A Study to Evaluate the Safety and Immunogenicity of Two Doses of a Novel H5 Central Antigen mRNA-LNP in Healthy Adults

NCT07019883 | Active Not Recruiting Phase 1 FDA Drug

• 1 other identifier: 24-0024
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Avian Influenza

Keywords

H5N1; Healthy Adults; Influenza; Novel H5 Central Antigen mRNA-LNP; Phase 1; Safety and Immunogenicity; Vaccine

Outcome Measures

Primary Outcomes (8)

• Number and Percentage of participants experiencing any adverse events of special interest (AESI)

  Through 90 days after second vaccination

• Number and Percentage of participants experiencing any medically attended adverse events (MAAE)

  Through 6 months following the second dose

• Number and Percentage of participants experiencing any non-serious unsolicited adverse events (AEs)

  Through 28 days following each dose

• Number and Percentage of participants experiencing any serious adverse events (SAE)

  Through 6 months following the second dose

• Number and Percentage of participants experiencing new-onset chronic medical conditions (NOCMC)

  Through 6 months following the second dose

• Number and Percentage of participants experiencing solicited local reactogenicity adverse events (AEs)

  Through 7 days following each dose

• Number and Percentage of participants experiencing solicited systemic reactogenicity adverse events (AEs)

  Through 7 days following each dose

• Number and Percentage of participants with clinical laboratory adverse events (AEs)

  Through 7 days following each dose

Secondary Outcomes (9)

• Geometric mean fold rise (GMFR) in Group 1-specific anti-stalk serum antibodies since pre-vaccination (Day 1)

  Day 8 through Day 57

• Geometric mean fold rise (GMFR) in homologous and heterologous H5-specific Neut antibody since pre-vaccination (Day 1)

  Day 8 through Day 57

• Geometric mean fold rise in homologous and heterologous H5-specific Hemagglutination Inhibition Antibody (HAI) antibody since pre-vaccination

  Day 8 through Day 57

• Geometric mean titers of Group 1-specific anti-stalk serum antibodies

  Day 1 through Day 57

• Geometric mean titers of homologous and heterologous H5-specific hemagglutinin inhibition (HAI) antibodies

  Day 1 through Day 57

Study Arms (5)

Stage 1 Group 1

EXPERIMENTAL

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%

Stage 1 Group 2

EXPERIMENTAL

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%

Stage 1 Group 3

EXPERIMENTAL

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%

Stage 2 Group 4

EXPERIMENTAL

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%

Stage 2 Group 5

EXPERIMENTAL

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%

Interventions

H5 AC-Anhui RNA Vaccine BIOLOGICAL

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.

Stage 1 Group 1; Stage 1 Group 2; Stage 1 Group 3; Stage 2 Group 4

H5 Astrakhan RNA Vaccine BIOLOGICAL

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.

Stage 2 Group 5

Sodium Chloride, 0.9% OTHER

0.9% Sodium Chloride Injection

Stage 1 Group 1; Stage 1 Group 2; Stage 1 Group 3; Stage 2 Group 4; Stage 2 Group 5

Eligibility Criteria

• Age: 18 Years - 49 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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
• Positive pregnancy test at screening or prior to vaccine dose
• Participant who is lactating
• Presence of a significant psychiatric condition that, in the opinion of the site Principal Investigator (PI) or appropriate sub-investigator, precludes study participation
• History of drug abuse or alcohol abuse within 6 months of enrollment that, in the opinion of the site PI or appropriate sub-investigator, precludes study participation
• Has a significant acute illness (with or without fever), as determined by the site PI or appropriate sub-investigator, within 72 hours prior to dosing\* \*If the participant meets all other eligibility criteria, they may be enrolled and dosed once they meet this eligibility criterion. If the illness resolves within the 28-day screening window, they do not need to be rescreened, otherwise they will need to be rescreened
• Currently enrolled in or plans to participate in another clinical trial with an investigational agent

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (3)

Duke Vaccine and Trials Unit

Durham, North Carolina, 27703, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232-0011, United States

Location

Baylor College of Medicine

Houston, Texas, 77030-3411, United States

Location

MeSH Terms

Conditions

Influenza in Birds; Influenza, Human

Interventions

Sodium Chloride

Condition Hierarchy (Ancestors)

Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Infections; Bird Diseases; Animal Diseases; Respiratory Tract Infections; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: Stage 2 is double-blinded, only individuals delegated to unblinded activities will know study vaccination assignments. As there is no placebo, we do not anticipate unintentional unblinding due to effects of the investigational agents. As the products are physically indistinguishable, no blinding sleeve or unblinded administrator will be required. Laboratory personnel performing assays will receive study samples blinded to participant data, as appropriate to avoid introducing bias in immunogenicity analysis.
• Purpose: PREVENTION
• Intervention Model: SEQUENTIAL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 29, 2025
• First Posted: June 13, 2025
• Study Start: June 12, 2025
• Primary Completion (Estimated): May 15, 2026
• Study Completion (Estimated): May 15, 2026
• Last Updated: January 30, 2026

Record last verified: 2025-09-10

Locations

US (3)