Evaluating the Safety and Immunogenicity of PENNVAX®-GP DNA Vaccine and IL-12 Plasmid, Delivered Via Intradermal or Intramuscular Electroporation in Healthy, HIV-Uninfected Adults

NCT02431767 | Completed Phase 1 DMC

• 2 other identifiers: HVTN 09811890
• Study Type: interventional
• Target: 94
• Locations: 1 country
• Sites: 4

Brief Summary

The study will evaluate the safety and tolerability of the PENNVAX®-GP HIV-1 DNA vaccine and interleukin 12 (IL-12) DNA adjuvant, given by intradermal (ID) or intramuscular (IM) injection with electroporation (EP), in healthy, HIV-uninfected adults.

Conditions

HIV Infections

Outcome Measures

Primary Outcomes (16)

• Frequency of reactogenicity signs and symptoms

  Measured through Month 18

• Severity of reactogenicity signs and symptoms

  Measured through Month 18

• Magnitude of local injection/EP site pain as measured by a visual analog scale (VAS)

  Measured through Month 18

• Frequency of adverse events (AEs)

  Categorized by MedDRA body system, MedDRA preferred term, severity, and assessed relationship to study products.

  Measured through Month 18

• Measurement of white blood cells

  Measured through Month 12

• Measurement of neutrophils

  Measured through Month 12

• Measurement of lymphocytes

  Measured through Month 12

• Measurement of hemoglobin

  Measured through Month 12

• Measurement of alkaline phosphatase

  Measured through Month 12

• Measurement of platelets

  Measured through Month 12

• Measurement of alanine aminotransferase (ALT)

  Measured through Month 12

• Measurement of aspartate aminotransferase (AST)

  Measured through Month 12

• Measurement of creatinine

  Measured through Month 12

• Measurement of creatine phosphokinase (CPK)

  Measured through Month 12

• Number of participants with early discontinuation of vaccinations

  Measured through Month 12

• Distribution of responses to questions regarding acceptability of study injection procedures

  Measured through Month 12

Secondary Outcomes (5)

• Response rate of CD4+ T-cell responses measured by flow cytometry, to HIV-1-specific peptide pools representing gag, pol, env following the third and fourth vaccinations

  Measured through Month 12

• Response rate of CD8+ T-cell responses measured by flow cytometry, to HIV-1-specific peptide pools representing gag, pol, env following the third and fourth vaccinations

  Measured through Month 12

• Frequency and magnitude of HIV-1 specific binding antibody (Ab) responses as assessed by multiplex assay following the third and fourth vaccinations

  Measured through Month 12

• Neutralizing antibody magnitude and breadth against tier 1 and, if applicable, tier 2 HIV-1 isolates as assessed by area under the magnitude-breadth curves following the third and fourth vaccinations

  Measured through Month 12

• B-cell response rate and magnitude measured by B-cell enzyme-linked immunospot (ELISpot) to quantify Env-specific antibody producing B cells following the third and fourth vaccinations

  Measured through Month 12

Study Arms (8)

Group 1: Treatment

EXPERIMENTAL

Participants will receive the PENNVAX®-GP vaccine 0.6 mg admixed with IL-12 DNA 0.2 mg to be administered as 0.1 mL by intradermal (ID) injection over either deltoid at Months 0, 1, 3, and 6 using the CELLECTRA® 3P EP system.

Biological: PENNVAX®-GP HIV-1 DNA vaccine; Biological: Interleukin-12 (IL-12) DNA adjuvant

Group 1: Placebo

PLACEBO COMPARATOR

Participants will receive placebo to be administered as 0.1 mL ID over either deltoid at Months 0, 1, 3, and 6 using the CELLECTRA® 3P EP system.

Biological: Placebo

Group 2: Treatment

EXPERIMENTAL

Participants will receive the PENNVAX®-GP vaccine 0.8 mg to be administered as 0.1 mL ID over their left and right deltoids (unless medically contraindicated) at Months 0, 1, 3, and 6 using the CELLECTRA® 3P EP system.

