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

NCT ID: NCT03181789

Last Updated: 2024-02-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 56 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-10-18
• Study Completion Date: 2020-04-29

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.

Detailed Description

This study will 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.

Participants will be randomly assigned to one of four groups: Group 1 Treatment, Group 1 Control, Group 2 Treatment, or Group 2 Control.

Participants in Group 1 Treatment will receive p24CE1/2 pDNA and IL-12 pDNA at Day 0 and Month 1, then p24CE1/2 pDNA plus p55^gag pDNA and IL-12 pDNA at Months 3 and 6. Participants in Group 1 Control will receive placebo (sodium chloride for injection) at Day 0 and Months 1, 3, and 6.

Participants in Group 2 Treatment will receive p55^gag pDNA and IL-12 pDNA at Day 0 and Months 1, 3, and 6. Participants in Group 2 Control will receive placebo (sodium chloride for injection) at Day 0 and Months 1, 3, and 6.

Study visits will occur at Day 0, Week 2, and Months 1, 1.25, 1.5, 3, 3.5, 6, 6.25, 6.5, 9, and 12. Visits may include physical examinations and clinical assessments, blood and urine collection, optional stool collection, HIV testing, risk reduction counseling, and interviews/questionnaires. At Month 18, study staff will contact participants for follow-up health monitoring.

Conditions

HIV Infections

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

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

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.

Group Type: EXPERIMENTAL

p24CE1/2 pDNA Vaccine

Intervention Type: BIOLOGICAL

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

p55^gag pDNA Vaccine

Intervention Type: BIOLOGICAL

Administered bilaterally using the TDS-IM EP device

IL-12 pDNA Adjuvant

Intervention Type: BIOLOGICAL

Administered bilaterally using the TDS-IM EP device

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

Intervention Type: DEVICE

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

Group 1 (Control): Placebo

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: BIOLOGICAL

Administered bilaterally using the TDS-IM EP device

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

Intervention Type: DEVICE

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

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

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

Group Type: EXPERIMENTAL

p55^gag pDNA Vaccine

Intervention Type: BIOLOGICAL

Administered bilaterally using the TDS-IM EP device

IL-12 pDNA Adjuvant

Intervention Type: BIOLOGICAL

Administered bilaterally using the TDS-IM EP device

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

Intervention Type: DEVICE

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

Group 2 (Control): Placebo

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: BIOLOGICAL

Administered bilaterally using the TDS-IM EP device

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

Intervention Type: DEVICE

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

Interventions

p24CE1/2 pDNA Vaccine

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

Intervention Type: BIOLOGICAL

p55^gag pDNA Vaccine

Administered bilaterally using the TDS-IM EP device

Intervention Type: BIOLOGICAL

IL-12 pDNA Adjuvant

Administered bilaterally using the TDS-IM EP device

Intervention Type: BIOLOGICAL

Placebo

Administered bilaterally using the TDS-IM EP device

Intervention Type: BIOLOGICAL

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

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

Intervention Type: DEVICE

Other Intervention Names

p24CE1/2; p55^gag; GENEVAX® IL-12 DNA Plasmid; TDS-IM EP device

Eligibility Criteria

Inclusion Criteria

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.

Laboratory Inclusion Values

• 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).
• Negative Hepatitis B surface antigen (HBsAg)
• Negative anti-Hepatitis C virus antibodies (anti-HCV), or negative HCV polymerase chain reaction (PCR) if the anti-HCV is positive
• Normal urine:

• Negative urine glucose, and
• Negative or trace urine protein, and
• Negative or trace urine hemoglobin

Reproductive Status

• Reproductive status: A volunteer who was born female must:

• Agree to consistently use effective contraception for sexual activity that could lead to pregnancy from at least 21 days prior to enrollment through the last required protocol clinic visit.
• Or not be of reproductive potential, such as having reached menopause (no menses for 1 year) or having undergone hysterectomy, bilateral oophorectomy, or tubal ligation;
• Or be sexually abstinent.

Exclusion Criteria

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
• Immunodeficiency

Clinically significant medical conditions

• Untreated or incompletely treated syphilis infection
• Clinically significant medical condition, physical examination findings, clinically significant abnormal laboratory results, or past medical history with clinically significant implications for current health.
• Any medical, psychiatric, occupational, or other condition that, in the judgment of the investigator, would interfere with, or serve as a contraindication to, protocol adherence, assessment of safety or reactogenicity, or a volunteer's ability to give informed consent
• Psychiatric condition that precludes compliance with the protocol. Specifically excluded are persons with psychoses within the past 3 years, ongoing risk for suicide, or history of suicide attempt or gesture within the past 3 years.
• Current anti-tuberculosis (TB) prophylaxis or therapy
• Diabetes mellitus type 1 or type 2, including cases controlled with diet alone. (Not excluded: history of isolated gestational diabetes.)
• Thyroidectomy, or thyroid disease requiring medication during the last 12 months
• Hypertension
• Bleeding disorder diagnosed by a doctor (e.g., factor deficiency, coagulopathy, or platelet disorder requiring special precautions)
• Malignancy
• Seizure disorder
• Asplenia
• History of hereditary angioedema, acquired angioedema, or idiopathic angioedema.
• Presence of implanted electronic medical device (e.g., cochlear implant, pacemaker, implantable cardioverter defibrillator)
• Presence of surgical or traumatic metal implant at the intended site of administration (including the deltoid muscles and/or overlying skin)
• Sinus bradycardia (defined as less than 50 beats per minute (bpm) on exam) or a history of cardiac arrhythmia: e.g., supraventricular tachycardia, atrial fibrillation, or frequent ectopy. NOTE: Sinus arrhythmia is not excluded.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Spyros Kalams

Role: STUDY_CHAIR

Vanderbilt University

Hyman Scott

Role: STUDY_CHAIR

Bridge HIV, SFDPH

Locations

Bridge HIV CRS

San Francisco, California, United States

The Hope Clinic of the Emory Vaccine Center CRS

Decatur, Georgia, United States

Case Clinical Research Site

Cleveland, Ohio, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 39088271 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

12061

Identifier Type: REGISTRY

Identifier Source: secondary_id

HVTN 119

Identifier Type: -

Identifier Source: org_study_id