ChAdOx1.HTI / Aelix Therap - LARVOL DELTA

Safety, immunogenicity and effect on viral rebound of HTI vaccines combined with a TLR7 agonist in early-treated HIV-1 infection: a randomized, placebo-controlled phase 2a trial. (PubMed, Nat Commun) - P2a | "Building on results from the AELIX-002 trial with HIVACAT T-cell immunogen (HTI)-based vaccines, the AELIX-003 (NCT04364035) trial tested the safety of the combination of ChAdOx1.HTI (C) and MVA.HTI (M), with the TLR7 agonist vesatolimod (VES), in a double-blind, placebo-controlled, randomized clinical trial in 50 virally suppressed early-treated men with HIV-1 infection. Post hoc analysis confirmed a correlation between levels of HTI-specific T cells and prolonged time off antiretroviral therapy. The combination of HTI vaccines and VES was safe and elicited robust T-cell responses."

Clinical • Journal • P2a data • Fatigue • Human Immunodeficiency Virus • Infectious Disease • Influenza • Pain • Respiratory Diseases

A Phase I, Randomized, Double-Blind, Placebo-Controlled Safety, Tolerability and Immunogenicity Study of Candidate HIV-1 Vaccines ChAdOx1.HTI and MVA.HTI With Recombinant HIV-1 Envelope Protein ConM SOSIP.v7 gp140 Vaccine, Adjuvanted With MPLA Liposomes in ART-Suppressed HIV-1 Positive Individuals (clinicaltrials.gov) - P1 | N=30 | Completed | Sponsor: IrsiCaixa | Active, not recruiting ➔ Completed

Trial completion • Human Immunodeficiency Virus • Infectious Disease • CD4

A Phase I, Randomized, Double-Blind, Placebo-Controlled Safety, Tolerability and Immunogenicity Study of Candidate HIV-1 Vaccines ChAdOx1.HTI and MVA.HTI With Recombinant HIV-1 Envelope Protein ConM SOSIP.v7 gp140 Vaccine, Adjuvanted With MPLA Liposomes in ART-Suppressed HIV-1 Positive Individuals (clinicaltrials.gov) - P1 | N=30 | Active, not recruiting | Sponsor: IrsiCaixa | Trial completion date: Mar 2023 ➔ Dec 2023

Trial completion date • Human Immunodeficiency Virus • Infectious Disease • CD4

AELIX-003: Safety, Tolerability and Immunogenicity of MVA.HTI and ChAdOx1.HTI With Vesatolimod in HIV-1 Positive Patients (clinicaltrials.gov) - P2a | N=50 | Completed | Sponsor: Aelix Therapeutics | Active, not recruiting ➔ Completed | Trial primary completion date: Apr 2022 ➔ Oct 2022

Trial completion • Trial primary completion date • Human Immunodeficiency Virus • Infectious Disease • CD4

A PLACEBO-CONTROLLED RANDOMIZED TRIAL OF THE HTI IMMUNOGEN VACCINE AND VESATOLIMOD (CROI 2023) - P2a | "Backgrounds: In early-treated people with HIV (PWH), the HIV-specific T cell response induced by a combination of DNA.HTI (D), MVA.HTI (M) and ChAdOx1.HTI (C) vaccines was associated with longer time off antiretroviral therapy (ART) during analytical treatment interruption (ATI) (AELIX-002; Bailón L et al. In early-treated PWH, HTI vaccines and VES were safe and induced stronger HTI responses than the more complex AELIX-002 vaccine regimen. Mechanism of action and viral outcome correlate analyses are ongoing."

Clinical • Late-breaking abstract • Human Immunodeficiency Virus • Infectious Disease • CD4 • IL1R1

A Phase I, Randomized, Double-Blind, Placebo-Controlled Safety, Tolerability and Immunogenicity Study of Candidate HIV-1 Vaccines ChAdOx1.HTI and MVA.HTI With Recombinant HIV-1 Envelope Protein ConM SOSIP.v7 gp140 Vaccine, Adjuvanted With MPLA Liposomes in ART-Suppressed HIV-1 Positive Individuals (clinicaltrials.gov) - P1 | N=30 | Recruiting | Sponsor: IrsiCaixa | Active, not recruiting ➔ Recruiting

Enrollment open • Human Immunodeficiency Virus • Infectious Disease • CD4

A Phase I, Randomized, Double-Blind, Placebo-Controlled Safety, Tolerability and Immunogenicity Study of Candidate HIV-1 Vaccines ChAdOx1.HTI and MVA.HTI With Recombinant HIV-1 Envelope Protein ConM SOSIP.v7 gp140 Vaccine, Adjuvanted With MPLA Liposomes in ART-Suppressed HIV-1 Positive Individuals (clinicaltrials.gov) - P1 | N=30 | Active, not recruiting | Sponsor: IrsiCaixa | Recruiting ➔ Active, not recruiting

Enrollment closed • Human Immunodeficiency Virus • Infectious Disease • CD4

Safety, immunogenicity and effect on viral rebound of HTI vaccines in early treated HIV-1 infection: a randomized, placebo-controlled phase 1 trial. (PubMed, Nat Med) - P1 | "The AELIX-002 trial was a randomized, placebo-controlled trial to evaluate as a primary objective the safety of a combination of DNA.HTI (D), MVA.HTI (M) and ChAdOx1.HTI (C) vaccines in 45 early-antiretroviral (ART)-treated individuals (44 men, 1 woman; NCT03204617). Plasma viral load at the end of ATI and time off ART positively correlated with vaccine-induced HTI-specific T-cell responses at ART cessation. Despite limited efficacy of the vaccines in preventing viral rebound, their ability to elicit robust T-cell responses towards HTI may be beneficial in combination cure strategies, which are currently being tested in clinical trials."

Journal • P1 data • Human Immunodeficiency Virus • Immunology • Infectious Disease • CD4 • CD8

Safety and Immunogenicity of Candidate HIV Vaccines Given Sequentially (clinicaltrials.gov) - P1/2 | N=10 | Completed | Sponsor: University of Oxford | Active, not recruiting ➔ Completed

Trial completion • Human Immunodeficiency Virus • Infectious Disease

A Phase I, Randomized, Double-Blind, Placebo-Controlled Safety, Tolerability and Immunogenicity Study of Candidate HIV-1 Vaccines ChAdOx1.HTI and MVA.HTI With Recombinant HIV-1 Envelope Protein ConM SOSIP.v7 gp140 Vaccine, Adjuvanted With MPLA Liposomes in ART-Suppressed HIV-1 Positive Individuals (clinicaltrials.gov) - P1 | N=30 | Recruiting | Sponsor: IrsiCaixa | Not yet recruiting ➔ Recruiting

Enrollment open • Human Immunodeficiency Virus • Infectious Disease • CD4

Study to Assess the Safety and Durability of Viral Control Beyond 24 Weeks of Analytical Treatment Interruption After the Administration of Candidate HIV-1 Vaccines DNA.HTI, MVA.HTI and ChAdOx1.HTI or Placebo in Early Treated HIV-1 Positive Individuals (ATI Extension of AELIX-002 Study) (clinicaltrials.gov) - P1 | N=6 | Completed | Sponsor: Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia | Active, not recruiting ➔ Completed

Trial completion • Human Immunodeficiency Virus • Infectious Disease • CD4

Safety and Immunogenicity of Candidate HIV Vaccines Given Sequentially (clinicaltrials.gov) - P1/2 | N=10 | Active, not recruiting | Sponsor: University of Oxford | Recruiting ➔ Active, not recruiting

Enrollment closed • Human Immunodeficiency Virus • Infectious Disease • IFNG

A Phase I, Randomized, Double-Blind, Placebo-Controlled Safety, Tolerability and Immunogenicity Study of Candidate HIV-1 Vaccines ChAdOx1.HTI and MVA.HTI With Recombinant HIV-1 Envelope Protein ConM SOSIP.v7 gp140 Vaccine, Adjuvanted With MPLA Liposomes in ART-Suppressed HIV-1 Positive Individuals (clinicaltrials.gov) - P1; N=30; Not yet recruiting; Sponsor: IrsiCaixa

New P1 trial • Human Immunodeficiency Virus • Infectious Disease • CD4

Study to Assess the Safety and Durability of Viral Control Beyond 24 Weeks of Analytical Treatment Interruption After the Administration of Candidate HIV-1 Vaccines DNA.HTI, MVA.HTI and ChAdOx1.HTI or Placebo in Early Treated HIV-1 Positive Individuals (ATI Extension of AELIX-002 Study) (clinicaltrials.gov) - P1; N=6; Active, not recruiting; Sponsor: Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia; N=40 ➔ 6; Trial completion date: Jun 2022 ➔ Feb 2022; Trial primary completion date: Jun 2022 ➔ Aug 2021

Clinical • Enrollment change • Trial completion date • Trial primary completion date • Human Immunodeficiency Virus • Infectious Disease • CD4

AELIX-003: Safety, Tolerability and Immunogenicity of MVA.HTI and ChAdOx1.HTI With Vesatolimod in HIV-1 Positive Patients (clinicaltrials.gov) - P2a; N=57; Active, not recruiting; Sponsor: Aelix Therapeutics; Recruiting ➔ Active, not recruiting

Enrollment closed • Human Immunodeficiency Virus • Infectious Disease • CD4 • IFNG

Safety and Immunogenicity of Candidate HIV Vaccines Given Sequentially (clinicaltrials.gov) - P1/2; N=10; Recruiting; Sponsor: University of Oxford; Not yet recruiting ➔ Recruiting; Trial completion date: Oct 2021 ➔ Jun 2022; Initiation date: Mar 2021 ➔ Jun 2021; Trial primary completion date: Oct 2021 ➔ Jun 2022

