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
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- HIV Infections
- Sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)
- Enrollment
- 56
- Locations
- 3
- Primary Endpoint
- Chemistry and Hematology Laboratory Measures - Creatinine in g/dL
- Status
- Completed
- Last Updated
- 2 years ago
Overview
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.
Investigators
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
Exclusion Criteria
- •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.
Outcomes
Primary Outcomes
Chemistry and Hematology Laboratory Measures - Creatinine in g/dL
Time Frame: Measured during screening, Days 14, 42, 98, 182 and 273
For each local laboratory measure, summary statistics were presented by treatment group and timepoint for the overall population
Number of Participants Reporting Local Reactogenicity Signs and Symptoms: Pain and/or Tenderness
Time Frame: Measured through Month 0, 1, 3, 6
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
Number of Participants Reporting Local Reactogenicity Signs and Symptoms: Erythema and/or Induration
Time Frame: Measured through Month 0, 1, 3, 6
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
Number of Participants With Chemistry and Hematology Laboratory Measures - Counts of Lab Grade > 1
Time Frame: 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.
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
Number of Participants With Early Discontinuation of Vaccinations and Reason for Discontinuation
Time Frame: Measured through Month 18
The number (percentage) of participants with early discontinuation of vaccinations and reason for discontinuation was summarized by arm
Magnitude of Local Injection/EP Site Pain as Measured by a Visual Analog Scale (Day 0, Day 28, Day 84, Day 168)
Time Frame: Measured during Day 0, 28, 84 and 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)
Number of Participants Reporting Systemic Reactogenicity Signs and Symptoms
Time Frame: Measured through Month 0, 1, 3, 6
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
Chemistry and Hematology Laboratory Measures - Alkaline Phosphate (ALP), Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), Creatine Phosphokinase (CPK) in U/L
Time Frame: Measured during screening, Days 14, 42, 98, 182 and 273
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.
Chemistry and Hematology Laboratory Measures - Lymphocyte Count, Neutrophil Count in 1000*Cells/mm^3
Time Frame: Measured during screening, Days 14, 42, 98, 175 and 273
For each local laboratory measure, summary statistics were presented by treatment group and timepoint for the overall population.
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]
Time Frame: 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.
Chemistry and Hematology Laboratory Measures - Hemoglobin in g/dL
Time Frame: Measured during screening, Days 14, 42, 98, 182 and 273
For each local laboratory measure, summary statistics were presented by treatment group and timepoint for the overall population.
Chemistry and Hematology Laboratory Measures - Platelets, WBC in 1000*Cells/mm^3
Time Frame: Measured during screening, Days 14, 42, 98, 175 and 273
For each local laboratory measure, summary statistics were presented by treatment group and timepoint for the overall population.
Distribution of Responses to Questions Regarding Acceptability of Study Injection Procedures [ Visits 3, 5, 8, 10]
Time Frame: Measured during Visit 3 (Day14), Visit 5 (Day 35), Visit 8 (Day 98), Visit 10 (Day 175)
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)
Secondary Outcomes
- 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)
- 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)
- Binding Antibody IgG Responses Rate by the HIV-1 Binding Antibody Multiplex Assay (BAMA) by Treatment Arm [Time Frame: M6.5](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)
- 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)
- Binding Antibody IgG Responses Magnitudes by the HIV-1 Binding Antibody Multiplex Assay (BAMA) by Treatment Arm [Time Frame: M6.5](M6.5)