Safety and Immunogenicity of Chimeric Hemagglutinin mRNA Vaccine Candidates
A Phase 1, Randomized, Controlled, Dose-Ranging Study to Evaluate the Safety and Immunogenicity of Influenza A Group 1 and Influenza A Group 2 mRNA Chimeric Hemagglutinin Vaccine Candidates Alone and in Combination in Healthy Adults.
2 other identifiers
interventional
60
1 country
1
Brief Summary
This is a Phase 1, randomized, controlled, dose-ranging clinical trial to assess the safety and immunogenicity of novel influenza A Group 1 and influenza A Group 2 mRNA chimeric hemagglutinin (HA) vaccine candidates given as intramuscular injections alone and in combination. A total of 60 healthy men and non-pregnant, non-breastfeeding women aged 18 through 59 years will be enrolled in one of 6 study arms. The 6 arms will consist of: 1) Sequential influenza A Group 1 mRNA chimeric hemagglutinin: cH8/1 (25 µg) followed by cH5/1 (25 µg), 2) Sequential influenza A Group 2 mRNA chimeric hemagglutinin: cH15/3 (25 µg) followed by cH4/3 (25 µg), 3) Sequential combined influenza A Group 1 and Group 2 mRNA chimeric hemagglutinin: cH8/1 + cH15/3 (25 µg) followed by cH5/1 + cH4/3 (25 µg), 4) A single dose of combined influenza A Group 1 and Group 2 mRNA chimeric hemagglutinin: cH8/1 + cH15/3 (50 µg) followed by placebo, 5) A single dose of combined influenza A Group 1 and Group 2 mRNA chimeric hemagglutinin: cH5/1 + cH4/3 (50 µg) followed by placebo, 6) Sequential combined influenza A Group 1 and Group 2 mRNA chimeric hemagglutinin: cH8/1 + cH15/3 (50 µg) followed by cH5/1 + cH4/3 (50 µg). The primary objectives are to evaluate safety and immunogenicity: 1) To assess the safety and reactogenicity of one or two doses of monovalent or bivalent Group 1 and 2 study products and 2) To describe the Group 1 and 2 anti-HA stalk IgG antibody responses of one or two doses of monovalent or bivalent Group 1 and 2 study products by ELISA.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
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
July 9, 2026
CompletedFirst Posted
Study publicly available on registry
July 14, 2026
CompletedStudy Start
First participant enrolled
July 17, 2026
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 12, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
April 12, 2027
July 31, 2026
July 8, 2026
9 months
July 9, 2026
July 30, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (13)
Geometric mean fold rise (GMFR) from baseline in HA-stalk specific titers by ELISA
Day 1 through Day 85
Geometric mean titer (GMT) by ELISA
Day 1 Through Day 85
Number and percentage of participants with greater than or equal to a 2-, 4-, and 10-fold rise from baseline in Hemagglutinin (HA)-stalk specific titers by ELISA
Day1 through Day 85
Occurrence of Adverse Events of Special Interest (AESIs)
Day 1 through Day 240
Occurrence of Guillain-Barre Syndrome (GBS)
Through Day 240
Occurrence of hematological or biochemical laboratory adverse events
Day 8 through Day 64
Occurrence of laboratory confirmed influenza A infection
Through Day 240
Occurrence of Medically-Attended Adverse Events (MAAEs)
Through Day 240
Occurrence of New-Onset Chronic Medical Conditions (NOCMCs)
Through Day 240
Occurrence of Serious Adverse Events (SAEs)
Through Day 240
Occurrence of solicited local adverse events (AEs)
Day 1 through Day 64
Occurrence of solicited systemic adverse events (AEs)
Day 1 through Day 64
Occurrence of unsolicited adverse events (AEs)
Day 1 through Day 85
Secondary Outcomes (3)
Geometric mean fold-rise (GMFR) from baseline in Hemagglutinin (HA) stalk specific titers by ELISA
Day 240
Hemagglutinin (HA)-stalk specific geometric mean titer (GMT) by ELISA
Day 240
Number and percentage of participants with greater than or equal to a 2-, 4-, and 10-fold rise from baseline in Hemagglutinin (HA) -stalk specific titers by ELISA
Day 240
Study Arms (6)
Cohort 1, Arm1
EXPERIMENTALHealthy adults will receive 2 monovalent dose intramuscular injections. cH8/1 (25ug) chimeric Hemagglutinin (HA) is the first dose given on Day 1, followed by a second dose administered 57 days later with cH5 /1(25 ug). N = 10
Cohort 1, Arm2
EXPERIMENTALHealthy adults will receive 2 monovalent dose intramuscular injections. cH15/3 (25ug) chimeric HA is the first dose given on Day 1, followed by a second dose of cH4/3 (25ug), administered 57 days later. N = 10.
Cohort 1, Arm3
EXPERIMENTALHealthy adults will receive 2 low dose bivalent intramuscular injections. cH8/1(12.5ug) + cH15/3 (12.5ug) chimeric HA is the first dose given on Day 1, followed by a second dose of cH5/1 (12.5ug) + cH4/3(12.5 ug) administered 57 days later. N = 10.
Cohort 2, Arm4
EXPERIMENTALHealthy adults will receive a single high dose bivalent combination intramuscular injection along with a placebo dose. cH8/1(25ug) + cH15/3(25ug) will be administered on Day 1, followed by a placebo dose 57 days later. N = 10.
Cohort 2, Arm5
EXPERIMENTALHealthy adults will receive a single high dose bivalent combination intramuscular injection along with a placebo dose. cH5/1(25ug) + cH4/3(25ug) will be administered on Day 1, followed by a placebo dose 57 days later. N = 10.
Cohort 2, Arm6
EXPERIMENTALHealthy adults will receive 2 high dose bivalent intramuscular injections. cH8/1(25ug) + cH15/3 (25ug) is the first dose given on Day 1, followed by the second dose of cH5/1(25 ug) + cH4/3 (25 ug) administered 57 days later. N = 10.
Interventions
The cH15/3 RNA study product encodes for a novel chimeric hemagglutinin comprised of an H15 HA head domain derived from influenza A/wedge-tailed shearwater/Western Australia/2576/1979 (H15N9) and the conserved stem domain derived from influenza A/Hong Kong/2014 (H3N2) (GenBank: OQ349633). The cH15/3 RNA is encapsulated in LNPs for delivery. The LNP is comprised of 4 lipid components: ionizable lipid (ALC-0315), distearoylphosphatidylcholine (DSPC), cholesterol (non-animal derived), and PEG lipid (ALC-0159).
The cH4/3 RNA encodes a novel chimeric hemagglutinin comprised of an H4 head domain from A/duck/Czechoslovakia/1956 (H4N6) and a conserved stem domain from A/Hong Kong/2014 (H3N2) (GenBank: OQ349617), delivered via lipid nanoparticles (LNPs) containing ionizable lipid (ALC-0315), distearoylphosphatidylcholine (DSPC), cholesterol (non-animal derived), and PEG lipid (ALC-0159).
cH5/1N1 is a H1N1 influenza vaccine: egg grown split inactivated influenza virus vaccines containing chimeric hemagglutinins (HAs). The chimeric viruses contain the globular heads of exotic viruses- and the HA stem domain and neuraminidase protein from currently circulating seasonal H1N1.
cH8/1N1 is a H1N1 influenza vaccine: egg grown split inactivated influenza virus vaccines containing chimeric hemagglutinins (HAs). The chimeric viruses contain the globular heads of exotic viruses- and the HA stem domain and neuraminidase protein from currently circulating seasonal H1N1.
Eligibility Criteria
You may qualify if:
- Provision of signed and dated informed consent form before the initiation of any study procedures.
- Stated willingness to comply with all study procedures and availability for the duration of the study.
- Non-pregnant healthy adults, aged 18 to 59 years of age, inclusive, at the time of enrollment.
- In good general health as evidenced by medical history or diagnosed with stable chronic medical or psychiatric diagnoses or conditions.\*
You may not qualify if:
- Oral temperature is less than 100.4 degrees Fahrenheit\*.
- Heart rate (HR) is 55 to 100 beats per minute, inclusive\*. \*Screening heart rate values in the normal range or with grade 1 abnormalities deemed not clinically significant by the site PI or designated clinician licensed to make medical diagnoses and listed on Form FDA 1572 are considered acceptable.
- Systolic blood pressure is 90 to 140 mmHg, inclusive\*.
- \*Screening systolic blood pressure values in the normal range or with grade 1 abnormalities deemed not clinically significant by the site PI or designated clinician licensed to make medical diagnoses and listed on Form FDA 1572 are considered acceptable.
- Diastolic blood pressure is 55 to 90 mmHg, inclusive\*. \*Screening diastolic blood pressure values in the normal range or with grade 1 abnormalities deemed not clinically significant by the site PI or designated clinician licensed to make medical diagnoses and listed on Form FDA 1572 are considered acceptable.
- BMI between 18 kilograms/square meter (kg/m\^2) (inclusive) and \<35 kg/m\^2 at screening
- Females of childbearing potential\* must agree to true abstinence\*\* or use at least 1 acceptable primary form of contraception\*\*\*,\*\*\*\*
- Not of childbearing 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 the 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 for at least 30 days before screening and agreement to use such a method during study participation and for an additional 30 days after the end of last study product administration.
- Females of reproductive potential must have a negative serum pregnancy test at screening and a negative urine pregnancy test within 24 hours before the study product administration.
- Must agree to have samples collected for secondary research.
- A history of any medical disease or condition that, in the opinion of the site PI or appropriate sub-investigator, is a contraindication to study participation\*.
- \*Including acute, subacute, intermittent, or chronic medical disease or condition that would place the participant at an unacceptable risk of injury, render the participant unable to meet the requirements of the protocol, or may interfere with the evaluation of responses or the participant's successful completion of this trial.
- +36 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
University of Maryland, School of Medicine, Center for Vaccine Development and Global Health
Baltimore, Maryland, 21201-1509, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- PREVENTION
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 9, 2026
First Posted
July 14, 2026
Study Start
July 17, 2026
Primary Completion (Estimated)
April 12, 2027
Study Completion (Estimated)
April 12, 2027
Last Updated
July 31, 2026
Record last verified: 2026-07-08