Clinical trial NCT03181789: Safety and Immunogenicity of pDNA Vaccines Expressing HIV M Group p24^Gag Conserved Elements and/or p55^Gag, Administered With IL-12 pDNA
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, in Healthy, HIV-Uninfected Adult Participants
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: HIV Infections
Keywords: HIV vaccine
DNA vaccine
IL-12
Electroporation
p24
Gag
Adjuvant
Healthy
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
First posted: 2017-06-09
Enrollment: 56
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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
* 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.

Primary outcomes:
measure: Number of Participants Reporting Local Reactogenicity Signs and Symptoms: Pain and/or Tenderness
timeFrame: Measured through Month 0, 1, 3, 6
measure: Number of Participants Reporting Local Reactogenicity Signs and Symptoms: Erythema and/or Induration
timeFrame: Measured through Month 0, 1, 3, 6
measure: Number of Participants Reporting Systemic Reactogenicity Signs and Symptoms
timeFrame: Measured through Month 0, 1, 3, 6
measure: Chemistry and Hematology Laboratory Measures - Alkaline Phosphate (ALP), Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), Creatine Phosphokinase (CPK) in U/L
timeFrame: Measured during screening, Days 14, 42, 98, 182 and 273
measure: Chemistry and Hematology Laboratory Measures - Creatinine in g/dL
timeFrame: Measured during screening, Days 14, 42, 98, 182 and 273
measure: Chemistry and Hematology Laboratory Measures - Hemoglobin in g/dL
timeFrame: Measured during screening, Days 14, 42, 98, 182 and 273
measure: Chemistry and Hematology Laboratory Measures - Lymphocyte Count, Neutrophil Count in 1000*Cells/mm^3
timeFrame: Measured during screening, Days 14, 42, 98, 175 and 273
measure: Chemistry and Hematology Laboratory Measures - Platelets, WBC in 1000*Cells/mm^3
timeFrame: Measured during screening, Days 14, 42, 98, 175 and 273
measure: Number of Participants With Chemistry and Hematology Laboratory Measures - Counts of Lab Grade > 1
timeFrame: 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.
measure: Number of Participants With Early Discontinuation of Vaccinations and Reason for Discontinuation
timeFrame: Measured through Month 18
measure: Magnitude of Local Injection/EP Site Pain as Measured by a Visual Analog Scale (Day 0, Day 28, Day 84, Day 168)
timeFrame: Measured during Day 0, 28, 84 and 168
measure: Distribution of Responses to Questions Regarding Acceptability of Study Injection Procedures [ Visits 3, 5, 8, 10]
timeFrame: Measured during Visit 3 (Day14), Visit 5 (Day 35), Visit 8 (Day 98), Visit 10 (Day 175)
measure: 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]
timeFrame: M1.5 and M6.5
Secondary outcomes:
measure: 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]
timeFrame: M0, M1.5 and M6.5
measure: 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]
timeFrame: M0, M1.5 and M6.5
measure: 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]
timeFrame: M0, M1.5 and M6.5
measure: 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]
timeFrame: M0, M1.5 and M6.5
measure: 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]
timeFrame: M1.5 and M6.5
measure: Binding Antibody IgG Responses Rate by the HIV-1 Binding Antibody Multiplex Assay (BAMA) by Treatment Arm [Time Frame: M6.5]
timeFrame: M6.5
measure: Binding Antibody IgG Responses Magnitudes by the HIV-1 Binding Antibody Multiplex Assay (BAMA) by Treatment Arm [Time Frame: M6.5]
timeFrame: M6.5
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: Bridge HIV CRS
state: California
city: Decatur
country: United States
facility: The Hope Clinic of the Emory Vaccine Center CRS
state: Georgia
city: Cleveland
country: United States
facility: Case Clinical Research Site
state: Ohio
Study officials:
affiliation: Vanderbilt University
name: Spyros Kalams
role: STUDY_CHAIR
affiliation: Bridge HIV, SFDPH
name: Hyman Scott
role: STUDY_CHAIR
References: