Safety and Immunogenicity of pDNA Vaccines Expressing HIV M Group p24^Gag Conserved Elements and/or p55^Gag, Administered With IL-12 pDNA

NCT03181789 | Completed Phase 1 Results DMC FDA Drug FDA Device

• 2 other identifiers: HVTN 11912061
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 3

Brief Summary

The purpose of this study is to evaluate the safety, tolerability, and immunogenicity of two HIV-1 pDNA vaccines: p24CE1/2 pDNA and p55\^gag pDNA administered with IL-12 pDNA adjuvant, given by intramuscular (IM) injection with electroporation (EP), in healthy, HIV-uninfected adults.

Conditions

HIV Infections

Keywords

HIV vaccine; DNA vaccine; IL-12; Electroporation; p24; Gag; Adjuvant; Healthy

Outcome Measures

Primary Outcomes (13)

• Number of Participants Reporting Local Reactogenicity Signs and Symptoms: Pain and/or Tenderness

  Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017. The maximum grade observed for each symptom ove

  Measured through Month 0, 1, 3, 6

• Number of Participants Reporting Local Reactogenicity Signs and Symptoms: Erythema and/or Induration

  Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017. The maximum grade observed for each symptom ove

  Measured through Month 0, 1, 3, 6

• Number of Participants Reporting Systemic Reactogenicity Signs and Symptoms

  Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017. The maximum grade observed for each symptom ove

  Measured through Month 0, 1, 3, 6

• Chemistry and Hematology Laboratory Measures - Alkaline Phosphate (ALP), Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), Creatine Phosphokinase (CPK) in U/L

  For each local laboratory measure-alkaline phosphate (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatine phosphokinase (CPK) in U/L, summary statistics were presented by treatment group and timepoint for the overall population.

  Measured during screening, Days 14, 42, 98, 182 and 273

• Chemistry and Hematology Laboratory Measures - Creatinine in g/dL

  For each local laboratory measure, summary statistics were presented by treatment group and timepoint for the overall population

  Measured during screening, Days 14, 42, 98, 182 and 273

• Chemistry and Hematology Laboratory Measures - Hemoglobin in g/dL

  For each local laboratory measure, summary statistics were presented by treatment group and timepoint for the overall population.

  Measured during screening, Days 14, 42, 98, 182 and 273

• Chemistry and Hematology Laboratory Measures - Lymphocyte Count, Neutrophil Count in 1000*Cells/mm^3

  For each local laboratory measure, summary statistics were presented by treatment group and timepoint for the overall population.

  Measured during screening, Days 14, 42, 98, 175 and 273

• Chemistry and Hematology Laboratory Measures - Platelets, WBC in 1000*Cells/mm^3

  For each local laboratory measure, summary statistics were presented by treatment group and timepoint for the overall population.

  Measured during screening, Days 14, 42, 98, 175 and 273

• Number of Participants With Chemistry and Hematology Laboratory Measures - Counts of Lab Grade > 1

  The number (percentage) of participants with Chemistry and Hematology Laboratory Measures - Counts of Lab Grade \> 1 for alkaline phosphate (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatine phosphokinase (CPK), creatinine, hemoglobin, lymphocyte count, neutrophil count, platelets, white blood cells (WBC) was summarized by treatment group and visit time

  Measured during screening, Days 14, 42, 98, 182 and 273 for (ALP), (AST), (ALT), (CPK), creatinine. Measured during screening, Days 14, 42, 98, 175, 182 and 273 for Lymphocyte count, Neutrophil count Platelets, WBC, hemoglobin.

• Number of Participants With Early Discontinuation of Vaccinations and Reason for Discontinuation

  The number (percentage) of participants with early discontinuation of vaccinations and reason for discontinuation was summarized by arm

  Measured through Month 18

• Magnitude of Local Injection/EP Site Pain as Measured by a Visual Analog Scale (Day 0, Day 28, Day 84, Day 168)

  A visual analog scale is a horizontal line, 10 cm in length, anchored by word descriptors at each end ("no pain" and "worst pain"). The visual analog scale score is determined by measuring in centimeters from the left hand end of the line to the point that the patient marks, 0 cm being no pain and 10 cm being maximum pain.The pain assessment scores for each arm at each vaccination visit were summarized with visual analog scale (VAS)

  Measured during Day 0, 28, 84 and 168

• Distribution of Responses to Questions Regarding Acceptability of Study Injection Procedures [ Visits 3, 5, 8, 10]

  Distribution of responses to questions regarding acceptability of study injection procedures \[ Visits 3, 5, 8, 10\] were summarized by category (Acceptable/Unacceptable/Don?t know/ Don?t Remember)

  Measured during Visit 3 (Day14), Visit 5 (Day 35), Visit 8 (Day 98), Visit 10 (Day 175)

• Summary of T-Cell Epitope Mapping Breadth (Defined as the Number of Targeted CEs) Among All Participants by T-cell Subset (CD4+, CD8+), Visit, and Treatment Arm [Time Frame: Measured at M1.5 and M6.5]

  For participants with a positive Fisher's Exact response to Gag CE Total and/or HBX2 p55Gag for either IFN-γ and/or IL2(CD4+ or CD8+) or for CD40L(CD4+)at month1.5and/or month 6.5, samples were further assayed against the seven individual CE peptide pools and the total number of positive responses was defined as the breadth.

