A Phase 1 interventional study of H5 AC-Anhui RNA Vaccine and H5 Astrakhan RNA Vaccine in Avian Influenza, sponsored by National Institute of Allergy and Infectious Diseases (NIAID). Completed at 3 sites in United States. Open to participants aged 18 Years to 49 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-06-12.
Sponsored by National Institute of Allergy and Infectious Diseases (NIAID) · Phase 1, Interventional, and Prevention
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.
This is a multicenter, randomized, double-blind trial of two influenza A/H5 mRNA-based vaccines. The trial population consists of 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). These groups will be enrolled sequentially without pause unless study halting rules are triggered. 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 Day 36 (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. 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. Participants will be randomized on the day of enrollment. Screening and enrollment can occur on the same day. 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). The secondary objective is to assess the serum antibody responses to H5 AC-Anhui RNA vaccine or H5-Astrakhan RNA vaccine.
113 studies on the registry are indexed under Influenza in Birds; 3 are open to participants now.
This study's enrollment of 80 is below the median of 157 across 103 interventional studies indexed under Influenza in Birds.
Browse Influenza in Birds studies →National Institute of Allergy and Infectious Diseases (NIAID) is the lead sponsor of 2,401 studies on the registry; 179 are open to participants now.
Of its 396 completed or terminated interventional studies of FDA-regulated products, 294 (74%) have results posted.
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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:
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.
Exclusion Criteria:
Has a history of anaphylaxis to any drug compound, vaccine, food, or other substance, unless approved by the Investigator (or designee)**
**Sensitivity to components of the study product is exclusionary.
Has used any prohibited medication within 30 days prior to Day 1 or plans to use prohibited medications*** through Day 57
***Prohibited medications include systemic immunosuppressive drugs, immune modulators (except acetaminophen or non-steroidal anti-inflammatory drugs), oral corticosteroids, and systemic antineoplastic agents. Topical, inhaled, and intranasal steroids, as well as topical anti-neoplastic agents are acceptable
Abnormal blood pressure or temperature (Grade 1 or higher) at time of vaccination
****Grade 1 or higher is equivalent to: Systolic blood pressure (SBP) > 140 mmHg or \< 90 mmHg Diastolic blood pressure (DBP) > 90 mmHg Oral temperature >/= 38.0 degrees Celsius (100.4 degrees Fahrenheit)
Healthy male and non-pregnant female participants, ages 18 to 49, will be administered two intramuscular doses of H5 Antigenically Central (AC)-Anhui RNA Vaccine at 12.5 mcg on days 1 and 29. N=10
Biological: H5 AC-Anhui RNA Vaccine · Other: Sodium Chloride, 0.9%
Healthy male and non-pregnant female participants, ages 18 to 49, will be administered two intramuscular doses of H5 AC-Anhui RNA Vaccine at 25 mcg on days 1 and 29. N=10
Biological: H5 AC-Anhui RNA Vaccine · Other: Sodium Chloride, 0.9%
After the Protocol Safety Review Team (PSRT) reviews the reactogenicity and safety data, through Day 8, for both Stage 1 Group 1 and Stage 1 Group 2, healthy male and non-pregnant female participants, ages 18 to 49, will be administered two intramuscular doses of H5 AC-Anhui RNA Vaccine at 50 mcg on days 1 and 29. N=10
Biological: H5 AC-Anhui RNA Vaccine · Other: Sodium Chloride, 0.9%
Following the Day 36 Stage 1 Group 3 data review by the Protocol Safety Review Team (PSRT), healthy male and non-pregnant female participants, ages 18 to 49, will be administered two intramuscular doses of H5 AC-Anhui RNA Vaccine at 25 mcg on days 1 and 29. N=25
Biological: H5 AC-Anhui RNA Vaccine · Other: Sodium Chloride, 0.9%
Following the Day 36 Stage 1 Group 3 data review by the Protocol Safety Review Team (PSRT), healthy male and non-pregnant female participants, ages 18 to 49, will be administered two intramuscular doses of H5 Astrakhan RNA Vaccine at 25 mcg on days 1 and 29. N=25
Biological: H5 Astrakhan RNA Vaccine · Other: Sodium Chloride, 0.9%
A nucleoside-modified mRNA vaccine encoding a stabilized, antigenically central hemagglutinin (HA) from influenza A(H5), based on A/Anhui/1/2005 (clade 2.3.4) with substitutions 222QL, 224GS, 156TA, and 134TA. The 2119-nt mRNA is encapsulated in lipid nanoparticles (LNPs) for intramuscular delivery.
The vaccine product consists of a monovalent nucleoside-modified mRNA that encodes a traditionally selected avian influenza HA. The H5 Astrakhan RNA encodes the HA from the clade 2.3.4.4b A/Astrakhan/3212/2020 virus.
0.9% Sodium Chloride Injection
Number and Percentage of participants experiencing any adverse events of special interest (AESI)
Time frame: Through 90 days after second vaccination
Number and Percentage of participants experiencing any medically attended adverse events (MAAE)
Time frame: Through 6 months following the second dose
Number and Percentage of participants experiencing any non-serious unsolicited adverse events (AEs)
Time frame: Through 28 days following each dose
Number and Percentage of participants experiencing any serious adverse events (SAE)
Time frame: Through 6 months following the second dose
Number and Percentage of participants experiencing new-onset chronic medical conditions (NOCMC)
Time frame: Through 6 months following the second dose
Number and Percentage of participants experiencing solicited local reactogenicity adverse events (AEs)
Time frame: Through 7 days following each dose
Number and Percentage of participants experiencing solicited systemic reactogenicity adverse events (AEs)
Time frame: Through 7 days following each dose
Number and Percentage of participants with clinical laboratory adverse events (AEs)
Time frame: Through 7 days following each dose
Geometric mean fold rise (GMFR) in Group 1-specific anti-stalk serum antibodies since pre-vaccination (Day 1)
Time frame: Day 8 through Day 57
Geometric mean fold rise (GMFR) in homologous and heterologous H5-specific Neut antibody since pre-vaccination (Day 1)
Time frame: Day 8 through Day 57
Geometric mean fold rise in homologous and heterologous H5-specific Hemagglutination Inhibition Antibody (HAI) antibody since pre-vaccination
Time frame: Day 8 through Day 57
Geometric mean titers of Group 1-specific anti-stalk serum antibodies
Time frame: Day 1 through Day 57
Geometric mean titers of homologous and heterologous H5-specific hemagglutinin inhibition (HAI) antibodies
Time frame: Day 1 through Day 57
Geometric mean titers of homologous and heterologous H5-specific neutralizing antibodies (Neut)
Time frame: Day 1 through Day 57
Number and Percentage of participants achieving Hemagglutination Inhibition Antibody (HAI) titer seroconversion since pre-vaccination (Day 1) against the homologous and heterologous H5-specific hemagglutinin
Seroconversion is defined as either a pre-vaccination titer \<1:10 and a post-vaccination titer \>/=1:40 or a pre- vaccination titer \>/=1:10 and a minimum four-fold rise in post-vaccination antibody titer
Time frame: Day 8 through Day 57
Number and Percentage of participants demonstrating Hemagglutination Inhibition Antibody (HAI) titer seroprotection against homologous and heterologous H5-specific hemagglutinin
Seroprotection defined as \>/=1:40 titer
Time frame: Day 1 through Day 57
The number and percentage of participants achieving Neut seroconversion since pre-vaccination (Day 1) against the homologous and heterologous H5-specific hemagglutinin
Seroconversion is defined as either a pre-vaccination titer \<1:10 and a post-vaccination titer \>/= 1:40 or a pre-vaccination titer \>/= 1:10 and a minimum four-fold rise in post-vaccination antibody titer
Time frame: Day 8 through Day 57
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National Institute of Allergy and Infectious Diseases (NIAID)