HIV Infections
Conditions
Brief summary
The purpose of the study is to evaluate the safety, tolerability, and immunogenicity of polyvalent env (A,B,C,A/E)/gag (C) DNA and gp120 (A,B,C,A/E) protein vaccines (PDPHV201401) co-administered together with or without adjuvant in repeated doses in healthy, HIV-uninfected adults
Detailed description
The purpose of the study is to evaluate the safety, tolerability, and immunogenicity of polyvalent env (A,B,C,A/E)/gag (C) DNA and gp120 (A,B,C,A/E) protein vaccines (PDPHV201401) co-administered together with or without adjuvant in repeated doses in healthy, HIV-uninfected adults. Participants will be enrolled in either Group 1 or 2 with Group 1 being enrolled first to compensate for the longer duration of vaccination period. Within each group, participants will be randomly assigned to either Treatment or Control. Participants in Group 1 (Treatment) will receive polyvalent env (A,B,C,A/E)/gag (C) DNA vaccine in one arm and polyvalent gp120 (A,B,C,A/E) protein vaccine mixed with GLA-SE adjuvant in the other arm on Day 0 and at Months 3, 6, and 12. Participants in Group 1 (Control) will receive placebo on Day 0 and at Months 3, 6, and 12. Participants in Group 2 (Treatment) will receive a mixture of polyvalent env (A,B,C,A/E)/gag (C) DNA vaccine and polyvalent gp120 (A,B,C,A/E) protein vaccine (without GLA-SE adjuvant) divided into two doses and administered into each arm on Day 0 and at Months 1, 3, 6, and 8. Participants in Group 2 (Control) will receive placebo on Day 0 and at Months 1, 3, 6, and 8. Study visits for participants in Group 1 will occur on Day 0, Week 2, Months 3, 3.5, 6, 6.5, 12, 12 + 1 Week, 12.5, 18, and 24. Study visits for participants in Group 2 will occur on Day 0, Week 2, Months 1, 1.5, 3, 3.5, 6, 6.5, 8, 8 + 1 Week, 8.5, 14, and 20. Visits may include physical examination, blood and urine collection, HIV testing, risk reduction counseling, and questionnaires.
Interventions
BIOLOGICALenv (A,B,C,A/E)/gag (C) DNA Vaccine
Administered by intramuscular injection in the deltoid
BIOLOGICALgp120 (A,B,C,A/E) Protein Vaccine
Administered by intramuscular injection in the deltoid
BIOLOGICALGLA-SE adjuvant
Administered by intramuscular injection in the deltoid.
BIOLOGICALPlacebo
Sodium Chloride for Injection, USP 0.9%; Administered by intramuscular injection in the deltoid.
Sponsors
Brigham and Women's Hospital
Access to Advanced Health Institute (AAHI)
Worcester HIV Vaccine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
1. Age of 18 to 50 years 2. Access to BWH trial site and willingness to be followed for the planned duration of the study 3. Ability and willingness to provide informed consent 4. Assessment of understanding: volunteer demonstrates understanding of this study; completes a questionnaire prior to first vaccination with verbal demonstration of understanding of all questionnaire items answered incorrectly 5. Agrees not to enroll in another study of an investigational research agent 6. Good general health as shown by medical history, physical exam, and screening laboratory tests 7. Willingness to receive HIV test results 8. Willingness to discuss HIV infection risks and amenable to HIV risk reduction counseling. 9. 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. HVTN low risk guidelines will be used. Laboratory Inclusion Values Hemogram/CBC 10. Hemoglobin ≥ 11.0 g/dL for volunteers who were born female, ≥ 12.0 g/dL for volunteers who were born male 11. White blood cell count = 3,000 to 12,000 cells/mm3 12. Total lymphocyte count \> 800 cells/mm3 13. Remaining differential either within institutional normal range or with site physician approval 14. Platelets = 125,000 to 450,000/mm3 Chemistry 15. Chemistry panel: ALT, AST, and alkaline phosphatase \< 1.25 times the institutional upper limit of normal; creatinine \< 1.1 times the institutional upper limit of normal. Virology 16. Negative HIV-1 and -2 blood test: US volunteers must have a negative FDA-approved enzyme immunoassay (EIA). 17. Negative Hepatitis B surface antigen (HBsAg) 18. Negative anti-Hepatitis C virus antibodies (anti-HCV), or negative HCV polymerase chain reaction (PCR) if the anti-HCV is positive * Negative urine glucose, and * Negative or trace urine protein, and * Negative, trace, or 1+ urine hemoglobin (if 1+ hemoglobin is present on dipstick, a microscopic urinalysis with red blood cells levels within institutional normal range). Reproductive Status 19. Volunteers who were born female: negative serum or urine beta human chorionic gonadotropin (β-HCG) pregnancy test performed prior to vaccination on the day of initial vaccination. Persons who are NOT of reproductive potential due to having undergone total hysterectomy or bilateral oophorectomy (verified by medical records), are not required to undergo pregnancy testing. 20. Reproductive status: A volunteer who was born female must: * Agree to consistently use effective contraception (see Appendix A and Appendix B) for sexual activity that could lead to pregnancy from at least 21 days prior to enrollment until after the last required protocol clinic visit. Effective contraception is defined as using the following methods: * Condoms (male or female) with or without a spermicide, * Diaphragm or cervical cap with spermicide, * Intrauterine device (IUD), * Hormonal contraception, or * Any other contraceptive method approved by the PSRT * Successful vasectomy in the male partner (considered successful if a volunteer reports that a male partner has \[1\] documentation of azoospermia by microscopy, or \[2\] a vasectomy more than 2 years ago with no resultant pregnancy despite sexual activity post vasectomy); * 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. 21. Volunteers who were born female must also agree not to seek pregnancy through alternative methods, such as artificial insemination or in vitro fertilization until after the last required protocol clinic visit