  M1.5 and M6.5

Secondary Outcomes (7)

• CD4+ and CD8+ T Cell Response Rate Measured by Flow Cytometry to p24CE and HIV Gag by Cytokine, T-cell Subset (CD4+, CD8+), Antigen and Treatment Group [Time Frame: Measured at M0, M1.5 and M6.5]

  M0, M1.5 and M6.5

• CD4+ and CD8+ T Cell MIMOSA Response Rate Measured by Flow Cytometry to p24CE and HIV Gag by Cytokine, T-cell Subset (CD4+, CD8+), Antigen and Treatment Group [Time Frame: Measured at M0, M1.5 and M6.5]

  M0, M1.5 and M6.5

• Summary of CD4+ and CD8+ T Cell Response Magnitudes Among All Participants by Cytokine, T-Cell Subset (CD4+, CD8+), Antigen and Treatment Group [Time Frame: Measured at M0, M1.5 and M6.5]

  M0, M1.5 and M6.5

• CD4+ and CD8+ T Cell Response Rate Measured by Flow Cytometry to p24CE and HIV Gag by Cytokine, T-cell Subset (CD4+, CD8+), Antigen and Treatment Group [Time Frame: Measured at M1.5 and M6.5]

  M0, M1.5 and M6.5

• Summary of CD4+ and CD8+ T Cell Response Magnitudes to Epitope Mapping Gag Among All Participants by by Cytokine, T-Cell Subset (CD4+, CD8+), Antigenand Treatment Group [Time Frame: Measured at M1.5 and M6.5]

  M1.5 and M6.5

Study Arms (4)

Group 1 (Treatment): p24CE1/2 pDNA + p55^gag pDNA + IL-12 pDNA

EXPERIMENTAL

Participants will receive the p24CE1/2 pDNA vaccine and the IL-12 pDNA adjuvant at Day 0 and Month 1. They will receive the p24CE1/2 pDNA vaccine plus the p55\^gag pDNA vaccine and the IL-12 pDNA adjuvant at Months 3 and 6.

Biological: p24CE1/2 pDNA Vaccine; Biological: p55^gag pDNA Vaccine; Biological: IL-12 pDNA Adjuvant; Device: Ichor Medical Systems Intramuscular TriGrid Delivery System (TDS-IM) electroporation (EP) device

Group 1 (Control): Placebo

PLACEBO COMPARATOR

Participants will receive placebo at Day 0 and Months 1, 3, and 6.

Biological: Placebo; Device: Ichor Medical Systems Intramuscular TriGrid Delivery System (TDS-IM) electroporation (EP) device

Group 2 (Treatment): p55^gag pDNA + IL-12 pDNA

EXPERIMENTAL

Participants will receive the p55\^gag pDNA vaccine and the IL-12 pDNA adjuvant at Day 0 and Months 1, 3, and 6.

Biological: p55^gag pDNA Vaccine; Biological: IL-12 pDNA Adjuvant; Device: Ichor Medical Systems Intramuscular TriGrid Delivery System (TDS-IM) electroporation (EP) device

Group 2 (Control): Placebo

PLACEBO COMPARATOR

Participants will receive placebo at Day 0 and Months 1, 3, and 6.

Biological: Placebo; Device: Ichor Medical Systems Intramuscular TriGrid Delivery System (TDS-IM) electroporation (EP) device

Interventions

p24CE1/2 pDNA Vaccine BIOLOGICAL

Administered bilaterally using the Ichor Medical Systems Intramuscular TriGrid Delivery System (TDS-IM) electroporation (EP) device

Also known as: p24CE1/2

Group 1 (Treatment): p24CE1/2 pDNA + p55^gag pDNA + IL-12 pDNA

p55^gag pDNA Vaccine BIOLOGICAL

Administered bilaterally using the TDS-IM EP device

Also known as: p55^gag

Group 1 (Treatment): p24CE1/2 pDNA + p55^gag pDNA + IL-12 pDNA; Group 2 (Treatment): p55^gag pDNA + IL-12 pDNA

IL-12 pDNA Adjuvant BIOLOGICAL

Administered bilaterally using the TDS-IM EP device

Also known as: GENEVAX® IL-12 DNA Plasmid

Group 1 (Treatment): p24CE1/2 pDNA + p55^gag pDNA + IL-12 pDNA; Group 2 (Treatment): p55^gag pDNA + IL-12 pDNA

Placebo BIOLOGICAL

Administered bilaterally using the TDS-IM EP device

Group 1 (Control): Placebo; Group 2 (Control): Placebo

Ichor Medical Systems Intramuscular TriGrid Delivery System (TDS-IM) electroporation (EP) device DEVICE

The TDS-IM EP device will be used to administer study product(s).

