Phase I, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability, and Immunogenicity of an Ad26.Mos4.HIV and CH505 TF chTrimer (Env) Combination to Mimic Acute HIV Viral Replication Kinetics in Healthy Adults

This is a Phase I, randomized, double-blind, placebo-controlled clinical study to define the safety and immunogenicity resulting from a rapid dose-escalating vaccination schedule as compared to that of a co-administered, dose-consistent vaccination schedule. Participants randomized to receive vaccines will get either dose-consistent injections of CH505 TF chTrimer+ALFQ co-administered with Ad26.Mos4.HIV or rapid, dose-escalating injections of CH505 TF chTrimer+ALFQ with an Ad26.Mos4.HIV prime, followed by dose-consistent injection of CH505 TF chTrimer+ALFQ co-administered with Ad26.Mos4.HIV

Start Date01 Jan 2024

Sponsor / Collaborator

U S Army Medical Research & Development Command

[+6]

NCT05769569 / WithdrawnPhase 1IIT

Safety and Efficacy of Broadly Neutralizing Antibodies Followed by Innate Immune Stimulation and Therapeutic Vaccination for the Induction of HIV Remission

This is a phase I, randomized, open-label trial to investigate the safety of VRC07-523LS, PGDM1400LS and N-803 in combination with Ad26.Mos4.HIV, MVA-Bavarian Nordic (BN)-HIV and A244d11gp120/ALFQ vaccination, and the impact on time to sustained viral rebound of ≥1000 copies/mL for 4 consecutive weeks during analytic treatment interruption (ATI) in people living with human immunodeficiency virus-1 (HIV-1, PLWH) who initiated antiretroviral therapy (ART) during acute HIV-1 infection (AHI).

Start Date01 Sep 2023

Sponsor / Collaborator

The Henry M. Jackson Foundation

[+1]

NCT04983030 / Active, not recruitingPhase 1/2IIT

A Safety, Immunogenicity and Efficacy Phase 1/2a Study of a Heterologous Ad26.Mos4.HIV, MVA-BN-HIV Vaccine Regimen Plus Broadly Neutralizing Antibodies PGT121, PGDM1400, and VRC07-523LS in HIV-1-Infected Adults on Suppressive ART

A multicenter, randomized, parallel-group, placebo-controlled, double-blind, Phase 1/2a clinical study to investigate the safety, tolerability, immunogenicity and exploratory efficacy of a vaccine regimen consisting of an Ad26.Mos4.HIV prime and a boost with Modified Vaccinia Ankara (MVA)-BN-HIV in combination with broadly neutralizing antibodies (bNAb) PGT121, PGDM1400, and VRC07-523LS in human immunodeficiency virus type 1 (HIV-1)-infected study participants on suppressive anti-retroviral therapy (ART).

Start Date01 Apr 2022

Sponsor / Collaborator

Beth Israel Deaconess Medical Center, Inc.

[+3]

100 Clinical Results associated with Ad26 Mos4 HIV tetravalent vaccine (Janssen Vaccines and Prevention B.V)

100 Translational Medicine associated with Ad26 Mos4 HIV tetravalent vaccine (Janssen Vaccines and Prevention B.V)

100 Patents (Medical) associated with Ad26 Mos4 HIV tetravalent vaccine (Janssen Vaccines and Prevention B.V)

Literatures (Medical) associated with Ad26 Mos4 HIV tetravalent vaccine (Janssen Vaccines and Prevention B.V)

01 Nov 2024·The Lancet Infectious Diseases

Mosaic HIV-1 vaccine regimen in southern African women (Imbokodo/HVTN 705/HPX2008): a randomised, double-blind, placebo-controlled, phase 2b trial

Article

Author: Juraska, Michal ; McElrath, M Juliana ; Hural, John ; Luedtke, Alex ; Mann, Philipp ; Tapley, Asa ; Swann, Edith ; Pau, Maria G ; Takalani, Azwidihwi N ; Mngadi, Kathryn ; van Duijn, Janine ; Van Hoof, Johan ; Lavreys, Ludo ; Kublin, James G ; Schuitemaker, Hanneke ; Gray, Glenda E ; Barouch, Dan H ; Buchbinder, Susan ; Willems, Wouter ; Gilbert, Peter B ; Hyrien, Ollivier ; Nijs, Steven ; Tomaras, Georgia D ; Stieh, Daniel J ; Corey, Lawrence ; Odhiambo, Jackline A ; Tomaka, Frank

BACKGROUNDHIV type 1 (HIV-1) remains a global health concern, with the greatest burden in sub-Saharan Africa. Despite 40 years of research, no vaccine candidate has shown durable and protective efficacy against HIV-1 acquisition. Although pre-exposure prophylaxis in groups with high vulnerability can be very effective, barriers to its use, such as perceived low acquisition risk, fear of stigma, and concerns about side-effects, remain. Thus, a population-based approach, such as an HIV-1 vaccine, is needed. The current study aimed to evaluate the efficacy and safety of a heterologous HIV-1 vaccine regimen, consisting of a tetravalent mosaic adenovirus 26-based vaccine (Ad26.Mos4.HIV) and aluminium phosphate-adjuvanted clade C glycoprotein (gp) 140, in young women at risk of acquiring HIV-1 in southern Africa.METHODSThis randomised, double-blind, phase 2b study enrolled sexually active women without HIV-1 or HIV-2 aged 18-35 years at 23 clinical research sites in Malawi, Mozambique, South Africa, Zambia, and Zimbabwe. Participants were centrally randomly assigned (1:1) to receive intramuscular injections of vaccine or saline placebo in stratified permuted blocks via an interactive web response system. Study participants, study site personnel (except those with primary responsibility for study vaccine preparation and dispensing), and investigators were masked to treatment group allocation. The vaccine regimen consisted of Ad26.Mos4.HIV administered at months 0 and 3 followed by Ad26.Mos4.HIV administered concurrently with aluminium phosphate-adjuvanted clade C gp140 at months 6 and 12. The primary efficacy outcome was vaccine efficacy in preventing laboratory-confirmed HIV-1 acquisition diagnosed between visits at month 7 and month 24 after the first vaccination (VE[7-24]) in the per-protocol population, which included participants who had not acquired HIV-1 4 weeks after the third vaccination, received all planned vaccinations at the first three vaccination visits within the protocol-specified windows, and had no major protocol deviations that could affect vaccine efficacy. Primary safety outcomes were assessed in randomly assigned participants who received one study injection or more based on the actual injection received. The primary safety endpoints were the incidences of unsolicited adverse events (AEs), solicited local and systemic AEs, serious AEs, AEs of special interest, and AEs leading to discontinuation of vaccination. This trial is registered with ClinicalTrials.gov, NCT03060629, and is complete.FINDINGSBetween Nov 3, 2017, and June 30, 2019, 2654 women were randomly assigned, of whom 2636 women (median age of 23 years [IQR 20-25]) were enrolled and received at least one study injection (1313 assigned vaccine, 1323 placebo; 1317 received vaccine, 1319 placebo). Analysis of the primary efficacy outcome in the per-protocol cohort included 1080 women in the vaccine group and 1108 women in the placebo group; the incidence of HIV-1 acquisition per 100 person-years over months 7-24 after the first vaccination was 3·38 (95% CI 2·54-4·41) in the vaccine group and 3·94 (3·04-5·03) in the placebo group, with an estimated VE(7-24) of 14·10% (95% CI -22·00 to 39·51; p=0·40). There were no serious unsolicited AEs, AEs of special interest, or deaths related to the study vaccine. In the vaccine group, 663 (50·3%) of 1317 participants had grade 1 or 2 solicited local AEs and ten (0·8%) of 1317 participants had grade 3 or 4 solicited local AEs. In the placebo group, 305 (23·1%) of 1319 participants had grade 1 or 2 solicited local AEs and three (0·2%) of 1319 participants had grade 3 or 4 solicited local AEs. 863 (65·5%) of 1317 participants in the vaccine group had grade 1 or 2 solicited systemic AEs and 34 (2·6%) of 1317 participants had grade 3 or 4 solicited systemic AEs. 763 (57·8%) of 1319 participants in the placebo group had grade 1 or 2 solicited systemic AEs and 20 (1·5%) of 1319 participants had grade 3 or 4 solicited systemic AEs. Overall, three (0·2%) of 1317 participants in the vaccine group and three (0·2%) of 1319 participants in the placebo group discontinued vaccination due to an unsolicited AE, and three (0·2%) of 1317 participants in the vaccine group and one (0·1%) of 1319 participants in the placebo group discontinued vaccination due to a solicited AE.INTERPRETATIONThe heterologous Ad26.Mos4.HIV and clade C gp140 vaccine regimen was safe and well tolerated but did not show efficacy in preventing HIV-1 acquisition in a population of young women in southern Africa at risk of HIV-1.FUNDINGDivision of AIDS at the National Institute of Allergy and Infectious Diseases through the HIV Vaccine Trials Network, Bill & Melinda Gates Foundation, Janssen Vaccines & Prevention, US Army Medical Materiel Development Activity, and Ragon Institute.

