A Study to Evaluate the Safety and Immunogenicity of a Single Dose of H1ssF-3928 mRNA-LNP in Healthy Adults
A Phase 1, Open-Label, Comparator-Controlled, Dose-Escalation Study to Evaluate the Safety and Immunogenicity of a Single Dose of VRC H1ssF-3928 mRNA-LNP in Healthy Adults
2 other identifiers
interventional
50
1 country
1
Brief Summary
This is a Phase 1, single-site, open-label, comparator-controlled dose escalating study of an intramuscularly (IM) administered mRNA-LNP vaccine encoding for (Vaccine Research Center) VRC H1ssF 3928 of up to 50 healthy adult volunteers aged 18 to 49 years, inclusive. This study is designed to assess the safety and immunogenicity of one dose of H1ssF 3928 mRNA Vaccine. Eligible participants will be sequentially enrolled into dosing groups (10 mcg, 25 mcg, and 50 mcg, selected optimal dose) to receive the H1ssF 3928 mRNA Vaccine at the specified dose. A separate group of 10 participants will receive licensed quadrivalent influenza vaccine (IIV4). Subjects receiving IIV4 will be followed for safety but only their immune responses will be compared to those of participants receiving H1ssF 3928 mRNA Vaccine. Dosing of H1ssF 3928 mRNA Vaccine will commence at the lowest dose (10 mcg) and only escalate to the next highest dose if safety concerns are not identified. Up to ten subjects will be enrolled per dosing cohort. Reactogenicity and adverse event (AE) information through Day 7 and clinical laboratory results through Day 8 from the first three dosing groups will guide the selection of an optimal dose group to include 10 subjects who will receive the optimal dose of mRNA-LNP. The primary objective of this study is to assess the safety of a single dose of VRC H1ssF 3928 mRNA-LNP vaccine administered IM in healthy adults, 18-49 yrs, at doses of 10 mcg, 25 mcg, and 50 mcg.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Apr 2023
Typical duration for phase_1
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
February 23, 2023
CompletedFirst Posted
Study publicly available on registry
March 6, 2023
CompletedStudy Start
First participant enrolled
April 5, 2023
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 3, 2025
CompletedStudy Completion
Last participant's last visit for all outcomes
October 3, 2025
CompletedOctober 31, 2025
June 23, 2023
2.5 years
February 23, 2023
October 30, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (9)
Occurrence of adverse events of special interest (AESIs) corresponding to myocarditis, pericarditis, or myopericarditis with VRC H1ssF_3928 mRNA-LNP vaccine
Day 1 through Day 57
Occurrence of any adverse events of special interest (AESIs) with VRC H1ssF_3928 mRNA-LNP vaccine.
adverse events of special interest (AESIs) corresponding to Grade 2 or greater decrease in lymphocyte or neutrophil count
Day 1 through Day 366
Occurrence of any influenza-like illnesses (ILIs) with VRC H1ssF_3928 mRNA-LNP vaccine.
Day 1 through Day 366
Occurrence of any new-onset chronic medical conditions (NOCMCs) with VRC H1ssF_3928 mRNA-LNP vaccine.
Day 1 through Day 366
Occurrence of any serious adverse events (SAEs) with VRC H1ssF_3928 mRNA-LNP vaccine.
Day 1 through Day 366
Occurrence of any unsolicited adverse events (AEs) with VRC H1ssF_3928 mRNA-LNP vaccine.
Day 1 through Day 28
Occurrence of clinical laboratory adverse events (AEs) with VRC H1ssF_3928 mRNA-LNP vaccine.
Day 1 through Day 57
Occurrence of medically attended adverse events (MAAEs) with VRC H1ssF_3928 mRNA-LNP vaccine.
Day 1 through Day 366
Occurrence of solicited reactogenicity adverse events (AEs) with VRC H1ssF_3928 mRNA-LNP vaccine.
Both local and systemic adverse events will be assessed
Day 1 through Day 14
Secondary Outcomes (6)
Geometric mean fold rise (GMFR) of anti-stalk serum antibodies measured by enzyme linked immunosorbent assay (ELISA).
Day 1 through Day 57
Geometric mean fold rise (GMFR) of homologous H1-specific neutralizing antibodies in a reporter microneutralization assay.
Day 1 through Day 57
Geometric mean fold rise (GMFR) of homologous H1-specific neutralizing antibodies in a viral microneutralization assay.
Day 1 through Day 57
Geometric mean titers (GMT) of homologous H1-specific neutralizing antibodies in a reporter microneutralization assay.
Day 1 through Day 57
Geometric mean titers (GMT) Of homologous H1-specific neutralizing antibodies in a viral microneutralization assay.
