Safety & Immunogenicity of 426c.Mod.Core-C4b Vaccine With 3M-052-AF+Alum in Infants Perinatally Exposed to HIV But Uninfected
HVTN316
A Partially Randomized Phase 1 Clinical Trial 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
2 other identifiers
interventional
22
1 country
1
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
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1 hiv-infections
Started Jul 2026
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 23, 2024
CompletedFirst Posted
Study publicly available on registry
September 26, 2024
CompletedStudy Start
First participant enrolled
July 13, 2026
ExpectedPrimary Completion
Last participant's last visit for primary outcome
June 3, 2027
Study Completion
Last participant's last visit for all outcomes
June 3, 2027
December 9, 2025
December 1, 2025
11 months
September 23, 2024
December 5, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (11)
Number of participants reporting local reactogenicity signs and symptoms and number of local reactogenicity signs and symptoms experienced by each participant
Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 \[March 2017\]
Measured through 14 days following receipt of study product at day 5, week 12, and week 28
Number of participants reporting systemic reactogenicity signs and symptoms symptoms and number of systemic reactogenicity signs and symptoms experienced by each participant,
Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 \[March 2017\]
Measured through 14 days following receipt of study product at day 5, week 12, and week 28
Number of participants reporting adverse events and overall number of adverse events
Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 \[March 2017\]
Measured through out the study period
Number of participants reporting serious adverse events and overall number of serious adverse events
Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 \[March 2017\]
Measured through 12 months post last vaccination at week 28
Number of participants reporting medically attended adverse events and overall number of medically attended adverse events
Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 \[March 2017\]
Measured through 12 months post last vaccination at week 28
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
Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 \[March 2017\]
Measured through 12 months post last vaccination at week 28
Number of participants reporting AEs leading to early participant withdrawal or permanent discontinuation
Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 \[March 2017\]
Measured through 12 months post last vaccination at week 28
Response rate of CD4bs-specific IgG binding antibodies
Measured by binding antibody multiplex assay (BAMA)
Measured 2 weeks after the 3rd vaccination at week 28
Magnitude of CD4bs-specific IgG binding antibodies
Measured by binding antibody multiplex assay (BAMA)
Measured 2 weeks after the 3rd vaccination at week 28
Response rate of CD4bs-specific memory B cells
Measured by flow cytometry
Measured 2 weeks after the 3rd vaccination at week 28
Magnitude of CD4bs-specific memory B cells
Measured by flow cytometry
Measured 2 weeks after the 3rd vaccination at week 28
Secondary Outcomes (13)
Response rate of serum Ab neutralization of vaccine-matched viruses
Measured 2 weeks after the 3rd vaccination at week 28
Magnitude of serum Ab neutralization of vaccine-matched viruses
Measured 2 weeks after the 3rd vaccination at week 28
Differential neutralization of HIV-1 strains that are diagnostic for CD4bs bNAb precursors
Measured 2 weeks after the 3rd vaccination at week 28
Response rate of serum Ab neutralization of heterologous HIV-1 strains
Measured 2 weeks after the 3rd vaccination at week 28
Magnitude of serum Ab neutralization of heterologous HIV-1 strains
Measured 2 weeks after the 3rd vaccination at week 28
- +8 more secondary outcomes
Study Arms (6)
Part A, Group 1: 426c.Mod.Core-C4b (20 mcg)
EXPERIMENTALParticipants will receive 426c.Mod.Core-C4b (20 mcg) alone to be administered as two 0.25-mL intramuscular (IM) doses, one into each thigh at weeks 0, 12, and 28.
Part A, Group 2: 426c.Mod.Core-C4b (20 mcg) + 3M-052-AF (0.3 mcg) + Alum (250 mcg)
EXPERIMENTALParticipants will receive 426c.Mod.Core-C4b (20 mcg) admixed with 3M-052-AF (0.3 mcg) and aluminum hydroxide suspension (Alum) (250 mcg) to be administered as two 0.25-mL IM doses, one into each thigh at weeks 0, 12, and 28.
Part A, Group 3: 426c.Mod.Core-C4b (20 mcg) + 3M-052-AF (0.75 mcg) + Alum (250 mcg)
EXPERIMENTALParticipants will receive 426c.Mod.Core-C4b (20 mcg) admixed with 3M-052-AF (0.75 mcg) and aluminum hydroxide suspension (Alum) (250 mcg) to be administered as two 0.25-mL IM doses, one into each thigh at weeks 0, 12, and 28.
Part A, Group 4: 426c.Mod.Core-C4b (20 mcg) + 3M-052-AF (1.5 mcg) + Alum (250 mcg)
EXPERIMENTALParticipants will receive 426c.Mod.Core-C4b (20 mcg) admixed with 3M-052-AF (1.5 mcg) and aluminum hydroxide suspension (Alum) (250 mcg) to be administered as two 0.25-mL IM doses, one into each thigh at weeks 0, 12, and 28.
Part B, Group 5: 426c.Mod.Core-C4b (20 mcg) + 3M-052-AF (TBD)* + Alum (250 mcg)
ACTIVE COMPARATORParticipants will receive 426c.Mod.Core-C4b (20 mcg) admixed with 3M-052-AF (TBD) and Alum (250 mcg) to be administered as two 0.25-mL IM doses, one into each thigh at weeks 0, 12, and 28.
Part B, Group 6: Placebo
PLACEBO COMPARATORParticipants will receive Placebo (Tris Sodium Chloride (NaCl) buffer ) to be administered as two 0.25-mL IM doses, one into each thigh at weeks 0, 12, and 28.
Interventions
self-assembling nanoparticle expressing up to 7 molecules of the 426c.Mod.Core envelope immunogen.
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
Aluminum hydroxide suspension (Alum) to be administered as 250 mcg (aluminum content) admixed with 426c.Mod.Core-C4b with 3M-052-AF.
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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)
- Estimated gestational age at birth is at least 37 weeks
- Note: If gestational age at birth is not documented in the infant's available birth records, study staff may assess gestational age at the earliest possible opportunity during the screening period and use this assessment for purposes of eligibility determination.
- Weight at birth is at least 2.5 kg
- Has initiated ARV prophylaxis consistent with current site-specific standard of care
- Hemoglobin (HgB) more than 14.0 g/dL
- White blood cell (WBC) count ≥ 7,000 cells/mm3
- Platelets more than 100,000 cells/mm3
- Alanine aminotransferase (ALT) less than 1.25 times upper limit of age-adjusted normal
- +7 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- HIV Vaccine Trials Networklead
- Fred Hutchinson Cancer Centercollaborator
- Access to Advanced Health Institutecollaborator
- National Institute of Allergy and Infectious Diseases (NIAID)collaborator
Study Sites (1)
Soweto HVTN CRS
Soweto, Gauteng, 1862, South Africa
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- STUDY CHAIR
Amy Violari
Perinatal HIV Research Unit
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Masking Details
- Part A will be open label.
- Purpose
- PREVENTION
- Intervention Model
- PARALLEL
- Sponsor Type
- NETWORK
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 23, 2024
First Posted
September 26, 2024
Study Start (Estimated)
July 13, 2026
Primary Completion (Estimated)
June 3, 2027
Study Completion (Estimated)
June 3, 2027
Last Updated
December 9, 2025
Record last verified: 2025-12