Clinical trial NCT03964415: 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
Official title: A Multi-center, Randomized, Double-blind, Placebo-controlled Phase 3 Efficacy Study of a Heterologous Vaccine Regimen of Ad26.Mos4.HIV and 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Healthy
Lead sponsor: Janssen Vaccines & Prevention B.V.
Sponsor class: INDUSTRY
First posted: 2019-05-28
Enrollment: 3900
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants With Confirmed Human Immunodeficiency Virus (HIV)-1 Infections Diagnosed Between the Month 7 and Month 24 Visits (Per-protocol [PP] Set)
timeFrame: From Month 7 up to Month 24
measure: Number of Participants With a Confirmed Human Immunodeficiency Virus (HIV)-1 Infections Diagnosed Between the Month 7 and Month 30 Visits (PP Set)
timeFrame: From Month 7 up to Month 30
Secondary outcomes:
measure: Number of Participants With Solicited Local Adverse Events (AEs)
timeFrame: 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)
measure: Number of Participants With Solicited Systemic Adverse Events (AEs)
timeFrame: 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)
measure: Number of Participants With Unsolicited Adverse Events (AEs)
timeFrame: 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)
measure: Number of Participants With Adverse Events of Special Interest (AESIs)
timeFrame: Up to 6 months after the last vaccination (up to Month 18)
measure: Number of Participants With Medically-attended Adverse Events (MAAEs)
timeFrame: From Day 1 up to Month 40
measure: Number of Participants With Serious Adverse Events (SAEs)
timeFrame: From Day 1 up to Month 40
measure: Number of Participants Who Discontinued the Study or Study Intervention Due to Adverse Events (AEs)
timeFrame: From Day 1 up to Month 40
measure: Number of Participants With a Confirmed Human Immunodeficiency Virus (HIV)-1 Infections Diagnosed Over Time (Modified Intent-to-Treat [mITT] Set)
timeFrame: Month 0 to 24, Month 0 to 30, Month 0 to 40
measure: Number of Participants With a Confirmed Human Immunodeficiency Virus (HIV)-1 Infections Diagnosed Over Time (Modified Intent-to-Treat-2 [mITT-2] Set)
timeFrame: Month 7 to 24, Month 7 to 30, Month 7 to 40
measure: Number of Participants With Confirmed Human Immunodeficiency Virus (HIV)-1 Infections Diagnosed Over Time (Modified Intent-to-Treat-3 [mITT-3] Set)
timeFrame: Month 7 to 24, Month 7 to 30, Month 7 to 40
measure: Number of Participants With Confirmed Human Immunodeficiency Virus (HIV)-1 Infections Diagnosed Over Time (Full Immunization Analysis Set [FIS])
timeFrame: Month 13 to 24, Month 13 to 30, Month 13 to 40
measure: Number of Participants With Confirmed Human Immunodeficiency Virus (HIV)-1 Infections as Assessed by Demographic Characteristics: Age Groups
timeFrame: Month 7 to 24, Month 7 to 30, Month 7 to 40
measure: Number of Participants With Confirmed Human Immunodeficiency Virus (HIV)-1 Infections as Assessed by Demographic Characteristics: Region-Wise Enrollment
timeFrame: Month 7 to 24, Month 7 to 30, Month 7 to 40
measure: Number of Participants With an HIV-1 Infection by Adenovirus Serotype 26 (Ad26) at Baseline
timeFrame: Baseline (Day 1)
measure: Geometric Mean Antibody Titers For Adenovirus Serotype 26 (Ad26) as Determined by Vector Neutralization Assay (VNA)
timeFrame: From Day 1 up to Month 40
measure: Number of Participants With HIV-1 Infection by Pre/Post-exposure Prophylaxis (P[r]EP) Use
timeFrame: Month 7 to 24, Month 7 to 30, Month 7 to 40
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: San Francisco
country: United States
facility: Bridge HIV
state: California
city: Washington
country: United States
facility: Whitman Walker Health
state: District of Columbia
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Orlando
country: United States
facility: Orlando Immunology Center
state: Florida
city: Atlanta
country: United States
facility: Emory University Rollins School of Public Health - Ponce De Leon CRS
state: Georgia
city: Decatur
country: United States
facility: The Hope Clinic at Emory University
state: Georgia
city: Chicago
country: United States
facility: University Of Illinois
state: Illinois
city: New Orleans
country: United States
facility: New Orleans Adolescent Trials Unit CRS
state: Louisiana
city: Boston
country: United States
facility: Dana-Farber/Brigham and Women's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Fenway Health
state: Massachusetts
city: Newark
country: United States
facility: Rutgers, The State University of New Jersey - The University Hospital/ACTG Network
state: New Jersey
city: New York
country: United States
facility: Harlem Prevention Center CRS
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: New York
country: United States
facility: New York Blood Center
state: New York
city: Rochester
country: United States
facility: Strong Memorial Infectious Disease
state: New York
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Houston
country: United States
facility: Gordon E. Crofoot MD
state: Texas
city: Seattle
country: United States
facility: Seattle Vaccine Trials Unit
state: Washington
city: Buenos Aires
country: Argentina
facility: Helios Salud Sa
city: Ciudad Autonoma De Buenos Aire
country: Argentina
facility: Fundacion Huesped
city: Ciudad de Buenos Aires
country: Argentina
facility: Hospital J. M. Ramos Mejía
city: Rosario
country: Argentina
facility: Instituto Caici Srl.
