Clinical trial NCT03060629: 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
Official title: A Multicenter, Randomized, Double-blind, Placebo-controlled Phase 2b Efficacy Study of a Heterologous Prime/Boost Vaccine Regimen of Ad26.Mos4.HIV and Aluminum Phosphate-adjuvanted Clade C gp140 in Preventing HIV-1 Infection in Adult Women in Sub-Saharan Africa
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: HIV-1
Lead sponsor: Janssen Vaccines & Prevention B.V.
Sponsor class: INDUSTRY
First posted: 2017-02-23
Enrollment: 2636
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.


Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants With Human Immuno Deficiency Virus-1 (HIV-1) Infection Diagnosed Between Month 7 to Month 24 Post Enrollment
timeFrame: Month 7 up to Month 24
measure: Percentage of Participants With Local Reactogenicity Signs and Symptoms After First Vaccination
timeFrame: Up to 7 days after first vaccination on Day 0 (Day 7)
measure: Percentage of Participants With Local Reactogenicity Signs and Symptoms After Second Vaccination
timeFrame: Up to 7 days after second vaccination on Day 84 (Day 91)
measure: Percentage of Participants With Local Reactogenicity Signs and Symptoms After Third Vaccination
timeFrame: Up to 7 days after third vaccination on Day 168 (Up to Day 175)
measure: Percentage of Participants With Local Reactogenicity Signs and Symptoms After Fourth Vaccination
timeFrame: Up to 7 days after fourth vaccination on Day 364 (Up to Day 371)
measure: Percentage of Participants With Systematic Reactogenicity Signs and Symptoms After First Vaccination
timeFrame: Up to 7 days after first vaccination on Day 0 (Day 7)
measure: Percentage of Participants With Systematic Reactogenicity Signs and Symptoms After Second Vaccination
timeFrame: Up to 7 days after second vaccination on Day 84 (Day 91)
measure: Percentage of Participants With Systematic Reactogenicity Signs and Symptoms After Third Vaccination
timeFrame: Up to 7 days after third vaccination on Day 168 (Up to Day 175)
measure: Percentage of Participants With Systematic Reactogenicity Signs and Symptoms After Fourth Vaccination
timeFrame: Up to 7 days after fourth vaccination on Day 364 (Up to Day 371)
measure: Percentage of Participants With Unsolicited Adverse Events (AEs) for 30 Days After First Vaccination
timeFrame: 30 days after first vaccination on Day 0 (Up to Day 30)
measure: Percentage of Participants With Unsolicited AEs for 30 Days After Second Vaccination
timeFrame: 30 days after second vaccination on Day 84 (Up to Day 114)
measure: Percentage of Participants With Unsolicited AEs for 30 Days After Third Vaccination
timeFrame: 30 days after third vaccination on Day 168 (Up to Day 198)
measure: Percentage of Participants With Unsolicited AEs for 30 Days After Fourth Vaccination
timeFrame: 30 days after fourth vaccination on Day 364 (Up to Day 394)
measure: Percentage of Participants With Serious Adverse Events (SAEs)
timeFrame: Up to Month 36 (up to end of the study)
measure: Percentage of Participants With Adverse Events of Special Interest (AESIs)
timeFrame: Up to Month 36 (up to end of the study)
measure: Percentage of Participants With AEs Leading to Early Participant Withdrawal or Early Discontinuation of Study Product
timeFrame: Up to Month 36 (up to end of the study)
Secondary outcomes:
measure: Number of Participants With HIV-1 Infection Diagnosed From Enrollment (Baseline) Through Month 24 Post Enrollment
timeFrame: Baseline up to Month 24
measure: Number of Participants With HIV-1 Infection Diagnosed From Enrollment (Baseline) Through Month 36 (End of Study) Post Enrollment
timeFrame: Baseline up to Month 36 (End of study)
measure: Number of Participants With HIV-1 Infection Diagnosed From Month 13 Through Month 24 Post Enrollment
timeFrame: Month 13 up to Month 24
measure: Number of Participants With HIV-1 Infection Diagnosed From Month 13 Through Month 36 (End of Study) Post Enrollment
timeFrame: Month 13 up to Month 36 (End of study)
measure: Geometric Mean of Binding Antibody Responses to HIV Envelop (ENV) Clade (gp140) C (ZA) Analyzed by Enzyme-linked Immunosorbent Assay (ELISA)
timeFrame: Months 0, 7, 13 and 24
measure: Geometric Mean of Interferon-gamma (IFN-gamma) T-Cells Responses Analyzed by Enzyme-linked Immunospot Assay (ELISpot)
timeFrame: Months 0, 7, 13 and 24
measure: Number of Participants With Viral Sequences
timeFrame: Month 7 up to Month 24
Other outcomes:
Locations:
city: Lilongwe
country: Malawi
facility: UNC Lilongwe Project
city: Maputo
country: Mozambique
facility: Polana Caniço Health Research and Training Center (CISPOC)
city: Bloemfontein
country: South Africa
facility: Josha Research
city: Cape Town
country: South Africa
facility: Masiphumelele Research Centre
city: Dennilton
country: South Africa
facility: Ndlovu Elandsdoorn Site
city: Diepkloof
country: South Africa
facility: Perinatal HIV Research Unit, Chris Hani Baragwanath Hospital
city: Johannesburg
country: South Africa
facility: Perinatal HIV Research Unit, Chris Hani Baragwanath Hospital
city: Klerksdorp
country: South Africa
facility: The Aurum Institute Klerksdorp Clinical Research Centre
city: KwaZulu-Natal
country: South Africa
facility: Qhakaza Mbokodo Research Centre
city: KwaZulu-Natal
country: South Africa
facility: South African Medical Research Council Chatsworth Clinical Research Site
city: KwaZulu-Natal
country: South Africa
facility: Centre for the AIDS Programme of Research in South Africa
city: KwaZulu-Natal
country: South Africa
facility: South African Medical Research Council Tongaat Clinical Research Site
city: Mamelodi East
country: South Africa
facility: Stanza Clinical Research Centre : Mamelodi
city: Mthatha
country: South Africa
facility: Nelson Mandela Academic Clinical Research Unit 'NeMACRU'
city: Pretoria
country: South Africa
facility: MeCRU Clinical Research Unit
city: Rustenburg
country: South Africa
facility: The Aurum Institute Rustenburg Clinical Research Site
city: Soshanguve
country: South Africa
facility: Setshaba Research Centre
city: Tembisa
country: South Africa
facility: The Aurum Institute: Tembisa - Clinic 4
city: Lusaka
country: Zambia
facility: Centre for Infectious Disease Research in Zambia (CIDRZ)
city: Lusaka
country: Zambia
facility: Center for Family Health Research in Zambia (CFHRZ)
city: Ndola
country: Zambia
facility: Center for Family Health Research in Zambia (CFHRZ)
city: Chitungwiza
country: Zimbabwe
facility: St Mary's Clinic
city: Harare - Seke South
country: Zimbabwe
facility: University of Zimbabwe-UCSF
Study officials:
affiliation: Janssen Vaccines & Prevention B.V.
name: Janssen Vaccines & Prevention B.V. Clinical Trial
role: STUDY_DIRECTOR
References:
citation: 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.