Clinical trial NCT03606213: Therapeutic Vaccination in Treated HIV Disease
Official title: 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: HIV-1-infection
Keywords: HIV Vaccine
Electroporation
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
Collaborators: name: National Institute of Allergy and Infectious Diseases (NIAID)
name: University of California, Los Angeles
name: Inovio Pharmaceuticals
First posted: 2018-07-30
Enrollment: 56
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: Inclusion Criteria:

1. Willing and able to provide written informed consent
2. Male or female, age ≥ 18 and ≤ 65 years
3. HIV-1 infection, documented by any licensed rapid HIV test or HIV enzyme or chemiluminescence immunoassay (E/CIA) test kit at any time prior to study entry and confirmed by a licensed Western blot or a second antibody test by a method other than the initial rapid HIV and/or E/CIA, or by HIV-1 antigen or plasma HIV-1 RNA viral load.
4. For Cohort A participants, ART initiated during chronic infection (e.g., more than 6 months after estimated date of infection, or as determined by site investigator and/or available medical records).
5. For Cohort B participants, ART initiated during "hyperacute" HIV infection (Fiebig I/II) or early HIV infection (Fiebig III/IV).
6. On continuous antiretroviral therapy for at least 24 months without any interruptions of greater than 14 consecutive days, and on a stable regimen for at least 8 weeks, without plans to modify ART during the study period
7. Screening plasma HIV RNA levels \< 40 copies/mL on all available determinations in past 24 months (isolated single values ≥ 40 but \< 200 copies/mL will be allowed if they were preceded and followed by undetectable viral load determinations)
8. Screening CD4+ T-cell count ≥ 350 cells/mm3
9. Creatinine Clearance (CrCl) \> 60 mL/min via Cockroft-Gault method at screening
10. The following laboratory criteria must be met at screening:

    * Absolute neutrophil count (ANC) ≥ 1000 neutrophils/mm3
    * Hemoglobin ≥ 10.0 g/dL
    * Platelet count ≥ 100,000/uL
    * Aspartate aminotransferase (AST) ≤ 2x upper limit of normal (ULN)
    * Alanine aminotransferase (ALT) ≤ 2x ULN

Exclusion Criteria:

1. Pregnant, breastfeeding, or unwilling to practice birth control during participation in the study

a. Acceptable birth control is defined as the following: i. For female participants of childbearing potential, two of the following forms of contraception are required, one of which must be a barrier method:

1. Condoms (male of female) with or without a spermicidal agent 2. Diaphragm or cervical cap with spermicide 3. Intrauterine device (IUD) with published data showing that expected failure rate is \< 1% per year 4. Tubal ligation 5. Hormone-based contraceptive such as oral birth control pills ii. Male participants participating in sexual activity that could lead to pregnancy must agree to at least one reliable method of contraception of the above listed 2. Active malignancy requiring systemic chemotherapy or surgery in the preceding 3 months or for whom such therapies are expected in the subsequent 6 months 3. Active (untreated) HCV or HBV infection 4. Decompensated liver disease as defined by the presence of ascites, encephalopathy, esophageal or gastric varices, or persistent jaundice 5. Serious illness requiring systemic treatment and/or hospitalization in the 3 months prior to study enrollment 6. Concurrent treatment with immunomodulatory drugs, and/or exposure to any immunomodulatory drug in the 4 weeks prior to study enrollment (e.g. corticosteroid therapy equal to or exceeding a dose of 15 mg/day of prednisone for more than 10 days, IL-2, interferon-alpha, methotrexate, cancer chemotherapy). NOTE: use of inhaled or nasal steroid is not exclusionary.

7. Serious medical or psychiatric illness that, in the opinion of the site investigator, would interfere with the ability to adhere to study requirements or to give informed consent.

8. Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements or to give informed consent.

9. Unable to undergo leukapheresis procedure 10. Acute or chronic bleeding or clotting disorder that would contraindicate IM injections or use of blood thinners (e.g. anticoagulants or antiplatelet drugs) within 2 weeks of Day 0; 11. Less than two acceptable sites available for IM injection considering the deltoid and anterolateral quadriceps muscles; 12. Tattoos, keloids or hypertrophic scars located within 2 cm of intended treatment site; 13. Cardioverter-defibrillator or pacemaker (to prevent a life-threatening arrhythmia) that is located in ipsilateral deltoid injection site (unless deemed acceptable by a cardiologist); 14. Metal implants or implantable medical device within the intended treatment site (i.e. electroporation area)

Primary outcomes:
measure: The Percentage of Participants With Grade 3 or Higher Treatment-related Adverse Events
timeFrame: Week 64
measure: The Change in the Magnitude of T Cell Responses Will be Evaluated by the IFN-γ Enzyme-linked Immunospot (ELISpot) Assay
timeFrame: Baseline to Week 14
Secondary outcomes:
measure: HIV Reservoir Size
timeFrame: Baseline and Week 64
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of California, Los Angeles
state: California
city: San Francisco
country: United States
facility: Zuckerberg San Francisco General Hospital (ZSFG)
state: California
Study officials:
affiliation: University of California, San Francisco
name: Steven Deeks, MD
role: PRINCIPAL_INVESTIGATOR
References: