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

NCT04364035 | Completed Phase 2 DMC FDA Drug

• 1 other identifier: AELIX-003
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 9

Brief 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.

Conditions

HIV/AIDS

Keywords

HIV infection; Therapeutic Vaccines; HTI; TLR7

Outcome Measures

Primary Outcomes (3)

• Proportion of participants developing solicited Grade 3 or 4 local reactions

  Proportion of participants developing solicited Grade 3 or 4 local reactions in the 7-day period following administration of IMPs during Period 1

  During Period 1 (Weeks 0 to 48)

• Proportion of participants developing solicited Grade 3 or 4 systemic reactions

  Proportion of participants developing solicited Grade 3 or 4 systemic reactions in the 7-day period following administration of IMPs during Period 1

  During Period 1 (Weeks 0 to 48)

• Proportion of participants developing treatment-emergent SAEs

  Proportion of participants developing treatment-emergent SAEs during Period 1

  During Period 1 (Weeks 0 to 48)

Secondary Outcomes (6)

• Proportion of participants who achieve virologic suppression after resumption of ART

  After period 1(Week 48 to week 84)

• Proportion of participants developing treatment-emergent adverse events and SAEs (TEAEs)

  After period 1(Week 48 to week 84)

• Proportion of participants with viral load <50 copies/mL/ <2000 copies/mL at 12 and 24 weeks after the start of ATI

  Week 48 to week 72

• Proportion of participants that remain off ART at 12 and 24 weeks after the start of ATI

  Week 48 to week 72

• Breadth of total vaccine-induced HIV 1-specific responses

  Period1 (week 0 to 48)

Other Outcomes (7)

• Evaluate the pharmacodynamic (PD) in Serum /plasma cytokines of GS-9620

  week 26- week 46

• Evaluate the pharmacodynamic (PD) in gene expression of GS-9620

  week 26- week 46

• Evaluate the pharmacodynamic (PD) effects of GS-9620

  week 26- week 46

Study Arms (2)

CCMM+GS-9620

EXPERIMENTAL

ChAdOx1.HTI 2 doses, MVA.HTI 2 doses, GS-9620 10 doses.

Biological: ChAdOx1.HTI; Biological: MVA.HTI; Drug: GS-9620

PLACEBO

PLACEBO COMPARATOR

ChAdOx1.HTI placebo 2 doses, MVA.HTI placebo 2 doses, GS-9620, placebo 10 doses.

Biological: Placebo; Drug: Placebo Oral Tablet

Interventions

ChAdOx1.HTI BIOLOGICAL

ChAdOx1.HTI at week 0 and week 12; Vaccine delivered as one 0. 5 mL IM injection

CCMM+GS-9620

MVA.HTI BIOLOGICAL

MVA.HTI at week 24 and week 36; Vaccine delivered as one 0. 5 mL IM injection

CCMM+GS-9620

GS-9620 DRUG

GS-9620 at week 26,28,30,32,34,38,40,42,44 and 46 Unit-dose tablet, delivered as two 3-mg tablets

Also known as: Vesatolimod

CCMM+GS-9620

Placebo BIOLOGICAL

Saline placebo delivered as one 0. 5 mL IM injection

PLACEBO

Placebo Oral Tablet DRUG

Unit-dose placebo tablet delivered as two 3-mg placebo tablets

Also known as: N/H

PLACEBO

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Understands the study information provided and is capable of giving written informed consent, in the opinion of the investigator or designee.
• Has confirmed HIV-1 infection.
• Has received ART that was initiated within 6 months of the estimated date of HIV-1 acquisition. The ART regimen is required to have included ≥3 antiretroviral drugs at the time of treatment initiation and is required to include ≥3 antiretroviral drugs at screening, but temporary use of a 2-drug ART regimen during the time between ART initiation and the screening visit is permitted
• Has plasma HIV-1 RNA levels \<50 copies/mL at the screening visit and has been virologically suppressed, defined as pVL \<50 copies/mL, for at least 1 year before screening; isolated blips allowed
• Has documented stable CD4 counts ≥450 cells/mm3 for the 6 months before screening and at the screening visit.
• Has nadir CD4 count ≥200 cells/mm3 since human immunodeficiency virus (HIV) diagnosis; isolated lower counts at the moment of acute HIV-1 infection will be allowed only if appropriate immune recovery was followed after ART initiation
• Is ≥18 and \<61 years of age on the day of screening.
• Is willing to comply with all study procedures, including the ATI, collection of blood samples per the protocol and adherence to the ART regimen, and is available for the planned duration of the study.
• If heterosexually active female and of childbearing potential, must be using highly effective methods of contraception from 14 days before the first vaccination until 30 days after the end of the study (or 40 days after the last dose of vesatolimod, whichever is later); all female volunteers must be willing to undergo urine pregnancy testing at the time points specified in the schedules of events.
• Female participants who use hormonal contraceptive as one of their birth control methods must have used the same method for at least 3 months before the first vaccination.
• Female participants who have stopped menstruating for ≥12 months but do not have documentation of ovarian hormonal failure must have a serum follicle stimulating hormone level at screening that is within the post menopausal range as provided in the Central Laboratory Manual.
• If heterosexually active male, must use condoms or practice sexual abstinence from the screening visit until 90 days after the end of the study (or 100 days after the last dose of vesatolimod, whichever is later). Female partners of male participants must be using highly effective methods of birth control from the screening visit until 90 days after the end of the study (or 100 days after the last dose of vesatolimod, whichever is later)

You may not qualify if:

• Is pregnant or lactating at the screening visit or at any time during the study or is planning on becoming pregnant over the duration of the study.
• If available, has genotypic data (e.g., HIV genotype data) that demonstrate the presence of clinically significant mutations that would prevent the construction of a viable ART regimen post-treatment interruption.
• Has reported multiple periods of suboptimal adherence to ART, defined as reported episodes of at least 3 days without ART that were unrelated to participation in an ATI clinical study.
• Has a history of past ART interruptions lasting longer than 2 weeks.
• Has participated in another interventional clinical study within 30 days before screening.
• Has any acquired immune deficiency syndrome-defining disease or progression of HIV related disease within 90 days of screening visit.
• Has a history of any moderate and/or severe autoimmune disease
• Has a history or clinical manifestations of any physical or psychiatric disorder that could impair the participant's ability to complete the study.
• Is taking HIV protease inhibitors (including low-dose ritonavir), cobicistat-containing regimens, elvitegravir, efavirenz, etravirine, or nevirapine. Participants on prohibited ART medications will be allowed to switch to an accepted treatment between screening and baseline.
• Is taking any other concomitant treatments non compatible with vesatolimod Participants on non-compatible medications at screening (e.g., atorvastatin, proton pump inhibitors) will be allowed to switch treatments; non compatible medications must be stopped at least 30 days prior to the first dose of vesatolimod.
• Has received approved vaccines within 2 weeks of study entry or has had a previous immunisation with any experimental immunogens within the previous 2 years.
• Will receive any vaccines within 4 weeks prior to, or 2 weeks after, any of the planned CCMM administrations or on a week when vesatolimod is administered.
• Has a history of anaphylaxis or a severe adverse reaction to vaccines.
• Has received blood products within 6 months of screening.
• Has received treatment for cancer or lymphoproliferative disease within 1 year of screening.

Sponsors & Collaborators

• Aelix Therapeutics: lead
• Gilead Sciences: collaborator

Study Sites (9)

IrsiCaixa AIDS Research Institute, Hospital Universitari Germans Trias i Pujol

Badalona, Barcelona, 08916, Spain

Location

Hospital Universitario de Bellvitge

L'Hospitalet de Llobregat, Barcelona, 08907, Spain

Location

Hospital de la Santa Creu i Sant Pau

Barcelona, 08025, Spain

Location

Hospital Clinic de Barcelona

Barcelona, 08036, Spain

Location

Hospital Universitario Vall d'Hebrón

Barcelona, 08935, Spain

Location

Hospital La Princesa

Madrid, 28006, Spain

Location

Hospital General Universitario Gregorio Marañón

Madrid, 28007, Spain

Location

Hospital Universitario Ramon y Cajal

Madrid, 28034, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome; HIV Infections

Interventions

vesatolimod

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Study Officials

• Jose R Arribas Lopez, Md, PhD

  Hospital Universitario La Paz

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: double Blind, Two or more parties are unaware of the interventional assignment
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: double-blind, placebo-controlled

Study Record Dates

• First Submitted: March 5, 2020
• First Posted: April 27, 2020
• Study Start: February 20, 2020
• Primary Completion: October 3, 2022
• Study Completion: December 16, 2022
• Last Updated: July 27, 2023

Record last verified: 2023-07

Locations

ES (9)