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Evaluating the Safety and Immunogenicity of pDNA Vaccines Expressing HIV M Group p24^Gag Conserved Elements and/or p55^Gag, Administered With IL-12 pDNA by Intramuscular Electroporation, in Healthy, HIV-Uninfected Adults (HVTN 119)

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ClinicalTrials.gov Identifier: NCT03181789
Recruitment Status : Active, not recruiting
First Posted : June 9, 2017
Last Update Posted : November 14, 2018
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

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.

Condition or disease Intervention/treatment Phase
HIV Infections Biological: p24CE1/2 pDNA Vaccine Biological: p55^gag pDNA Vaccine Biological: IL-12 pDNA Adjuvant Biological: Placebo Device: Ichor Medical Systems Intramuscular TriGrid Delivery System (TDS-IM) electroporation (EP) device Phase 1

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.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 56 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: A Phase 1 Clinical Trial to Evaluate the Safety and Immunogenicity of pDNA Vaccines Expressing HIV M Group p24^Gag Conserved Elements and/or p55^Gag, Administered With IL-12 pDNA by Intramuscular Electroporation, in Healthy, HIV-Uninfected Adult Participants
Actual Study Start Date : October 18, 2017
Estimated Primary Completion Date : October 28, 2019
Estimated Study Completion Date : April 27, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Arm Intervention/treatment
Experimental: 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.
Biological: p24CE1/2 pDNA Vaccine
Administered bilaterally using the Ichor Medical Systems Intramuscular TriGrid Delivery System (TDS-IM) electroporation (EP) device
Other Name: p24CE1/2

Biological: p55^gag pDNA Vaccine
Administered bilaterally using the TDS-IM EP device
Other Name: p55^gag

Biological: IL-12 pDNA Adjuvant
Administered bilaterally using the TDS-IM EP device
Other Name: GENEVAX® IL-12 DNA Plasmid

Device: 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).
Other Name: TDS-IM EP device

Placebo Comparator: Group 1 (Control): Placebo
Participants will receive placebo at Day 0 and Months 1, 3, and 6.
Biological: Placebo
Administered bilaterally using the TDS-IM EP device

Device: 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).
Other Name: TDS-IM EP device

Experimental: 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.
Biological: p55^gag pDNA Vaccine
Administered bilaterally using the TDS-IM EP device
Other Name: p55^gag

Biological: IL-12 pDNA Adjuvant
Administered bilaterally using the TDS-IM EP device
Other Name: GENEVAX® IL-12 DNA Plasmid

Device: 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).
Other Name: TDS-IM EP device

Placebo Comparator: Group 2 (Control): Placebo
Participants will receive placebo at Day 0 and Months 1, 3, and 6.
Biological: Placebo
Administered bilaterally using the TDS-IM EP device

Device: 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).
Other Name: TDS-IM EP device




Primary Outcome Measures :
  1. Frequency of local injection/electroporation (EP) site reactogenicity signs/symptoms [ Time Frame: Measured through Month 6.5 ]
    Signs/symptoms may include erythema/redness and induration/swelling.

  2. Severity of local injection/EP site reactogenicity signs/symptoms [ Time Frame: Measured through Month 6.5 ]
    Graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1, March 2017

  3. Frequency of systemic reactogenicity signs/symptoms [ Time Frame: Measured through Month 6.5 ]
    Signs/symptoms may include increased body temperature, malaise and/or fatigue, myalgia, headache, chills, arthralgia, nausea, and vomiting.

  4. Severity of systemic reactogenicity signs/symptoms [ Time Frame: Measured through Month 6.5 ]
    Graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1, March 2017

  5. Frequency of adverse events (AEs) [ Time Frame: Measured through Month 18 ]
    Categorized by MedDRA body system, MedDRA preferred term, severity and assessed relationship to study products.

  6. The distribution of values of safety laboratory measures at baseline and at follow-up visits post vaccination [ Time Frame: Measured through Month 9 ]
    Based on laboratory evaluations

  7. Number of participants with early discontinuation of vaccinations [ Time Frame: Measured through Month 6 ]
    Circumstances may include co-enrollment in a study with an investigational research agent or clinically significant condition

  8. Magnitude of local injection/EP site pain [ Time Frame: Measured through Month 6 ]
    As measured by a visual analog scale

  9. Distribution of responses to questions regarding acceptability of study injection procedures [ Time Frame: Measured through Month 6.5 ]
    Determined by participant responses on acceptability questionnaire

  10. The number of targeted conserved elements (CEs) by CD4+ and CD8+ T-cell responses [ Time Frame: Measured through Month 12 ]
    Measured by intracellular cytokine staining (ICS) 2 weeks after the second and fourth vaccinations


Secondary Outcome Measures :
  1. Rate of CD4+ and CD8+ T-cell responses [ Time Frame: Measured through Month 12 ]
    Measured by ICS to p24CE and HIV Gag, 2 weeks after the second and fourth vaccinations

  2. Epitope specificity of T-cell responses [ Time Frame: Measured through Month 12 ]
    Measured by interferon gamma (IFN-gamma) ELISpot to p24CE and HIV Gag, 2 weeks after the second and fourth vaccinations

  3. Rate of humoral immune responses to Gag measured 2 weeks after the 4th vaccination [ Time Frame: Measured through Month 12 ]
    Measured by binding antibody multiplex assay

  4. Rate of CD4+ circulating Tfh counterparts (cTfh) [ Time Frame: Measured through Month 12 ]
    Measured by ICS



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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
  • Asthma exclusion criteria: Asthma other than mild, well-controlled asthma.
  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03181789


Locations
United States, California
Bridge HIV CRS
San Francisco, California, United States, 94143
United States, Georgia
The Hope Clinic of the Emory Vaccine Center CRS
Decatur, Georgia, United States, 30030
United States, Ohio
Case Clinical Research Site
Cleveland, Ohio, United States, 44106
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
Investigators
Study Chair: Spyros Kalams Vanderbilt University
Study Chair: Hyman Scott Bridge HIV, SFDPH

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT03181789     History of Changes
Other Study ID Numbers: HVTN 119
12061 ( Registry Identifier: DAIDS-ES Registry Number )
First Posted: June 9, 2017    Key Record Dates
Last Update Posted: November 14, 2018
Last Verified: November 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: No

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
HIV vaccine
DNA vaccine
IL-12
Electroporation
p24
Gag
Adjuvant
Healthy

Additional relevant MeSH terms:
HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Vaccines
Interleukin-12
Immunologic Factors
Physiological Effects of Drugs
Adjuvants, Immunologic
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Antineoplastic Agents