Day 1 through Day 57
- +1 more secondary outcomes
Study Arms (5)
Arm 1, Low Dose
EXPERIMENTAL10 healthy adult volunteer subjects from 18-49 years of age are split into two subgroups. The sentinel subgroup includes 2 vaccine recipients who will receive 10 mcg of the H1ssF\_3928 mRNA Vaccine, administered intramuscularly once. The sentinel subgroup is observed for 8 days to monitor any early vaccine related adverse events. After the observation period, the remaining participants will receive the same dosage, 10 mcg of the H1ssF 3928 mRNA vaccine administered intramuscularly once. N = 10
Arm 2, Medium Dose
EXPERIMENTAL10 healthy adult volunteer subjects from 18-49 years of age are split into two subgroups. The sentinel subgroup includes 2 vaccine recipients who will receive 25 mcg of the H1ssF\_3928 mRNA Vaccine, administered intramuscularly once. The sentinel subgroup is observed for 8 days to monitor any early vaccine related adverse events. After the observation period, the remaining participants will receive the same dosage, 25 mcg of the H1ssF 3928 mRNA vaccine administered intramuscularly once. N = 10
Arm 3, High Dose
EXPERIMENTAL10 healthy adult volunteer subjects from 18-49 years of age are split into two subgroups. The sentinel subgroup includes 2 vaccine recipients who will receive 50 mcg of the H1ssF\_3928 mRNA Vaccine, administered intramuscularly once. The sentinel subgroup is observed for 8 days to monitor any early vaccine related adverse events. After the observation period, the remaining participants will receive the same dosage, 50 mcg of the H1ssF 3928 mRNA vaccine administered intramuscularly once. N = 10
Arm 4, Optimal Dose
EXPERIMENTAL10 healthy adult volunteer subjects from 18-49 years of age will receive the selected optimal dose of the H1ssF\_3928 mRNA Vaccine, administered intramuscularly once. The optimal dosing group will be selected based on safety outcomes from the 10 mcg, 25 mcg, and 50 mcg dosing groups. For the optimal dose, the highest dose with no identified safety concerns as determined by the Safety Review Committee (SRC) will be selected. N =10
Arm 5, IIV4
ACTIVE COMPARATOR10 healthy adult volunteer subjects from 18-49 years of age will receive licensed Quadrivalent Influenza Vaccine (IIV4), administered intramuscularly once. Subjects receiving IIV4 will be followed for safety, but only their immune responses will be compared to those of participants receiving H1ssF\_3928 mRNA Vaccine. N=10
Interventions
A seasonal quadrivalent inactivated influenza vaccine (IIV4), prepared from influenza viruses propagated in embryonated chicken eggs, protecting against 2 influenza A subtypes and 2 influenza B subtypes.
0.9% Sodium Chloride Injection
The vaccine consists of modified nucleoside messenger RNA (mRNA) encapsulated in lipid nanoparticles (LNP), comprised of four lipid components: (ALC-307 (ionizable lipid), DSPC, cholesterol, and ALC-0159 \[PEG lipid\]).
Eligibility Criteria
You may qualify if:
- Provide written informed consent prior to initiation of any study procedure.
- Are able to understand and comply with planned study procedures and be available for all study visits.
- Are males or non-pregnant, non-breastfeeding females, 18 to 49 years of age, inclusive at time of screening and enrollment.
- Must agree to collection of venous blood and nasal absorption specimens per protocol and enrollment in DMID Protocol No. 19-0025 biorepository protocol for secondary research and use of residual biologic specimens.
You may not qualify if:
- Does not have an ongoing symptomatic condition\* for which subject has had or has ongoing medical investigations but has not yet received a diagnosis or treatment plan.
- \*e.g., ongoing fatigue without a diagnosis for symptom.
- Pulse is 50 to 100 beats per minute, inclusive.
- Systolic blood pressure is 90 to 140 mmHg, inclusive.
- Diastolic blood pressure is 55 to 90 mmHg, inclusive.
- Body mass index (BMI) of 18 kilograms/square meter (kg/m\^2) (inclusive) to \<35 kg/m\^2 at screening
- Women of childbearing potential\* must agree to use or have practiced true abstinence\*\* or use at least 1 acceptable primary form of contraception.\*\*\*
- \*Not of child bearing potential - post-menopausal females (defined as having a history of amenorrhea for at least one year) or a documented status as being surgically sterile (hysterectomy, bilateral oophorectomy, salpingectomy, or Essure placement with history of documented radiological confirmation test at least 90 days after the procedure).
- \*\*True abstinence is 100% of time no sexual intercourse (male's penis enters the female's vagina). (Periodic abstinence \[e.g. calendar, ovulation, symptothermal, post-ovulation methods\] and withdrawal are not acceptable methods of contraception).
- Acceptable forms of primary contraception include monogamous relationship with a vasectomized partner who has been vasectomized for 180 days or more prior to the subject receiving the study product, tubal ligation, intrauterine devices, birth control pills, and injectable/implantable/insertable hormonal birth control products.
- Must use at least one acceptable primary form of contraception or true abstinence for at least 30 days prior to receipt of study product and at least one acceptable primary form of contraception or true abstinence for at least 30 days following receipt of study product.
- Women of childbearing potential must have a negative serum HCG pregnancy test at screening and a negative urine HCG pregnancy test within 24 hours prior to the study vaccination.
- Male participants receiving VRC H1ssF\_3928 mRNA-LNP must agree to refrain from donating sperm and to use contraception until Day 60 after vaccination.\*
- Acceptable contraception includes abstinence from intercourse with a female of childbearing potential or use of a male condom when engaging in any activity that allows for passage of ejaculate to a female during the intervention period for at least 60 days after study vaccination.
- Males in the immunogenicity comparator group do not have to refrain from sperm donation or abstain from intercourse or agree to use a male condom for purposes of this study.
- +47 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Duke Vaccine and Trials Unit
Durham, North Carolina, 27704, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- PREVENTION
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 23, 2023
First Posted
March 6, 2023
Study Start
April 5, 2023
Primary Completion
October 3, 2025
Study Completion
October 3, 2025
Last Updated
October 31, 2025
Record last verified: 2023-06-23