverse event (MAAEs) and serious adverse events until the end of study (Month 30). Primary analysis of vaccine efficacy will evaluate the number of HIV-1 infections in the vaccine group compared to number of HIV-1 infections in the placebo group between Month 7 and Month X (with 24\<=X\<=30) in per-protocol population.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 3900

Inclusion Criteria

Individual is either cis-gender man having sex with cis-gender men and/or transgender individuals or transgender woman having sex with cis-gender men and/or transgender individuals or transgender man having sex with cis-gender men and/or transgender women or gender non-conforming individual having receptive or insertive anal and/or vaginal condom-less intercourse and who is considered by the site staff to be at increased risk for HIV-1 infection. The potential participants must in the last 6 months have had any condom-less receptive anal or vaginal sex (not included is condom-less anal sex within a mutually monogamous relationship >=12 months if the partner is HIV negative or living with HIV and virally suppressed) or rectal or urethral gonorrhea or chlamydia or incident syphilis or any stimulant use or any other drug and/or substance which in the local context may be associated with increased HIV transmission (example, cocaine, amphetamine) or 5 or more sex partners
Potential participant has a negative test result for HIV-1 and HIV-2 infection less than or equal to (<=) 28 days prior to first vaccination
Potential participant must be healthy based on medical history, physical examination, and vital sign measurement performed at screening
Contraceptive use by participants assigned female at birth and who have not had sexual reassignment surgery should be consistent with local regulations regarding the acceptable methods of contraception for those participating in clinical studies
All participants of childbearing potential must have a negative serum beta-human chorionic gonadotropin (beta-hCG) pregnancy test at screening and have a negative urine beta-hCG pregnancy test immediately prior to each study vaccine administration

Exclusion Criteria

Potential participants choosing to use PrEP. However, once participants are enrolled and received their first vaccination, and they change their mind regarding PrEP usage, they will be allowed to take PrEP according to the site PrEP plan and will continue to receive further vaccinations. The use of long acting PrEP is disallowed from 24 months prior to Day 1
Potential participant is a recipient of a HIV-vaccine candidate at any time, or a recipient of other experimental vaccine(s) within the last 12 months prior to Day 1. For participants who received an experimental vaccine (except HIV vaccine) more than 12 months prior to Day 1, documentation of the identity of the experimental vaccine must be provided to the HPX3002/HVTN 706 safety review team, who will determine eligibility on a case by-case basis. Exceptions: participants can be included if the vaccine received (except HIV vaccine) was subsequently licensed or authorized for emergency use (example, Emergency Use Authorization (EUA), Emergency Use Listing (EUL), or similar program). Participants with proof of having received only placebo can also be included. Participants who are currently still in an interventional study of such a licensed/emergency use-authorized vaccine are to be excluded from the current study
Potential participant has received an HIV-related mAb, whether licensed or investigational, within the last 12 months prior to Day 1. For participants who received an HIV-related mAb more than 12 months prior to Day 1, documentation of the identity of the mAb must be provided to the HPX3002/HVTN 706 safety review team, who will determine eligibility on a case-by-case basis
Potential participant has known allergy or history of anaphylaxis or other serious adverse reactions to vaccines
Pregnant, or breast-feeding, or planning to become pregnant while enrolled in this study or within 90 days after the last dose of study vaccination

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group1:Ad26.Mos4.HIV,Clade C and Mosaic gp140 bivalent vaccine	Ad26.Mos4.HIV	Participants will receive adenovirus serotype 26.Mosaic 4.human immunodeficiency virus (Ad26.Mos4.HIV) via intramuscular (IM) injection into the deltoid muscle at months 0 (Day 1) and 3 (preferably the deltoid of the non-dominant upper arm) and, Ad26.Mos4.HIV together with Clade C and Mosaic gp140 HIV bivalent vaccine IM into the deltoid muscle at Months 6 and 12 (different deltoid for each injection).
Group1:Ad26.Mos4.HIV,Clade C and Mosaic gp140 bivalent vaccine	Clade C and Mosaic gp140 HIV bivalent vaccine	Participants will receive adenovirus serotype 26.Mosaic 4.human immunodeficiency virus (Ad26.Mos4.HIV) via intramuscular (IM) injection into the deltoid muscle at months 0 (Day 1) and 3 (preferably the deltoid of the non-dominant upper arm) and, Ad26.Mos4.HIV together with Clade C and Mosaic gp140 HIV bivalent vaccine IM into the deltoid muscle at Months 6 and 12 (different deltoid for each injection).
Group 2: Placebo	Placebo	Participants will receive placebo into the deltoid muscle on Months 0 (Day 1), 3 (1 injection), 6 and 12 (2 injections).

Primary Outcome Measures

Name	Time	Method
Number of Participants With Confirmed Human Immunodeficiency Virus (HIV)-1 Infections Diagnosed Between the Month 7 and Month 24 Visits (Per-protocol [PP] Set)	From Month 7 up to Month 24	Number of participants with a confirmed HIV-1 infections diagnosed between the Month 7 and Month 24 visits (PP set) was reported. The data represents the cumulative incidence of HIV-1 infections.
Number of Participants With a Confirmed Human Immunodeficiency Virus (HIV)-1 Infections Diagnosed Between the Month 7 and Month 30 Visits (PP Set)	From Month 7 up to Month 30	Number of participants with a confirmed HIV-1 infections diagnosed between the Month 7 and Month 30 visits (PP set) was reported. The data represents the cumulative incidence of HIV-1 infections.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Solicited Systemic Adverse Events (AEs)	Up to 7 days after each vaccination (dose) on Days 1 (up to Day 8), 84 (up to Day 91), 168 (up to Day 175), and 364 (up to 371)	Number of participants with solicited systemic AEs were reported. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. Solicited systemic events included events such as fatigue, headache, nausea, and myalgia, for which participants were specifically questioned and which were noted by participants in their participant diary for 7 days post vaccination (day of vaccination and the subsequent 7 days).
Number of Participants With Unsolicited Adverse Events (AEs)	Up to 28 days after each vaccination (dose) on Days 1 (up to Day 29), 84 (up to Day 112), 168 (up to Day 196), and 364 (up to 392)	Number of participants with unsolicited AEs were reported. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. Unsolicited AEs are all AEs for which the participants were not specifically questioned in the participant's diary.
Number of Participants With Adverse Events of Special Interest (AESIs)	Up to 6 months after the last vaccination (up to Month 18)	Number of participants with AESIs were reported. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. Thrombotic events and/or thrombocytopenia (defined as platelet count below the lower limit of normal \[LLN\] range for the testing lab) were considered to be potential AESIs.
Number of Participants With Solicited Local Adverse Events (AEs)	Up to 7 days post each vaccination (dose) on Days 1 (up to Day 8), 84 (up to Day 91), 168 (up to Day 175), and 364 (up to 371)	Number of participants with solicited local AEs were reported. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. Solicited local AEs that included injection site pain/tenderness, erythema and swelling at the study vaccine injection site, are used to assess the reactogenicity of the study vaccine and are pre-defined local (injection site) and which were noted by participants in their participant diary for 7 days post vaccination (day of vaccination and the subsequent 7 days).
Number of Participants With Medically-attended Adverse Events (MAAEs)	From Day 1 up to Month 40	Number of participants with MAAEs were reported. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. MAAEs are defined as AEs with medically-attended visits including hospital, emergency room, urgent care clinic, or other visits to or from medical personnel for any reason.
Number of Participants With Serious Adverse Events (SAEs)	From Day 1 up to Month 40	Number of participants with SAEs were reported. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly/birth defect; suspected transmission of any infectious agent via a medicinal product or medically important.
Number of Participants Who Discontinued the Study or Study Intervention Due to Adverse Events (AEs)	From Day 1 up to Month 40	Number of participants who discontinued the study or study intervention due to AEs were reported. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study.