city: Belo Horizonte
country: Brazil
facility: Universidade Federal De Minas Gerais - Hospital das Clínicas
city: Curitiba
country: Brazil
facility: Centro Medico Sao Francisco
city: Manaus
country: Brazil
facility: Fundacao de Medicina Tropical Doutor Heitor Vieira Dourado - FMT
city: Rio de Janeiro
country: Brazil
facility: Fundacao Oswaldo Cruz
city: Rio de Janeiro
country: Brazil
facility: Municipio de Nova Iguacu - Hospital Geral de Nova Iguacu
city: Sao Paulo
country: Brazil
facility: Instituto de infectologia Emilio Ribas
city: Sao Paulo
country: Brazil
facility: Hospital Das Clinicas Da Faculdade De Medicina Da USP
city: Sao Paulo
country: Brazil
facility: Centro de Referencia E Treinamento Dst/Aids
city: Milano
country: Italy
facility: Ospedale San Raffaele
city: Modena
country: Italy
facility: Azienda Ospedaliero-Universitaria Policlinico di Modena
city: Roma
country: Italy
facility: Istituto nazionale malattie infettive 'L. Spallanzani'
city: Guadalajara
country: Mexico
facility: Hospital Civil Fray Antonio Alcalde
city: Merida
country: Mexico
facility: Unidad de Atención Medica e Investigacion en Salud (UNAMIS)
city: Mexico City
country: Mexico
facility: Inst. Nal. de Ciencias Med. Y Nutricion Salvador Zubiran
city: Callao
country: Peru
facility: Centro de Investigaciones Tecnologicas, Biomedica y medio ambientales (CITBM)
city: Iquitos
country: Peru
facility: Asociacion Civil Selva Amazonica (ACSA)
city: Lima - Barranco
country: Peru
facility: Asociacion Civil Impacta Salud y Educacion - Barranco
city: Lima - San Miguel
country: Peru
facility: Asociacion Civil Impacta Salud y Educacion- San Miguel CRS
city: Lima
country: Peru
facility: Asociacion Civil Via Libre
city: Gdansk
country: Poland
facility: Neutrum Lekarze M.Hlebowicz i Partnerzy spolka partnerska
city: Wroclaw
country: Poland
facility: Wroclawskie Centrum Zdrowia SPZOZ, Poradnia Profilaktyczno-Lecznicza
city: San Juan
country: Puerto Rico
facility: Clinical Research Puerto Rico Inc
city: San Juan
country: Puerto Rico
facility: University of Puerto Rico
city: Badalona
country: Spain
facility: Hosp. Univ. Germans Trias I Pujol
city: Barcelona
country: Spain
facility: Hosp. Univ. Vall D Hebron
city: Cordoba
country: Spain
facility: Hosp Reina Sofia
city: Madrid
country: Spain
facility: Hosp Univ Fund Jimenez Diaz
city: Madrid
country: Spain
facility: Hosp. Clinico San Carlos
city: Valencia
country: Spain
facility: Hosp. Gral. Univ. Valencia
Study officials:
affiliation: Janssen Vaccines & Prevention B.V.
name: Janssen Vaccines & Prevention B.V. Clinical Trial
role: STUDY_DIRECTOR
References: