HIV Infections
Conditions
Brief summary
The purpose of this study is to evaluate the safety and immune response to three DNA vaccines and a MVA-CMDR vaccine that may boost the immune response to the DNA vaccines in healthy, HIV-uninfected adults.
Detailed description
This study will evaluate the safety, tolerability, and immunogenicity to four different HIV vaccines in healthy, HIV-uninfected adults. The vaccines include three DNA vaccines-DNA Nat-B env, DNA CON-S env, and DNA Mosaic env-and a vaccine called MVA-CMDR that may boost the immune response to the DNA vaccines. The study will enroll healthy, HIV-uninfected participants aged 18 to 50 years. Participants will be randomly assigned to one of three groups and will receive either one of the experimental vaccine regimens or a placebo vaccine regimen. Group 1 participants will receive the DNA Nat-B env and MVA-CMDR vaccines or placebo. Group 2 participants will receive the DNA CON-S env and MVA-CMDR vaccines or placebo. Group 3 participants will receive DNA Mosaic env and MVA-CMDR vaccines or placebo. All participants will receive one of their assigned vaccines at study entry (Month 0), and Months 1, 2, 4, and 8. Total study duration will be either 3 years after enrollment (for participants in the United States) or 5 years after enrollment (for participants in Switzerland). For all participants, study visits will occur at study entry (Month 0), and Months 0.5, 1, 1.5, 2, 2.5, 4, 4.5, 8, 8.25, 8.5, 11, 13.75, and 14. After the last study visit, participants will be contacted annually by phone or e-mail for a total of 3 (U.S. participants) or 5 (Switzerland participants) years to answer questions about their health. All study visits will include a physical exam, HIV risk reduction counseling, and an interview and/or questionnaire. Select study visits will include blood collection, urine and stool collection, HIV testing, an electrocardiogram (ECG), and a pregnancy test for participants who were born female. For participants receiving the MVA-CMDR vaccine, select study visits may also include an assessment of cardiac symptoms.
Interventions
BIOLOGICALDNA Nat-B env
4 mg to be administered as 1 mL intramuscularly (IM) by Biojector 2000® or with a needle and syringe in the deltoid muscle of the non-dominant arm (unless medically contraindicated)
BIOLOGICALDNA CON-S env
4 mg to be administered as 1 mL IM by Biojector 2000® or with a needle and syringe in the deltoid muscle of the non-dominant arm (unless medically contraindicated)
BIOLOGICALDNA Mosaic env
4 mg to be administered as 1 mL IM by Biojector 2000® or with a needle and syringe in the deltoid muscle of the non-dominant arm (unless medically contraindicated)
BIOLOGICALMVA-CMDR
1×10\^8 plaque forming units (pfu) to be administered as 1 mL IM in the deltoid muscle of the non-dominant arm (unless medically contraindicated)
BIOLOGICALPlacebo for DNA Nat-B env
Sodium Chloride for Injection, 0.9% to be administered as 1 mL IM by Biojector 2000® or with a needle and syringe in the deltoid muscle of the non-dominant arm (unless medically contraindicated)
BIOLOGICALPlacebo for DNA CON-S env
Sodium Chloride for Injection, 0.9% to be administered as 1 mL IM by Biojector 2000® or with a needle and syringe in the deltoid muscle of the non-dominant arm (unless medically contraindicated)
BIOLOGICALPlacebo for DNA Mosaic env
Sodium Chloride for Injection, 0.9% to be administered as 1 mL IM by Biojector 2000® or with a needle and syringe in the deltoid muscle of the non-dominant arm (unless medically contraindicated)
BIOLOGICALPlacebo for MVA-CMDR
Sodium Chloride for Injection, 0.9% to be administered as 1 mL IM in the deltoid muscle of the non-dominant arm (unless medically contraindicated)
Sponsors
CHAVI
IPPOX Foundation
MHRP
HIV Vaccine Trials Network
National Institute of Allergy and Infectious Diseases (NIAID)
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
General and Demographic Criteria * 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 * Ability and willingness to provide informed consent * Assessment of understanding: participant demonstrates understanding of this study; completes a questionnaire prior to first vaccination with verbal demonstration of understanding of all questionnaire items answered incorrectly * Willing to be contacted annually after completion of scheduled clinic visits for a total of 3 years for U.S. participants (5 years for participants in Switzerland) following initial study injection * Agrees not to enroll in another study of an investigational research agent * Good general health as shown by medical history, physical exam, and screening laboratory tests HIV-Related Criteria * Willingness to receive HIV test results * Willingness to discuss HIV infection risks and amenable to HIV risk reduction counseling * 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 Hemogram/Complete Blood Count (CBC) * Hemoglobin greater than or equal to 12.5 g/dL for participants who were born female, greater than or equal to 13.5 g/dL for participants 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 * Chemistry panel: alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase less than 1.25 times the institutional upper limit of normal; creatinine less than or equal to the institutional upper limit of normal * Cardiac Troponin T or I (cTnT or cTnI) does not exceed the institutional upper limit of normal Virology * Negative HIV-1 and -2 blood test: U.S. participants must have a negative Food and Drug Administration (FDA)-approved enzyme immunoassay (EIA). Non-U.S. site may use locally available assays that have been approved by HVTN Laboratory Operations. * 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 Urine * Normal urine: * Negative urine glucose, and * Negative or trace urine protein, and * Negative or trace urine hemoglobin (if trace hemoglobin is present on dipstick, a microscopic urinalysis with red blood cells levels within institutional normal range) Reproductive Status * Participants who were born female: negative serum or urine beta human chorionic gonadotropin (beta-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. * Reproductive status: participants who were born female must: * Agree to consistently use effective contraception (information on effective contraception methods can be found in the protocol) 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. * Participants 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
General * Blood products received within 120 days before first vaccination * Investigational research agents received within 30 days before first vaccination * Body mass index (BMI) greater than or equal to 40 * Intent to participate in another study of an investigational research agent during the planned duration of the HVTN 106 study * Pregnant or breastfeeding Vaccines and Other Injections * Smallpox vaccine received within the last 5 years * HIV vaccine(s) received in a prior HIV vaccine trial. For participants who have received control/placebo in an HIV vaccine trial, the HVTN 106 Protocol Safety Review Team (PSRT) will determine eligibility on a case-by-case basis and the identity of the study control/placebo must be obtained. * Non-HIV experimental vaccine(s) received within the last 5 years in a prior vaccine trial. Exceptions may be made for vaccines that have subsequently undergone licensure by the FDA. For participants who have received control/placebo in an experimental vaccine trial, the HVTN 106 PSRT will determine eligibility on a case-by-case basis. For participants who have received an experimental vaccine(s) more than 5 years ago, eligibility for enrollment will be determined by the HVTN 106 PSRT on a case-by-case basis. * Live attenuated vaccines other than influenza vaccine received within 30 days before first vaccination or scheduled within 14 days after injection (e.g., measles, mumps, and rubella \[MMR\]; oral polio vaccine \[OPV\]; varicella; yellow fever) * Influenza vaccine or any vaccines that are not live attenuated vaccines and were received within 14 days prior to first vaccination (e.g., tetanus, pneumococcal, hepatitis A or B) * Allergy treatment with antigen injections within 30 days before first vaccination or that are scheduled within 14 days after first vaccination Immune System * Immunosuppressive medications received within 168 days before first vaccination. (Not excluded: \[1\] corticosteroid nasal spray; \[2\] inhaled corticosteroids; \[3\] topical corticosteroids for mild, uncomplicated dermatitis; or \[4\] a single course of oral/parenteral corticosteroids at doses less than 2 mg/kg/day and length of therapy less than 11 days with completion at least 30 days prior to enrollment * Serious adverse reactions to vaccines or to vaccine components such as neomycin or streptomycin, including anaphylaxis and related symptoms such as hives, respiratory difficulty, angioedema, and/or abdominal pain. (Not excluded: a participant who had a nonanaphylactic adverse reaction to pertussis vaccine as a child) * Immunoglobulin received within 60 days before first vaccination * Autoimmune disease * Immunodeficiency * Hypersensitivity to eggs and/or egg products 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. More information on this criterion can be found in the protocol. * 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 participant'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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Frequency of local and systemic injection site reactogenicity signs and symptoms for each type of vaccine | Measured through Month 8 | — |
| Severity of local and systemic injection site reactogenicity signs and symptoms for each type of vaccine | Measured through Month 8 | — |
| Frequency of adverse events (AEs) | Measured through participant follow-up (3 and 5 years for participants in the United States and Switzerland, respectively) | Categorized by MedDRA body system, MedDRA preferred term, severity, and assessed relationship to study products; detailed description of all AEs meeting Division of AIDS (DAIDS) criteria for expedited reporting (EAE) |
| Laboratory measure of safety: measurement of white blood cells (WBC) | Measured through Month 8 | — |
| Laboratory measure of safety: measurement of neutrophils | Measured through Month 8 | — |
| Laboratory measure of safety: measurement of lymphocytes | Measured through Month 8 | — |
| Laboratory measure of safety: measurement of hemoglobin | Measured through Month 8 | — |
| Laboratory measure of safety: measurement of platelets | Measured through Month 8 | — |
| Laboratory measure of safety: measurement of alanine aminotransferase (ALT) | Measured through Month 8 | — |
| Laboratory measure of safety: measurement of aspartate aminotransferase (AST) | Measured through Month 8 | — |
| Laboratory measure of safety: measurement of alkaline phosphatase | Measured through Month 8 | — |
| Laboratory measure of safety: measurement of creatinine | Measured through Month 8 | — |
| Number of participants with early discontinuation of vaccinations and reason for discontinuation | Measured through Month 8 | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Breadth of HIV-specific binding IgG Env Ab responses 2 weeks after the last MVA vaccination | Measured through Month 8.5 | Determined by BAMA and, for a subset, peptide array |
| Magnitude of HIV-specific binding immunoglobulin A (IgA) Env Ab responses 2 weeks after the last MVA vaccination | Measured through Month 8.5 | Determined by BAMA and, for a subset, peptide array |
| Response rate of CD4 T-cell responses 2 weeks after the last DNA vaccination | Measured through Month 2.5 | Measured by intracellular cytokine staining (ICS) to the Center for HIV/AIDS Vaccine Immunology (CHAVI) and PTEg peptide pools |
| Magnitude of serum neutralizing antibodies (nAbs) to a panel of standardized HIV-1 isolates | Measured through Month 14 | — |
| Breadth of serum nAbs to a panel of standardized HIV-1 isolates | Measured through Month 14 | — |
| Breadth of HIV-specific binding IgA Env Ab responses 2 weeks after the last MVA vaccination | Measured through Month 8.5 | Determined by BAMA and, for a subset, peptide array |
| Total magnitude of CD4 T-cell responses 2 weeks after the last DNA vaccination | Measured through Month 2.5 | Measured by ICS to CHAVI and PTEg peptide pools |
| Response rate of CD8 T-cell responses 2 weeks after the last DNA vaccination | Measured through Month 2.5 | Measured by ICS to CHAVI and PTEg peptide pools |
| Total magnitude of CD8 T-cell responses 2 weeks after the last DNA vaccination | Measured through Month 2.5 | Measured by ICS to CHAVI and PTEg peptide pools |
| Breadth of CD4 T-cell responses determined by epitope mapping, 2 weeks after the last DNA vaccination | Measured through Month 2.5 | Breadth determined as the number of reactive epitopes to the CHAVI and PTEg peptide pools |
| Breadth of CD8 T-cell responses determined by epitope mapping, 2 weeks after the last DNA vaccination | Measured through Month 2.5 | Breadth determined as the number of reactive epitopes to the CHAVI and PTEg peptide pools |
| Response rate of CD4 T-cell responses 2 weeks after each MVA vaccination | Measured through Month 8.5 | Measured by ICS to CHAVI and PTEg peptide pools |
| Total magnitude of CD4 T-cell responses 2 weeks after each MVA vaccination | Measured through Month 8.5 | Measured by ICS to CHAVI and PTEg peptide pools |
| Response rate of CD8 T-cell responses 2 weeks after each MVA vaccination | Measured through Month 8.5 | Measured by ICS to CHAVI and PTEg peptide pools |
| Total magnitude of CD8 T-cell responses 2 weeks after each MVA vaccination | Measured through Month 8.5 | Measured by ICS to CHAVI and PTEg peptide pools |
| Breadth of CD4 T-cell responses determined by epitope mapping, 2 weeks after MVA vaccination | Measured through Month 8.5 | Breadth determined as the number of reactive epitopes to the CHAVI peptide pools and to PTEg peptide pools |
| Breadth of CD8 T-cell responses determined by epitope mapping, 2 weeks after MVA vaccination | Measured through Month 8.5 | Breadth determined as the number of reactive epitopes to the CHAVI peptide pools and to PTEg peptide pools |
| Magnitude of HIV-specific binding immunoglobulin G (IgG) Env antibody (Ab) responses 2 weeks after the last MVA vaccination | Measured through Month 8.5 | Determined by binding Ab multiplex assay (BAMA) and, for a subset, peptide array |
Countries
Switzerland, United States
Outcome results
None listed