Number of Participants With a Confirmed Human Immunodeficiency Virus (HIV)-1 Infections Diagnosed Over Time (Modified Intent-to-Treat [mITT] Set)	Month 0 to 24, Month 0 to 30, Month 0 to 40	Number of participants with a confirmed HIV-1 infections diagnosed over time (mITT set) were reported. The data represents the cumulative incidence of HIV-1 infections at specified intervals.
Number of Participants With a Confirmed Human Immunodeficiency Virus (HIV)-1 Infections Diagnosed Over Time (Modified Intent-to-Treat-2 [mITT-2] Set)	Month 7 to 24, Month 7 to 30, Month 7 to 40	Number of participants with a confirmed HIV-1 infections diagnosed over time (mITT-2 set) were reported. The data represents the cumulative incidence of HIV-1 infections at specified intervals.
Number of Participants With Confirmed Human Immunodeficiency Virus (HIV)-1 Infections as Assessed by Demographic Characteristics: Age Groups	Month 7 to 24, Month 7 to 30, Month 7 to 40	Number of participants with confirmed HIV-1 infection as assessed by demographic characteristics: age groups was reported. Age groups included 18-20, 21-24, 25-29, 30-34, 35-44, and greater than or equal to (\>=) 45 years. The data represents the cumulative incidence of HIV-1 infections at specified intervals.
Number of Participants With an HIV-1 Infection by Adenovirus Serotype 26 (Ad26) at Baseline	Baseline (Day 1)	Number of participants with an HIV-1 infection by Ad26 at baseline were reported.
Number of Participants With Confirmed Human Immunodeficiency Virus (HIV)-1 Infections Diagnosed Over Time (Modified Intent-to-Treat-3 [mITT-3] Set)	Month 7 to 24, Month 7 to 30, Month 7 to 40	Number of participants with confirmed HIV-1 infection diagnosed over time (mITT-3 set) were reported. The data represents the cumulative incidence of HIV-1 infections at specified intervals.
Number of Participants With Confirmed Human Immunodeficiency Virus (HIV)-1 Infections Diagnosed Over Time (Full Immunization Analysis Set [FIS])	Month 13 to 24, Month 13 to 30, Month 13 to 40	Number of participants with confirmed HIV-1 infection diagnosed over time (FIS set) were reported. The data represents the cumulative incidence of HIV-1 infections at specified intervals.
Number of Participants With Confirmed Human Immunodeficiency Virus (HIV)-1 Infections as Assessed by Demographic Characteristics: Region-Wise Enrollment	Month 7 to 24, Month 7 to 30, Month 7 to 40	Number of participants with confirmed HIV-1 infections as assessed by demographic characteristics: region-wise enrollment was reported. Regions were Latin-America (Argentina, Brazil, Mexico, and Peru), North America (Puerto Rico and United States of America), and Europe (Italy, Poland, and Spain). The data represents the cumulative incidence of HIV-1 infections at specified intervals.
Geometric Mean Antibody Titers For Adenovirus Serotype 26 (Ad26) as Determined by Vector Neutralization Assay (VNA)	From Day 1 up to Month 40	Geometric mean antibody titers for Ad26 as determined by VNA were reported.
Number of Participants With HIV-1 Infection by Pre/Post-exposure Prophylaxis (P[r]EP) Use	Month 7 to 24, Month 7 to 30, Month 7 to 40	Number of participants with HIV-1 infection by P(r)EP use were reported. P(r)EP was assessed with a 4 item survey. Each item was measured on a scale ranging from 1 (strongly disagree) to 5 (strongly agree). Higher scores indicating higher levels of self-efficacy. If participant showed any evidence of P(r)EP use during the period based on questionnaire responses, concomitant medications or dried blood spot analysis, the response was "yes". The data represents the cumulative incidence of HIV-1 infections at specified intervals.