Biological: PENNVAX®-GP HIV-1 DNA vaccine

Group 2: Placebo

PLACEBO COMPARATOR

Participants will receive placebo to be administered as 0.1 mL ID over their left and right deltoids (unless medically contraindicated) at Months 0, 1, 3, and 6 using the CELLECTRA® 3P EP system.

Biological: Placebo

Group 3: Treatment

EXPERIMENTAL

Participants will receive the PENNVAX®-GP vaccine 0.8 mg admixed with IL-12 DNA 0.2 mg to be administered as 0.1 mL ID over their left and right deltoids (unless medically contraindicated) at Months 0, 1, 3, and 6 using the CELLECTRA® 3P EP system.

Biological: PENNVAX®-GP HIV-1 DNA vaccine; Biological: Interleukin-12 (IL-12) DNA adjuvant

Group 3: Placebo

PLACEBO COMPARATOR

Participants will receive placebo to be administered as 0.1 mL ID over their left and right deltoids (unless medically contraindicated) at Months 0, 1, 3, and 6 using the CELLECTRA® 3P EP system.

Biological: Placebo

Group 4: Treatment

EXPERIMENTAL

Participants will receive the PENNVAX®-GP vaccine 8 mg admixed with IL-12 DNA 1 mg to be administered as 1 mL intramuscular (IM) injection in either deltoid at Months 0, 1, 3, and 6 using the CELLECTRA® 5P EP system.

Biological: PENNVAX®-GP HIV-1 DNA vaccine; Biological: Interleukin-12 (IL-12) DNA adjuvant

Group 4: Placebo

PLACEBO COMPARATOR

Participants will receive placebo to be administered as 1 mL IM in either deltoid at Months 0, 1, 3, and 6 using the CELLECTRA® 5P EP system.

Biological: Placebo

Interventions

PENNVAX®-GP HIV-1 DNA vaccine BIOLOGICAL

Administered by intradermal (ID) injection in Groups 1, 2, and 3; administered by intramuscular (IM) injection in Group 4.

Group 1: Treatment; Group 2: Treatment; Group 3: Treatment; Group 4: Treatment

Interleukin-12 (IL-12) DNA adjuvant BIOLOGICAL

Administered by intradermal (ID) injection in Groups 1, 2, and 3; administered by intramuscular (IM) injection in Group 4.

Group 1: Treatment; Group 3: Treatment; Group 4: Treatment

Placebo BIOLOGICAL

Sterile Water for Injection, USP. Administered by intradermal (ID) injection in Groups 1, 2, and 3; administered by intramuscular (IM) injection in Group 4.

Group 1: Placebo; Group 2: Placebo; Group 3: Placebo; Group 4: Placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• General and Demographic Criteria:
• Age of 18 to 55 years
• Access to a participating HIV Vaccine Trials Network (HVTN) clinical research site (CRS) and willingness to be followed for the planned duration of the study
• Ability and willingness to provide informed consent
• Assessment of understanding: participant demonstrates understanding of this study; completes a questionnaire prior to first vaccination with verbal demonstration of understanding of all questionnaire items answered incorrectly
• Agrees not to enroll in another study of an investigational research agent
• Good general health as shown by medical history, physical exam, and screening laboratory tests
• HIV-Related Criteria:
• Willingness to receive HIV test results
• Willingness to discuss HIV infection risks and amenable to HIV risk reduction counseling
• Assessed by the clinic staff as being at "low risk" for HIV infection and committed to maintaining behavior consistent with low risk of HIV exposure through the last required protocol clinic visit
• Hemogram/Complete Blood Count (CBC)
• Hemoglobin greater than or equal to 11.0 g/dL for participants who were born female, greater than or equal to 13.0 g/dL for participants who were born male
• White blood cell count equal to 3,300 to 12,000 cells/mm\^3
• Total lymphocyte count greater than or equal to 800 cells/mm\^3