01 Nov 2020·Archives of VirologyQ4 · MEDICINE

Review of preventative HIV vaccine clinical trials in South Africa

Q4 · MEDICINE

Review

Author: Lazarus, Erica M ; Bekker, Linda-Gail ; Garrett, Nigel ; Gray, Glenda E ; Laher, Fatima

AbstractNew HIV infections continue relentlessly in southern Africa, demonstrating the need for a vaccine to prevent HIV subtype C. In South Africa, the country with the highest number of new infections annually, HIV vaccine research has been ongoing since 2003 with collaborative public-private-philanthropic partnerships. So far, 21 clinical trials have been conducted in South Africa, investigating seven viral vectors, three DNA plasmids, four envelope proteins, five adjuvants and three monoclonal antibodies. Active vaccine candidates have spanned subtypes A, B, C, E and multi-subtype mosaic sequences. All were well tolerated. Four concepts were investigated for efficacy: rAd5-gag/pol/nef showed increased HIV acquisition in males, subtype C ALVAC/gp120/MF59 showed no preventative efficacy, and the trials for the VRC01 monoclonal antibody and Ad26.Mos4.HIV/subtype C gp140/ aluminum phosphate are ongoing. Future trials are planned with DNA/viral vector plus protein combinations in concert with pre-exposure prophylaxis, and sequential immunization studies with transmitted/founder HIV envelope to induce broadly neutralizing antibodies. Finally, passive immunization trials are underway to build on the experience with VRC01, including single and combination antibody trials with an antibody derived from a subtype-C-infected South African donor. Future consideration should be given to the evaluation of novel strategies, for example, inactivated-whole-virus vaccines.

01 Oct 2020·The Lancet HIVQ1 · MEDICINE

Safety and immunogenicity of two heterologous HIV vaccine regimens in healthy, HIV-uninfected adults (TRAVERSE): a randomised, parallel-group, placebo-controlled, double-blind, phase 1/2a study

Q1 · MEDICINE

Article

Author: Lauren Peter ; Colleen Kelly ; Nadine Rouphael ; Philipp Mann ; Steven Nijs ; Michal Sarnecki ; James G Kublin ; Julie A. Ake ; Georgia D Tomaras ; Michael Keefer ; Magda Sobieszczyk ; Dan H Barouch ; Dimitri Goedhart ; Merlin L. Robb ; Johannes P Langedijk ; Kristen W. Cohen ; Srilatha Edupuganti ; Lawrence Corey ; Karen Buleza ; Frank Tomaka ; Daniel J Stieh ; Maria G Pau ; Galit Alter ; Etienne Karita ; Lorenz Scheppler ; Hong Van Tieu ; Susan Buchbinder ; Zelda Euler ; Hanneke Schuitemaker ; Paul Goepfert ; Guido Ferrari ; M Juliana McElrath ; Trevor A. Crowell ; Frank Wegmann ; Joseph Nkolola ; Ken Mayer ; David Montefiori ; Katleen Callewaert ; Ian Frank ; Stephen R Walsh ; Lindsey R Baden

