NCT03606213

Therapeutic Vaccination in Treated HIV Disease

Safety, Immunogenicty and Anti-Reservoir Activity of an Electroporation-Administered HIV DNA Vaccine Encoding GAG, POL and ENV Proteins With IL-12 Plasmid in HIV-Infected Adults on Antriretroviral Therapy.

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 56 (actual)
• Sponsor: Steven Deeks · Academic / Other
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Not accepted

Summary

The central premise of our program is that durable control of HIV in the absence of antiretroviral therapy ("remission") will require the generation of de novo potent and sustained HIV-specific CD8+ cell responses that target evolutionarily conserved epitopes. Our program is inspired by the recent success of VGX-3100 (Inovio), a DNA therapeutic vaccine for HPV that leads to histopathologic regression of pre-malignant lesions in people and is associated with a potent, sustained boost to HPV-specific CD8+ T cell populations. A closely related multi-clade gag/pol/env DNA vaccine administered with an IL-12 DNA plasmid (PENNVAX, Inovio) has been studied for HIV prevention and is known to be both safe and highly immunogenic. In a randomized placebo-controlled study we will compare the immunogenicity and anti-reservoir activities of gag/pol DNA versus gag/pol/env DNA (both administered with IL-12). We will determine for the first time in established HIV disease whether presence of env in a DNA vaccine blunts T cell responses to more conserved Gag-specific and Pol-specific epitopes. We will also determine if Env-specific responses (which will presumably be mediated by antibodies and antibody-dependent cellular cytotoxicity, or ADCC) have a measurable effect on reservoir.

Conditions

• HIV-1-infection

Interventions

Type	Name	Description
BIOLOGICAL	PENNVAX-GP	PENNVAX®-GP is a circular, double stranded, deoxyribonucleic acid consisting of expression plasmids that encode synthetic HIV-1 multiclade consensus Gag, Pol and Env proteins.
BIOLOGICAL	INO-6145	INO-6145 is a circular, double stranded, deoxyribonucleic acid consisting of expression plasmids that encode synthetic HIV-1 multiclade consensus Gag and Pol proteins.
BIOLOGICAL	INO-9012	The IL-12 DNA adjuvant (INO-9012) consists of a single plasmid containing a dual promoter system for expression of both the IL-12 p35 and p40 genes necessary for production of the active heterodimeric (p70) IL-12 protein.
DEVICE	CELLECTRA® 2000	Electroporation (EP) is a technology in which an electrical field is applied to increase the permeability of cell membranes and thereby enhance the uptake of drugs, vaccines, or other agents into target cells. This technology has been used in the last decade in both therapeutics and vaccinations. EP is currently being used to deliver cancer vaccines and therapeutics as well as in gene therapy. The expression levels are increased by as much as 3 orders of magnitude over plasmid injection alone.

Timeline

• Start date: 2018-08-01
• Primary completion: 2021-05-17
• Completion: 2021-05-17
• First posted: 2018-07-30
• Last updated: 2023-05-31
• Results posted: 2023-05-31

Locations

2 sites across 1 country: United States

Regulatory

• FDA-regulated drug study