HIV Infections
Conditions
Keywords
HIV
Brief summary
The purpose of this study is to evaluate the safety and immunogenicity of 426c.Mod.Core-C4b vaccine adjuvanted with 3M-052-AF + Alum in infants with perinatal HIV exposure who are without HIV at birth
Detailed description
This study will compare the safety and immunogenicity of an experimental HIV vaccine in infants with perinatal HIV exposure who are without HIV at birth. The study vaccine is called 426c.Mod.Core-C4b. The vaccine is mixed with an adjuvant called 3M-052-AF + Alum. This study is divided into 2 parts: Part A and B. Part A has 4 groups, while Part B has 2 groups. Part A of the study is testing the vaccine alone or in combination with different doses of adjuvant. Part B is testing study vaccine and the safest dose of adjuvants from Part A versus placebo. Depending on their group, participants will receive 426c.Mod.Core-C4b, 426c.Mod.Core-C4b vaccine adjuvanted with 3M-052-AF + Alum, or a placebo by injection at Months 0, 3, and 7. Additional study visits will occur at Day 1, Week 2, Month 3 1/2, Month 7 1/2, Month 10, Year 1, Year 1 1/2, and Year 1 3/4. Study visits may include physical exams, blood and saliva collection for the infants and questionnaires, counselling, blood, and optional breastmilk collection for the mothers of infants.
Interventions
BIOLOGICAL426c.Mod.Core-C4b
self-assembling nanoparticle expressing up to 7 molecules of the 426c.Mod.Core envelope immunogen.
BIOLOGICAL3M-052-AF
3M-052-AF is an aqueous formulation (AF) of a lipidated small molecule imidazoquinoline that is a Toll-like receptor (TLR)7/8 and inflammasome agonist. To be administered as 0.3 mcg, 0.75 mcg, or 1.5 mcg admixed with 426c.Mod.Core-C4b, with Alum
BIOLOGICALAluminum hydroxide suspension (Alum)
Aluminum hydroxide suspension (Alum) to be administered as 250 mcg (aluminum content) admixed with 426c.Mod.Core-C4b with 3M-052-AF.
BIOLOGICALPlacebo and Diluent
Tris-NaCl buffer.
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Fred Hutchinson Cancer Center
Access to Advanced Health Institute
HIV Vaccine Trials Network
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Part A will be open label.
Intervention model description
Part A is dose escalating. Part B is parallel.
Eligibility
Sex/Gender
ALL
Age
No minimum to 7 Days
Healthy volunteers
Yes
Inclusion criteria
Mother * Mother's age is at least 18 years and is willing and able to provide written informed consent for their and their infant's participation in this study * Mother is in the second or third trimester of singleton pregnancy, as determined by a clinical exam or sonography and reported menstrual history * Mother agrees to donate umbilical cord blood * Mother has a planned Caesarian delivery at Chris Hani Baragwanath Academic Hospital (Soweto) and plans to remain in the area after delivery and through study duration * Mother is determined by the site investigator to be in good overall health at the time of delivery based on medical history and physical exam * Mother has a documented CD4 count of more than 350 cells/mcL at screening * Mother has been on cART for at least 16 weeks prior to delivery and intends to continue with cART for the duration of breastfeeding * Mother has a viral load of less than 400 copies/mL between 2 weeks before and 7 days after delivery * Mother has access to the participating HVTN CRS and is willing to be followed for the planned duration of the study * Mother demonstrates understanding of this study and is able and willing to complete the informed consent process and delivery with verbal demonstration of understanding of all questionnaire items answered incorrectly * Mother agrees not to enroll either self or infant in another research study for the duration of the trial without prior approval of the HVTN 316 PSRT. * Mother has confirmed positive HIV-1 status documented by medical records at any time during or prior to screening, and confirmed by the HVTN CRS by serology
Exclusion criteria
Mother * Any World Health Organization (WHO) grade IV illness within 1 year prior to study enrollment, as determined by the history and physical examination and review of the medical record (if available). These include HIV wasting syndrome; PJP pneumonia; cerebral toxoplasmosis; extrapulmonary cryptococcosis; progressive multifocal leukoencephalopathy; any disseminated endemic mycosis (histoplasmosis); candidiasis of the esophagus, trachea, bronchi, or lung; disseminated atypical mycobacteria; non-typhoid salmonella septicemia; extrapulmonary tuberculosis; lymphoma; and Kaposi's sarcoma. * Prior participation in any HIV-1 vaccine or anti-HIV antibody-mediated prevention trial * Receipt of any investigational agent during this pregnancy * Receipt of blood products, immunoglobulin (Ig), or immunomodulating therapy within 45 days prior to, and the day of delivery * 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 infant safety or reactogenicity, or a volunteer's ability to give informed consent * Any condition that places the newborn at higher risk of early-onset sepsis, such as concern for active maternal infection at delivery, as determined by local site investigators (eg, fever) * Detectable hepatitis B surface antigen (HBsAg) Inclusion Criteria: Infant * Born via Caesarean delivery to a pregnant woman living with HIV-1 who meets all maternal inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants reporting local reactogenicity signs and symptoms and number of local reactogenicity signs and symptoms experienced by each participant | Measured through 14 days following receipt of study product at day 5, week 12, and week 28 | Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 \[March 2017\] |
