The Safety and Immunogenicity of the DNA-GTU Vaccine Administered to HIV-infected Patients on ART vs Placebo — CUTHIVTHER001  

HIV Clinical Trial

Official title: A Randomized Phase I/II Study to Assess the Safety and Immunogenicity of the DNA-GTU Vaccine Administered by Two Novel Routes Compared to Placebo in HIV-infected Patients on Antiretroviral Therapy

Status Completed

Clinical Trial Summary

CUT*HIVTHER 001 is a randomised placebo-controlled Phase I/II study aimed at exploring the safety and immunogenicity of two different modes of delivery of a GTU® DNA plasmid vaccine (GTU®-multiHIV B clade) in HIV infected volunteers on antiretroviral therapy (ART):

• Transcutaneous (TC) delivery to enhance intramuscular delivery and

• Electroporation (EP) enhanced intramuscular delivery Participants will be randomised 1:1:1 to TC:EP:saline for the purposes of analysis. Half the saline group will receive TC saline and half will receive EP saline.

30 HIV infected male and female volunteers aged 18-45 years, who have been on ART for at least 6 months with 2 or more HIV plasma viral load measurements < 50 copies HIV RNA/ml prior to enrolment.

The investigational HIV-1 vaccine GTU®-MultiHIV B clade encodes for a MultiHIV antigen which is a synthetic fusion protein consisting of full-length polypeptides of Rev, Nef, Tat, p17 and p24 and containing more than 20 Th and CTL epitopes of protease, reverse transcriptase (RT) and gp160 regions of the HAN2 HIV-1 B clade.

Vaccine is provided in sealed vials at 2mg/ml, and a single 1ml IM injection of 2mg GTU®-MultiHIV DNA IM (into the thigh) is required to deliver a 2mg dose. Individuals in Group 2 will receive a further 0.4mg GTU®-MultiHIV DNA in 0.2ml administered by TC, a novel needle-free method of vaccine delivery.

Clinical Trial Description

The investigators are exploring combination regimens with the overall aims of (i) optimising immune responses and (ii) developing safe and well tolerated strategies which will favour the development of T-cell responses that may enhance anti-HIV HIV therapy with the forward looking goal of working towards functional eradication of infection. The investigator proposes to combine the previously used IM and TC methods because preclinical data suggest that the combination of methods will favour the development of CD8 T cell responses. All groups will receive 6.0mg of the vaccine IM given in 3 doses over 12 weeks. Group 1 will receive the 6.0mg IM with electroporation (EP) and Group 2 will receive the 6.0mg IM without EP but together with an additional 1.2mg vaccine TC. The primary immunogenicity endpoint will be to determine whether either intervention group augments the cellular responses to vaccine specific peptides in relation to baseline. It is anticipated that none of subjects receiving saline placebo would have an increase in vaccine specific responses relative to those at baseline. Therefore if the differences between the active groups and saline placebo are sufficiently large, for example 80% responders in a GTU®-MultiHIV DNA active group, <10% in the control group, this would be significant.

Should the regimes prove safe, acceptable and induce significant immunogenicity then the intention is to move one or both regimes into a larger study powered to determine their potential long-term impact on therapy when used in combination with conventional ARV regimens. Proof of concept that DNA vaccination can induce de novo HIV specific responses that are associated with control of viral replication, would justify further investigation of their use in immunotherapies combined with ART intensification and/or anti-latency drugs. ;

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• HIV

• NCT number: NCT02457689
• Study type: Interventional
• Source: Imperial College London
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: July 2015
• Completion date: July 2016