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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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, in Healthy, HIV-Uninfected Adult Participants

Conditions
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HIV Infections

Intervention / Treatment
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* 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


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1 (Treatment): p24CE1/2 pDNA + p55^gag pDNA + IL-12 pDNA<br>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<br>* Administered bilaterally using the Ichor Medical Systems Intramuscular TriGrid Delivery System (TDS-IM) electroporation (EP) device<br>* Other names: p24CE1/2;Biological: p55^gag pDNA Vaccine<br>* Administered bilaterally using the TDS-IM EP device<br>* Other names: p55^gag;Biological: IL-12 pDNA Adjuvant<br>* Administered bilaterally using the TDS-IM EP device<br>* Other names: GENEVAX® IL-12 DNA Plasmid;Device: Ichor Medical Systems Intramuscular TriGrid Delivery System (TDS-IM) electroporation (EP) device<br>* The TDS-IM EP device will be used to administer study product(s).<br>* Other names: TDS-IM EP device;|
| Placebo Comparator: Group 1 (Control): Placebo<br>Participants will receive placebo at Day 0 and Months 1, 3, and 6. | Biological: Placebo<br>* Administered bilaterally using the TDS-IM EP device<br>Device: Ichor Medical Systems Intramuscular TriGrid Delivery System (TDS-IM) electroporation (EP) device<br>* The TDS-IM EP device will be used to administer study product(s).<br>* Other names: TDS-IM EP device;|
| Experimental: Group 2 (Treatment): p55^gag pDNA + IL-12 pDNA<br>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<br>* Administered bilaterally using the TDS-IM EP device<br>* Other names: p55^gag;Biological: IL-12 pDNA Adjuvant<br>* Administered bilaterally using the TDS-IM EP device<br>* Other names: GENEVAX® IL-12 DNA Plasmid;Device: Ichor Medical Systems Intramuscular TriGrid Delivery System (TDS-IM) electroporation (EP) device<br>* The TDS-IM EP device will be used to administer study product(s).<br>* Other names: TDS-IM EP device;|
| Placebo Comparator: Group 2 (Control): Placebo<br>Participants will receive placebo at Day 0 and Months 1, 3, and 6. | Biological: Placebo<br>* Administered bilaterally using the TDS-IM EP device<br>Device: Ichor Medical Systems Intramuscular TriGrid Delivery System (TDS-IM) electroporation (EP) device<br>* The TDS-IM EP device will be used to administer study product(s).<br>* Other names: TDS-IM EP device;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV vaccine, DNA vaccine, IL-12, Electroporation, p24, Gag, Adjuvant, Healthy