NCT04364035

Safety, Tolerability and Immunogenicity of MVA.HTI and ChAdOx1.HTI With Vesatolimod in HIV-1 Positive Patients

A Phase IIa Randomised, Double-blind, Placebo-controlled Study of HIV-1 Vaccines MVA.HTI and ChAdOx1.HTI With TLR7 Agonist Vesatolimod (GS-9620) in Early Treated HIV-1 Infection

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 50 (actual)
• Sponsor: Aelix Therapeutics · Industry
• Sex: All
• Age: 18 Years – 60 Years
• Healthy volunteers: Not accepted

Summary

AELIX-003 study aims to investigate the safety, tolerability, immunogenicity and efficacy of a regimen containing AELIX Therapeutics' HTI T-cell vaccines and Gilead´s Toll-Like Receptor 7 (TLR7) agonist vesatolimod in HIV-infected individuals on antiretroviral therapy. Study that will be conducted in 57 participants who have started antiretroviral therapy during early HIV infection, enrolled at various clinical trial sites in Spain. All participants will be on antiretroviral therapy upon starting the study, with their HIV viral loads \<50 copies/mL. Following exposure to the vaccine/vesatolimod, all participants, under careful monitoring, will temporarily stop their antiretroviral drugs to determine if the intervention is effective in keeping their HIV levels under control.

Detailed description

Study will evaluate safety of the investigational drugs ChAdOx1.HTI and MVA.HTI (referenced collectively as CCMM) with vesatolimod (also known as GS-9620) in participants with early treated HIV-1 infection. The current study will also investigate the immunogenicity of CCMM + vesatolimod treatment and the impact of CCMM + vesatolimod treatment on viral rebound and viral control following an analytical treatment interruption (ATI) in participants with early treated HIV-1 infection. HIVACAT T cell immunogen (HTI) is a novel T cell immunogen covering the most vulnerable regions of HIV. The encoding DNA sequence that has been inserted in various vaccine vectors, including viral and non-viral vectors Administration of the HTI immunogen is implemented through a heterologous prime-boost approach that includes 2 vaccine components. The aim of the sequential administration of the therapeutic vaccines is to achieve a so-called "functional cure," in which HIV-infected participants can control viral replication in the absence of ART. In this double blind, randomised, safety and tolerability study (AELIX-003), the HTI immunogen will be administered in a prime-boost regimen consisting of vaccinations with ChAdOx1.HTI (prime) and MVA.HTI (boost). The treatment regimen in this study will also include a toll-like receptor 7 (TLR7) agonist, GS-9620, which is supported by a recent non clinical study where sequential administration of vaccines and a TLR7 agonist (GS-986, an analogue of vesatolimod) demonstrated efficacy in simian immunodeficiency virus (SIV)-infected rhesus monkeys on ART. HTI is currently being tested in the Phase I, double blind, placebo controlled clinical study AELIX-002 through a heterologous prime-boost vaccination employing 3 products expressing the HTI antigen, DNA.HTI and MVA.HTI and ChAdOx.HTI. The available clinical data from AELIX-002 do not suggest a risk for serious adverse events (SAEs) from the products alone, used sequentially, or from the immunogen itself. The study will screen HIV-1 infected participants who have initiated ART within 180 days (6 months) of the estimated date of HIV-1 acquisition and who have achieved virological suppression for at least 1 year prior entering AELIX-003. Participants who provide informed consent and meet study entry criteria will be randomised into 1 of 2 parallel treatment groups. The study will be conducted in 3 periods: Period 1 will last 48 weeks during which participants will receive blinded IMPs and will continue their ART regimen; Period 2 will last up to 24 weeks during which participants will discontinue their ART regimen; and Period 3 will last 12 weeks during which participants will be monitored following the restart of their ART.

Conditions

• HIV/AIDS

Interventions

Type	Name	Description
BIOLOGICAL	ChAdOx1.HTI	ChAdOx1.HTI at week 0 and week 12; Vaccine delivered as one 0. 5 mL IM injection
BIOLOGICAL	MVA.HTI	MVA.HTI at week 24 and week 36; Vaccine delivered as one 0. 5 mL IM injection
DRUG	GS-9620	GS-9620 at week 26,28,30,32,34,38,40,42,44 and 46 Unit-dose tablet, delivered as two 3-mg tablets
BIOLOGICAL	Placebo	Saline placebo delivered as one 0. 5 mL IM injection
DRUG	Placebo Oral Tablet	Unit-dose placebo tablet delivered as two 3-mg placebo tablets

Timeline

• Start date: 2020-02-20
• Primary completion: 2022-10-03
• Completion: 2022-12-16
• First posted: 2020-04-27
• Last updated: 2023-07-27

Locations

9 sites across 1 country: Spain

Regulatory

• FDA-regulated drug study