Influenza
Conditions
Keywords
cH15/3 (WA79/HK14), cH4/3 (CZ56/HK14), cH5/1 (VN04/CA09), cH8/1 (SW02/CA09), Chimeric Hemagglutinin, Double Blinded, Flu-CHAMPs, Healthy adults, Immunogenicity, Influenza, Influenza A, mRNA, Phase 1, Placebo, Randomized, Safety, Vaccine
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.
Detailed description
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. The secondary objective is to describe the Group 1 and Group 2 anti-hemagglutinin stalk Immunoglobulin G (IgG) antibody response of one or two doses of monovalent or bivalent Group 1 and 2 study products by ELISA at a later timepoints.
Interventions
BIOLOGICALcH15/3
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).
BIOLOGICALcH4/3
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).
BIOLOGICALcH5/1N1
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.
BIOLOGICALcH8/1N1
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.
DRUGSaline
Sodium chloride solution.
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 59 Years
Healthy volunteers
Yes
Inclusion criteria
1. Provision of signed and dated informed consent form before the initiation of any study procedures. 2. Stated willingness to comply with all study procedures and availability for the duration of the study. 3. Non-pregnant healthy adults, aged 18 to 59 years of age, inclusive, at the time of enrollment. 4. In good general health as evidenced by medical history or diagnosed with stable chronic medical or psychiatric diagnoses or conditions.\* \*As determined by medical history, medications use, and physical examination to evaluate ongoing chronic medical or psychiatric diagnoses or conditions, defined as those that have been present for at least 90 days, which would not affect the assessment of the safety of participants or the immunogenicity of study products. These medical diagnoses or conditions should be stable for the last 60 days (no hospitalizations, emergency room \[ER\] or urgent care for the condition \[excluding musculoskeletal conditions\], or invasive medical procedure and no adverse symptoms that need medical intervention such as medication change/supplemental oxygen). This includes no change in chronic prescription medication or dose as a result of new symptoms or deterioration of the condition or disease being treated in the 30 days prior to enrollment. Any prescription change that is due to a change of health care provider, insurance company, etc., or that is done for financial reasons, as long as in the same class of medication, will not be considered a deviation of this inclusion criterion. Participants may be on chronic or as-needed (prn) medications if, in the opinion of the site PI or appropriate sub-investigator, they pose no additional risk to participant safety or assessment of reactogenicity and immunogenicity, and do not indicate a worsening or treatment of continued symptoms of medical diagnosis or condition. Note: Low-dose topical corticosteroids as outlined in the
Exclusion criteria
as well as herbals, vitamins, and supplements are permitted. 5. Oral temperature is less than 100.4 degrees Fahrenheit\*. \*Inclusion requirement at enrollment and prior to study product administration. 6. 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. 7. 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. 8. 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. 9. BMI between 18 kilograms/square meter (kg/m\^2) (inclusive) and \<35 kg/m\^2 at screening 10. 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. 11. 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. 12. Must agree to have samples collected for secondary research.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame |
|---|---|
| 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 |
Countries
United States
Contacts
CONTACTMeagan Deming
Outcome results
None listed