Clinical • Enrollment open • Trial completion date • Trial initiation date • Trial primary completion date • Human Immunodeficiency Virus • Infectious Disease • IFNG

Safety and Immunogenicity Study of DNA.HTI, MVA.HTI and ChAdOx1.HTI in HIV-1-positive Patients (AELIX-002) (clinicaltrials.gov) - P1; N=45; Completed; Sponsor: Aelix Therapeutics; Active, not recruiting ➔ Completed

Trial completion • Human Immunodeficiency Virus • Infectious Disease • CD4

[VIRTUAL] A PLACEBO-CONTROLLED ATI TRIAL OF HTI VACCINES IN EARLY TREATED HIV INFECTION (CROI 2021) - P1, P2a | "Background: HTI is a novel HIV vaccine immunogen designed at redirecting cellular immune responses to HIV targets associated with viral control. The AELIX-002 trial (NCT03204617) was a randomized, singlecenter, placebo-controlled trial to evaluate the safety, immunogenicity and antiviral effect of DNA.HTI (D), MVA.HTI (M) and ChAdOx1.HTI (C) vaccines after discontinuation of ART in early-treated people living with HIV (PLWH)... HTI vaccines were safe and highly immunogenic in early-treated PLWH with a prolonged time off ART seen in vaccinees with non-beneficial HLA class I alleles. Time off ART positively correlated with vaccine-induced HTIspecific T cell responses at ATI start. Multivariate analysis for other correlates of response is ongoing."

Clinical • Late-breaking abstract • Human Immunodeficiency Virus • Infectious Disease • CD4

Safety and Immunogenicity of Candidate HIV Vaccines Given Sequentially (clinicaltrials.gov) - P1/2; N=10; Not yet recruiting; Sponsor: University of Oxford; Initiation date: Oct 2020 ➔ Mar 2021; Trial primary completion date: May 2021 ➔ Oct 2021

Clinical • Trial initiation date • Trial primary completion date • Human Immunodeficiency Virus • Infectious Disease

Study to Assess the Safety and Durability of Viral Control Beyond 24 Weeks of Analytical Treatment Interruption After the Administration of Candidate HIV-1 Vaccines DNA.HTI, MVA.HTI and ChAdOx1.HTI or Placebo in Early Treated HIV-1 Positive Individuals (ATI Extension of AELIX-002 Study) (clinicaltrials.gov) - P1; N=40; Active, not recruiting; Sponsor: Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed • Human Immunodeficiency Virus • Infectious Disease

Safety and Immunogenicity of Candidate HIV Vaccines Given Sequentially (clinicaltrials.gov) - P1/2; N=10; Not yet recruiting; Sponsor: University of Oxford

Clinical • New P1/2 trial • Human Immunodeficiency Virus • Infectious Disease

Safety and Immunogenicity Study of DNA.HTI, MVA.HTI and ChAdOx1.HTI in HIV-1-positive Patients (AELIX-002) (clinicaltrials.gov) - P1; N=45; Active, not recruiting; Sponsor: Aelix Therapeutics; Trial completion date: Sep 2020 ➔ Mar 2021; Trial primary completion date: Jan 2020 ➔ Jul 2020

Clinical • Trial completion date • Trial primary completion date • Human Immunodeficiency Virus • Infectious Disease

Study to Assess the Safety and Durability of Viral Control Beyond 24 Weeks of Analytical Treatment Interruption After the Administration of Candidate HIV-1 Vaccines DNA.HTI, MVA.HTI and ChAdOx1.HTI or Placebo in Early Treated HIV-1 Positive Individuals (ATI Extension of AELIX-002 Study) (clinicaltrials.gov) - P1; N=40; Recruiting; Sponsor: Fundacio Lluita Contra la SIDA; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Gene Therapies • Human Immunodeficiency Virus • Infectious Disease

Study to Assess the Safety and Durability of Viral Control Beyond 24 Weeks of Analytical Treatment Interruption After the Administration of Candidate HIV-1 Vaccines DNA.HTI, MVA.HTI and ChAdOx1.HTI or Placebo in Early Treated HIV-1 Positive Individuals (ATI Extension of AELIX-002 Study) (clinicaltrials.gov) - P1; N=40; Not yet recruiting; Sponsor: Fundacio Lluita Contra la SIDA

Clinical • New P1 trial • Gene Therapies • Genetic Disorders • Human Immunodeficiency Virus • Infectious Disease

AELIX-003: Safety, Tolerability and Immunogenicity of MVA.HTI and ChAdOx1.HTI With Vesatolimod in HIV-1 Positive Patients (clinicaltrials.gov) - P2a; N=57; Recruiting; Sponsor: Aelix Therapeutics

Clinical • New P2a trial • Gene Therapies • Genetic Disorders • Human Immunodeficiency Virus • Infectious Disease