| Number of participants reporting systemic reactogenicity signs and symptoms symptoms and number of systemic reactogenicity signs and symptoms experienced by each participant, | Measured through 14 days following receipt of study product at day 5, week 12, and week 28 | Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 \[March 2017\] |
| Number of participants reporting adverse events and overall number of adverse events | Measured through out the study period | Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 \[March 2017\] |
| Number of participants reporting serious adverse events and overall number of serious adverse events | Measured through 12 months post last vaccination at week 28 | Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 \[March 2017\] |
| Number of participants reporting medically attended adverse events and overall number of medically attended adverse events | Measured through 12 months post last vaccination at week 28 | Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 \[March 2017\] |
| Number of participants reporting adverse events of special interest (AESIs) that are Potential Immune Mediated Medical Conditions (PIMMCs) and overall number of AESIs that are PIMMCs | Measured through 12 months post last vaccination at week 28 | Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 \[March 2017\] |
| Number of participants reporting AEs leading to early participant withdrawal or permanent discontinuation | Measured through 12 months post last vaccination at week 28 | Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 \[March 2017\] |
| Response rate of CD4bs-specific IgG binding antibodies | Measured 2 weeks after the 3rd vaccination at week 28 | Measured by binding antibody multiplex assay (BAMA) |
| Magnitude of CD4bs-specific IgG binding antibodies | Measured 2 weeks after the 3rd vaccination at week 28 | Measured by binding antibody multiplex assay (BAMA) |
| Response rate of CD4bs-specific memory B cells | Measured 2 weeks after the 3rd vaccination at week 28 | Measured by flow cytometry |
| Magnitude of CD4bs-specific memory B cells | Measured 2 weeks after the 3rd vaccination at week 28 | Measured by flow cytometry |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Magnitude of serum neutralization | Measured 6 months and 12 months after the 3rd vaccination at week 28 | Measured by TZM-bl assay |
| Response rate of serum Ab neutralization of vaccine-matched viruses | Measured 2 weeks after the 3rd vaccination at week 28 | Measured by TZM-bl pseudoneutralization assay |
| EPI vaccine-specific binding antibody responses | Measured 2 weeks, 6 months, and 12 months after the 3rd vaccination at week 28 | Assessed by Pediatric Vaccine Multiplex Assay (PVMA) |
| Magnitude of serum Ab neutralization of vaccine-matched viruses | Measured 2 weeks after the 3rd vaccination at week 28 | Measured by TZM-bl pseudoneutralization assay |
| Differential neutralization of HIV-1 strains that are diagnostic for CD4bs bNAb precursors | Measured 2 weeks after the 3rd vaccination at week 28 | Measured by TZM-bl assay |
| Response rate of serum Ab neutralization of heterologous HIV-1 strains | Measured 2 weeks after the 3rd vaccination at week 28 | Measured by TZM-bl assay |
| Magnitude of serum Ab neutralization of heterologous HIV-1 strains | Measured 2 weeks after the 3rd vaccination at week 28 | Measured by TZM-bl assay |
| Response rate (i.e., percentage) of CD4bs-specific, including VRC01-class, B cells | Measured 2 weeks after the 3rd vaccination at week 28 | Measured by BCR sequencing of sorted B cells |
| Magnitude of CD4bs-specific, including VRC01-class, B cells | Measured 2 weeks after the 3rd vaccination at week 28 | Measured by BCR sequencing of sorted B cells |
| Response rate of vaccine-specific and CD4bs-specific binding antibodies | Measured 6 months and 12 months after the 3rd vaccination at week 28 | Measured by BAMA |
| Magnitude of vaccine-specific and CD4bs-specific binding antibodies | Measured 6 months and 12 months after the 3rd vaccination at week 28 | Measured by BAMA |
| Response rate of CD4bs-specific memory B cells | Measured 6 months and 12 months after the 3rd vaccination at week 28 | Measured by flow cytometry |
| Response rate of serum neutralization | Measured 6 months and 12 months after the 3rd vaccination at week 28 | Measured by TZM-bl assay |
Countries
South Africa
Contacts
Primary ContactClinical Trials Manager
Outcome results
None listed