Trial Locations

Locations (53): University of Pennsylvania
🇺🇸
Philadelphia, Pennsylvania, United States
Dana-Farber/Brigham and Women's Hospital
🇺🇸
Boston, Massachusetts, United States
Seattle Vaccine Trials Unit
🇺🇸
Seattle, Washington, United States
Whitman Walker Health
🇺🇸
Washington, District of Columbia, United States
Orlando Immunology Center
🇺🇸
Orlando, Florida, United States
Emory University Rollins School of Public Health - Ponce De Leon CRS
🇺🇸
Atlanta, Georgia, United States
University Of Illinois
🇺🇸
Chicago, Illinois, United States
The Hope Clinic at Emory University
🇺🇸
Decatur, Georgia, United States
New Orleans Adolescent Trials Unit CRS
🇺🇸
New Orleans, Louisiana, United States
Fenway Health
🇺🇸
Boston, Massachusetts, United States
Harlem Prevention Center CRS
🇺🇸
New York, New York, United States
Rutgers, The State University of New Jersey - The University Hospital/ACTG Network
🇺🇸
Newark, New Jersey, United States
Columbia University Medical Center
🇺🇸
New York, New York, United States
Strong Memorial Infectious Disease
🇺🇸
Rochester, New York, United States
New York Blood Center
🇺🇸
New York, New York, United States
Gordon E. Crofoot MD
🇺🇸
Houston, Texas, United States
Helios Salud Sa
🇦🇷
Buenos Aires, Argentina
Fundacion Huesped
🇦🇷
Ciudad Autonoma De Buenos Aire, Argentina
Instituto Caici Srl.
🇦🇷
Rosario, Argentina
Universidade Federal De Minas Gerais - Hospital das Clínicas
🇧🇷
Belo Horizonte, Brazil
Hospital J. M. Ramos Mejía
🇦🇷
Ciudad de Buenos Aires, Argentina
Fundacao de Medicina Tropical Doutor Heitor Vieira Dourado - FMT
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Manaus, Brazil
Centro Medico Sao Francisco
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Curitiba, Brazil
Fundacao Oswaldo Cruz
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Rio de Janeiro, Brazil
Municipio de Nova Iguacu - Hospital Geral de Nova Iguacu
🇧🇷
Rio de Janeiro, Brazil
Instituto de infectologia Emilio Ribas
🇧🇷
Sao Paulo, Brazil
Hospital Das Clinicas Da Faculdade De Medicina Da USP
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Sao Paulo, Brazil
Centro de Referencia E Treinamento Dst/Aids
🇧🇷
Sao Paulo, Brazil
Ospedale San Raffaele
🇮🇹
Milano, Italy
Azienda Ospedaliero-Universitaria Policlinico di Modena
🇮🇹
Modena, Italy
Hospital Civil Fray Antonio Alcalde
🇲🇽
Guadalajara, Mexico
Istituto nazionale malattie infettive 'L. Spallanzani'
🇮🇹
Roma, Italy
Inst. Nal. de Ciencias Med. Y Nutricion Salvador Zubiran
🇲🇽
Mexico City, Mexico
Unidad de Atención Medica e Investigacion en Salud (UNAMIS)
🇲🇽
Merida, Mexico
Centro de Investigaciones Tecnologicas, Biomedica y medio ambientales (CITBM)
🇵🇪
Callao, Peru
Neutrum Lekarze M.Hlebowicz i Partnerzy spolka partnerska
🇵🇱
Gdansk, Poland
Wroclawskie Centrum Zdrowia SPZOZ, Poradnia Profilaktyczno-Lecznicza
🇵🇱
Wroclaw, Poland
Clinical Research Puerto Rico Inc
🇵🇷
San Juan, Puerto Rico
University of Puerto Rico
🇵🇷
San Juan, Puerto Rico
Hosp. Univ. Germans Trias I Pujol
🇪🇸
Badalona, Spain
Hosp. Univ. Vall D Hebron
🇪🇸
Barcelona, Spain
Hosp Reina Sofia
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Cordoba, Spain
Hosp Univ Fund Jimenez Diaz
🇪🇸
Madrid, Spain
Hosp. Gral. Univ. Valencia
🇪🇸
Valencia, Spain
Hosp. Clinico San Carlos
🇪🇸
Madrid, Spain
Bridge HIV
🇺🇸
San Francisco, California, United States
University of Miami
🇺🇸
Miami, Florida, United States
Vanderbilt University Medical Center
🇺🇸
Nashville, Tennessee, United States
Asociacion Civil Selva Amazonica (ACSA)
🇵🇪
Iquitos, Peru
Asociacion Civil Impacta Salud y Educacion- San Miguel CRS
🇵🇪
Lima - San Miguel, Peru
Asociacion Civil Via Libre
🇵🇪
Lima, Peru
Asociacion Civil Impacta Salud y Educacion - Barranco
🇵🇪
Lima - Barranco, Peru
University of Alabama at Birmingham
🇺🇸
Birmingham, Alabama, United States