Also known as: TDS-IM EP device

Group 1 (Control): Placebo; Group 1 (Treatment): p24CE1/2 pDNA + p55^gag pDNA + IL-12 pDNA; Group 2 (Control): Placebo; Group 2 (Treatment): p55^gag pDNA + IL-12 pDNA

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• General and Demographic Criteria
• Age of 18 to 50 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
• Agrees not to enroll in another study of an investigational research agent prior to completion of last required protocol visit (excludes annual health contact visit)
• Good general health as shown by medical history, physical exam, and screening laboratory tests
• HIV-Related Criteria:
• 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.
• Hemoglobin greater than or equal to 11.0 g/dL for volunteers who were born female, greater than or equal to 13.0 g/dL for volunteers 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
• Remaining differential either within institutional normal range or with site physician approval
• Platelets equal to 125,000 to 550,000/mm\^3
• Chemistry panel: alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase less than 1.25 times the institutional upper limit of normal; creatine phosphokinase (CPK) less than or equal to 2.0 times the institutional upper limit of normal; creatinine less than or equal to institutional upper limit of normal.
• Virology
• Negative HIV-1 and -2 blood test: U.S. volunteers must have a negative Food and Drug Administration (FDA)-approved enzyme immunoassay (EIA).

You may not qualify if:

• General
• Allergy to amide-type local anesthetics (bupivacaine \[Marcaine\], lidocaine \[Xylocaine\], mepivacaine \[Polocaine/Carbocaine\], etidocaine \[Duranest\], prilocaine \[Citanest, EMLA® cream\])
• 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 or any other study that requires non-HVTN HIV antibody testing during the planned duration of the study
• Pregnant or breastfeeding
• Active duty and reserve U.S. military personnel
• Vaccines and other Injections
• HIV vaccine(s) received in a prior HIV vaccine trial. For volunteers who have received control/placebo in an HIV vaccine trial, the HVTN Protocol Safety Review Team (PSRT) will determine eligibility on a case-by-case basis.
• Previous receipt of monoclonal antibodies (mAbs), whether licensed or investigational; the HVTN 119 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.
• Immune System
• Immunosuppressive medications received within 168 days before first vaccination.
• Serious adverse reactions to vaccines or to vaccine components
• Autoimmune disease

Sponsors & Collaborators

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

Study Sites (3)

Bridge HIV CRS

San Francisco, California, 94143, United States

Location

The Hope Clinic of the Emory Vaccine Center CRS

Decatur, Georgia, 30030, United States

Location

Case Clinical Research Site

Cleveland, Ohio, 44106, United States

Location

Related Publications (1)

• Kalams SA, Felber BK, Mullins JI, Scott HM, Allen MA, De Rosa SC, Heptinstall J, Tomaras GD, Hu J, DeCamp AC, Rosati M, Bear J, Pensiero MN, Eldridge J, Egan MA, Hannaman D, McElrath MJ, Pavlakis GN; HIV Vaccine Trials Network 119(HVTN 119) Study Team. Focusing HIV-1 Gag T cell responses to highly conserved regions by DNA vaccination in HVTN 119. JCI Insight. 2024 Aug 1;9(18):e180819. doi: 10.1172/jci.insight.180819.

  PMID: 39088271 DERIVED

MeSH Terms

Conditions

HIV Infections

Interventions

Electroporation

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)

Cytological Techniques; Clinical Laboratory Techniques; Investigative Techniques; Electrochemical Techniques

Results Point of Contact

• Title: Jessica Andriesen, PhD, Associate Director of HVTN SDMC Operations
• Organization: Fred Hutchinson Cancer Research Center

jandries@fredhutch.org

206-667-5812

Study Officials

• Spyros Kalams

  Vanderbilt University

  STUDY CHAIR

• Hyman Scott

  Bridge HIV, SFDPH

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

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: June 6, 2017
• First Posted: June 9, 2017
• Study Start: October 18, 2017
• Primary Completion: October 25, 2019
• Study Completion: April 29, 2020
• Last Updated: February 7, 2024
• Results First Posted: October 14, 2021

Record last verified: 2024-01

Locations

US (3)