Exclusion criteria
1. Blood products received within 120 days before first vaccination 2. Investigational research agents received within 30 days before first vaccination 3. Body mass index (BMI) ≥ 40; or BMI ≥ 35 with 2 or more of the following: age \> 45, systolic blood pressure \> 140 mm Hg, diastolic blood pressure \> 90 mm Hg, current smoker, known hyperlipidemia 4. Intent to participate in another study of an investigational research agent or any other study that requires non-HVTN HIV antibody testing 5. Pregnant or breastfeeding 6. Active duty and reserve US military personnel Vaccines and other Injections 7. HIV vaccine(s) received in a prior HIV vaccine trial. 8. Non-HIV experimental vaccine(s) received within the last 5 years in a prior vaccine trial, unless the vaccine subsequently received regulatory approval or emergency authorization. 9. Live attenuated vaccines, other than influenza vaccine, received within 30 days before first vaccination or scheduled within 14 days after injection (eg, measles, mumps, and rubella \[MMR\]; oral polio vaccine \[OPV\]; varicella; yellow fever) 10. Any vaccines that are not live attenuated vaccines and were received within 14 days prior to first vaccination (eg, tetanus, pneumococcal, Hepatitis A or B) 11. Allergy treatment with antigen injections within 30 days before first vaccination or that are scheduled within 14 days after first vaccination Immune System 12. Immunosuppressive medications received within 168 days before first vaccination (Not exclusionary: \[1\] corticosteroid nasal spray; \[2\] inhaled corticosteroids; \[3\] topical immunosuppressives; or \[4\] a single course of oral/parenteral prednisone or equivalent at doses \< 60 mg/day and length of therapy \< 11 days with completion at least 30 days prior to enrollment.) 13. Serious adverse reactions to vaccines or to vaccine components including history of anaphylaxis and related symptoms such as hives, respiratory difficulty, angioedema, and/or abdominal pain. (Not excluded from participation: a volunteer who had a nonanaphylactic adverse reaction to pertussis vaccine as a child.) 14. Immunoglobulin received within 60 days before first vaccination 15. Autoimmune disease, connective tissue disease, or history of vasculitis, eg, leukocytoclastic vasculitis, Henoch-Schonlein Purpura 16. Immunodeficiency Clinically significant medical conditions 17. Untreated or incompletely treated syphilis infection 18. Clinically significant medical condition, physical examination findings, clinically significant abnormal laboratory results, or past medical history with clinically significant implications for current health. A clinically significant condition or process includes but is not limited to: * A process that would affect the immune response, * A process that would require medication that affects the immune response, * Any contraindication to repeated injections or blood draws, * A condition that requires active medical intervention or monitoring to avert grave danger to the volunteer's health or well-being during the study period, * A condition or process for which signs or symptoms could be confused with reactions to vaccine, or * Any condition specifically listed among the
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with early discontinuation of vaccinations | Measured through participants' last study visit, at Month 20 to 24, depending on which part of the study participants are enrolled in | Tabulated by reason and treatment arm |
| Frequency of adverse events (AEs) | Measured through participants' last study visit, at Month 20 to 24, depending on which part of the study participants are enrolled in | AEs categorized by Medical Dictionary for Regulatory Activities (MedDRA) system organ class, MedDRA preferred term, severity, and assessed relationship to study products |
| Severity of local injection site (including DTH) reactogenicity signs and symptoms | Measured through participants' last study visit, at Month 20 to 24, depending on which part of the study participants are enrolled in | Graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017 |
| Severity of systemic reactogenicity signs and symptoms | Measured through participants' last study visit, at Month 20 to 24, depending on which part of the study participants are enrolled in | Graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017 |
| Severity of adverse events (AEs) | Measured through participants' last study visit, at Month 20 to 24, depending on which part of the study participants are enrolled in | AEs categorized by MedDRA system organ class, MedDRA preferred term, severity, and assessed relationship to study products |
| Frequency of local injection site (including DTH) reactogenicity signs and symptoms | Measured through participants' last study visit, at Month 20 to 24, depending on which part of the study participants are enrolled in | Graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017 |
| Frequency of systemic reactogenicity signs and symptoms | Measured through participants' last study visit, at Month 20 to 24, depending on which part of the study participants are enrolled in | Graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serum neutralizing antibody responses against Tier 1A, Tier 1B, and selected Tier 2 viruses | Measured at 2 weeks after the last vaccination | Assessed by TZM-bl assay |
| Breadth of gp70-V1V2 IgG and gp120 IgA | Measured at 2 weeks after the last vaccination | Assessed by ELISA or Binding Antibody Multiplex Assay, and ADCC activities against HIV-1 subtypes A, B, C and A/E |
| Frequency of HIV-1 specific CD4+ and CD8+ T-cell responses | Measured at 2 weeks after the last vaccination | Assessed by intracellular cytokine staining (ICS) |
| Magnitude of serum HIV-1 Env-specific IgG responses | Measured at 2 weeks after the last vaccination | Assessed by ELISA or Binding Antibody Multiplex Assay |
Countries
United States
Outcome results
None listed