You may not qualify if:

• General:
• Blood products received within 120 days before first vaccination
• Investigational research agents received within 30 days before first vaccination
• Body mass index (BMI) greater than or equal to 40; or BMI greater than or equal to 35 with 2 or more of the following: age greater than 45, systolic blood pressure greater than 140 mm Hg, diastolic blood pressure greater than 90 mm Hg, current smoker, known hyperlipidemia
• Intent to participate in another study of an investigational research agent during the planned duration of the HVTN 098 study
• Pregnant or breastfeeding
• Subcutaneous contraceptive device
• Vaccines and Other Injections:
• HIV vaccine(s) received in a prior HIV vaccine trial. For participants who have received control/placebo in an HIV vaccine trial, the HVTN 098 Protocol Safety Review Team (PSRT) will determine eligibility on a case-by-case basis.
• Non-HIV experimental vaccine(s) received within the last 5 years in a prior vaccine trial. Exceptions may be made for vaccines that have subsequently undergone licensure by the FDA. For participants who have received control/placebo in an experimental vaccine trial, the HVTN 098 PSRT will determine eligibility on a case-by-case basis. For participants who have received an experimental vaccine(s) greater than 5 years ago, eligibility for enrollment will be determined by the HVTN 098 PSRT on a case-by-case basis.
• Live attenuated vaccines other than influenza vaccine received within 30 days before first vaccination or scheduled within 14 days after injection (e.g., measles, mumps, and rubella \[MMR\]; oral polio vaccine \[OPV\]; varicella; yellow fever)
• Influenza vaccine or any vaccines that are not live attenuated vaccines and were received within 14 days prior to first vaccination (e.g., tetanus, pneumococcal, hepatitis A or B)
• Allergy treatment with antigen injections within 30 days before first vaccination or that are scheduled within 14 days after first vaccination
• Immune System:
• Immunosuppressive medications received within 168 days before first vaccination. (Not excluded: \[1\] corticosteroid nasal spray; \[2\] low-dose inhaled corticosteroids; \[3\] topical corticosteroids for mild, uncomplicated dermatitis; or \[4\] a single course of oral/parenteral corticosteroids at doses less than 2 mg/kg/day and length of therapy less than 11 days with completion at least 30 days prior to enrollment.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (4)

The Hope Clinic of the Emory Vaccine Center CRS

Decatur, Georgia, 30030, United States

Location

University of Rochester Vaccines to Prevent HIV Infection CRS

Rochester, New York, 14642, United States

Location

Vanderbilt Vaccine (VV) CRS

Nashville, Tennessee, 37232-2582, United States

Location

Seattle Vaccine and Prevention CRS

Seattle, Washington, 98109-1024, United States

Location

Related Publications (1)

• De Rosa SC, Edupuganti S, Huang Y, Han X, Elizaga M, Swann E, Polakowski L, Kalams SA, Keefer MC, Maenza J, Lu Y, Wise MC, Yan J, Morrow MP, Khan AS, Boyer JD, Humeau L, White S, Pensiero M, Sardesai NY, Bagarazzi ML, Weiner DB, Ferrari G, Tomaras GD, Montefiori DC, Corey L, McElrath MJ; HIV Vaccine Trials Network (HVTN) 098 Study Team. Robust antibody and cellular responses induced by DNA-only vaccination for HIV. JCI Insight. 2020 Jul 9;5(13):e137079. doi: 10.1172/jci.insight.137079.

  PMID: 32437332 DERIVED

MeSH Terms

Conditions

HIV Infections

Interventions

Interleukin-12

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; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Officials

• Srilatha Edupuganti

  Emory University

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 28, 2015
• First Posted: May 1, 2015
• Study Start: August 1, 2015
• Primary Completion: June 8, 2017
• Study Completion: December 20, 2017
• Last Updated: October 15, 2021

Record last verified: 2021-10

Locations

US (4)