A Phase 1 Study to Evaluate the Safety and Immunogenicity of Two Doses of a Novel H5 Antigenically Central (AC)-Anhui mRNA-LNP Vaccine in Healthy Adults
This is a phase 1, multicenter, randomized, double-blind trial of two influenza A/H5 mRNA-based vaccines on healthy adult participants, 18-49 years of age. Stage 1 will serve as the open-label, dose finding stage. The first 10 participants will receive 12.5 mcg of H5 AC-Anhui RNA vaccine (Group 1), and the second 10 participants will receive 25 mcg of H5 AC-Anhui RNA vaccine (Group 2). After Protocol Safety Review Team (PSRT) review of reactogenicity and safety data through Day 8 for both Groups 1 and 2, another 10 participants may be enrolled to receive 50 mcg of H5 AC-Anhui RNA vaccine (Group 3). Safety data from 7 days after dose 2 for Groups 1 and 2 participants will be reviewed by the PSRT prior to clearing Group 3 participants for the second dose of vaccine. Individual participants will be followed for approximately 6 months following the second dose of vaccine. The primary objective is to assess the safety of two doses of H5 AC-Anhui RNA vaccine or H5-Astrakhan RNA vaccine administered intramuscularly in healthy adults (18-49 years). Once the Day 36 data from Group 3 are reviewed by the PSRT, a dose will be chosen (12.5 mcg, 25 mcg, or 50 mcg) for advancement to Stage 2 where 50 participants will be randomized 1:1 to receive either H5 AC-Anhui RNA (Group 4) or H5 Astrakhan RNA (Group 5) in a double-blinded manner.
• Provides written informed consent prior to the initiation of any trial procedures
• Can understand and agrees to comply with all planned trial procedures and be available for all study visits
• Adult volunteers, age 18-49 years, inclusive, at time of enrollment.
• In good general health.\* \* Good health is defined by the absence of a medical condition described in the exclusion criteria. If the participant has another current, ongoing medical condition, the condition cannot meet any of the following criteria:
‣ was first diagnosed within 3 months of enrollment with a clinically significant condition, in the opinion of investigator
⁃ had non-elective surgery, clinically significant medical procedure, or hospitalization within 3 months of enrollment;
⁃ received new prescription for systemic medication within 30 days of enrollment, unless the new prescription is in the same class of agent or a transition from generic to/from brand name equivalent; or
⁃ takes medication that may pose a risk to participant's safety or impede assessment of adverse events or study endpoints if they participate in the study.
• Participants of childbearing potential\* must agree to use or have practiced true abstinence\*\* or use at least one acceptable primary form of contraception.\*\*\* \*These criteria apply to females who are in a heterosexual relationship who are of childbearing potential. Participants not of childbearing potential include 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, tubal ligation/salpingectomy, or permanently implanted contraceptive device placement).
• \*\*True abstinence is complete lack of penile-vaginal intercourse. Periodic abstinence \[e.g., calendar, ovulation, symptothermal, post-ovulation methods\] and withdrawal are not acceptable methods.
• \*\*\*Acceptable forms of primary contraception include monogamous relationship with a vasectomized partner who has been vasectomized for 180 days or more prior to the participant's vaccination; intrauterine devices; birth control pills; and injectable/implantable/insertable/transdermal hormonal birth control products. Participants must have used \>/=1 acceptable primary form of contraception for at least 30 days prior to vaccination and agree to continue \>/=1 acceptable primary form of contraception through 60 days after last vaccination.
• Must agree to refrain from donating blood or blood products during the first 6 months of the study
• Body mass index (BMI) 18 kg/m\^2 to 35 kg/m\^2, inclusive, and a weight of 130 kg or less at the time of screening