BACKGROUNDBioinformatically designed mosaic antigens increase the breadth of HIV vaccine-elicited immunity. This study compared the safety, tolerability, and immunogenicity of a newly developed, tetravalent Ad26 vaccine with the previously tested trivalent formulation.METHODSThis randomised, parallel-group, placebo-controlled, double-blind, phase 1/2a study (TRAVERSE) was done at 11 centres in the USA and one centre in Rwanda. Eligible participants were adults aged 18 to 50 years, who were HIV-uninfected, healthy at screening based on their medical history and a physical examination including laboratory assessment and vital sign measurements, and at low risk of HIV infection in the opinion of study staff, who applied a uniform definition of low-risk guidelines that was aligned across sites. Enrolled participants were randomly assigned at a 2:1 ratio to tetravalent and trivalent groups. Participants in tetravalent and trivalent groups were then further randomly assigned at a 5:1 ratio to adenovirus 26 (Ad26)-vectored vaccine and placebo subgroups. Randomisation was stratified by region (USA and Rwanda) and based on a computer-generated schedule using randomly permuted blocks prepared under the sponsor's supervision. We masked participants and investigators to treatment allocation throughout the study. On day 0, participants received a first injection of tetravalent vaccine (Ad26.Mos4.HIV or placebo) or trivalent vaccine (Ad26.Mos.HIV or placebo), and those injections were repeated 12 weeks later. At week 24, vaccine groups received a third dose of tetravalent or trivalent together with clade C gp140, and this was repeated at week 48, with placebos again administered to the placebo group. All study vaccines and placebo were administered by intramuscular injection in the deltoid muscle. We assessed adverse events in all participants who received at least one study injection (full analysis set) and Env-specific binding antibodies in all participants who received at least the first three vaccinations according to the protocol-specified vaccination schedule, had at least one measured post-dose blood sample collected, and were not diagnosed with HIV during the study (per-protocol set). This study is registered with Clinicaltrials.gov, NCT02788045.FINDINGSOf 201 participants who were enrolled and randomly assigned, 198 received the first vaccination: 110 were in the tetravalent group, 55 in the trivalent group, and 33 in the placebo group. Overall, 185 (93%) completed two scheduled vaccinations per protocol, 180 (91%) completed three, and 164 (83%) completed four. Solicited, self-limiting local, systemic reactogenicity and unsolicited adverse events were similar in vaccine groups and higher than in placebo groups. All participants in the per-protocol set developed clade C Env binding antibodies after the second vaccination, with higher total IgG titres after the tetravalent vaccine than after the trivalent vaccine (10 413 EU/mL, 95% CI 7284-14 886 in the tetravalent group compared with 5494 EU/mL, 3759-8029 in the trivalent group). Titres further increased after the third and fourth vaccinations, persisting at least through week 72. Other immune responses were also higher with the tetravalent vaccine, including the magnitude and breadth of binding antibodies against a cross-clade panel of Env antigens, and the magnitude of IFNγ ELISPOT responses (median 521 SFU/10⁶ peripheral blood mononuclear cells [PBMCs] in the tetravalent group and median 282 SFU/10⁶ PBMCs in the trivalent group after the fourth vaccination) and Env-specific CD4+ T-cell response rates after the third and fourth vaccinations. No interference by pre-existing Ad26 immunity was identified.INTERPRETATIONThe tetravalent vaccine regimen was generally safe, well-tolerated, and found to elicit higher immune responses than the trivalent regimen. Regimens that use this tetravalent vaccine component are being advanced into field trials to assess efficacy against HIV-1 infection.FUNDINGNational Institutes of Health, Henry M Jackson Foundation for Advancement of Military Medicine and the US Department of Defense, Ragon Institute of MGH, MIT, & Harvard, Bill & Melinda Gates Foundation, and Janssen Vaccines & Prevention.

100 Deals associated with Ad26 Mos4 HIV tetravalent vaccine (Janssen Vaccines and Prevention B.V)

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10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
HIV Infections	Discovery	PE	Janssen Vaccines & Prevention BV	31 Oct 2019
HIV Infections	Discovery	AR	Janssen Vaccines & Prevention BV	31 Oct 2019
HIV Infections	Discovery	PL	Janssen Vaccines & Prevention BV	31 Oct 2019
HIV Infections	Discovery	US	Janssen Vaccines & Prevention BV	31 Oct 2019
HIV Infections	Discovery	ES	Janssen Vaccines & Prevention BV	31 Oct 2019
HIV Infections	Discovery	IT	Janssen Vaccines & Prevention BV	31 Oct 2019
HIV Infections	Discovery	MX	Janssen Vaccines & Prevention BV	31 Oct 2019
HIV Infections	Discovery	PR	Janssen Vaccines & Prevention BV	31 Oct 2019
HIV Infections	Discovery	BR	Janssen Vaccines & Prevention BV	31 Oct 2019

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02788045 (TRAVERSE, CTgov)	Phase 1/2	-	201	Ad26.Mos4.HIV Vaccine (Tetravalent Ad26.Mos4.HIV Vaccine)	ecvimqmgld(svjnepbszo) = zaihswfien voryhenqhi (vliatxlnzn, vkkddxgkre - dktslxrtzm) View more	-	09 Jun 2023
				Ad26.Mos.HIV Vaccine (Trivalent Ad26.Mos.HIV Vaccine)	ecvimqmgld(svjnepbszo) = zmlkcdrokj voryhenqhi (vliatxlnzn, bmqypshteq - tbkcnerixk) View more
NCT03060629 (CTgov)	Phase 2	HIV Infections	2,636	Ad26.Mos.HIV Vaccine (Group 1: Ad26.Mos.HIV Vaccine)	ogybbcnwur(ywdaigshwt) = bgvgcnwbsb viwloqwqtv (xpnzloycou, hoqhuopnnl - ecqxblteov) View more	-	18 Apr 2023
				Placebo+Ad26.Mos4.HIV (Group 2: Placebo)	ogybbcnwur(ywdaigshwt) = efwffzlzfa viwloqwqtv (xpnzloycou, puggrxbyle - nyqomddblu) View more

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Ad26 Mos4 HIV tetravalent vaccine (Janssen Vaccines and Prevention B.V)

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