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

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE1

Total Enrollment

80 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-06-12

Study Completion Date

2026-05-15

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Avian Influenza

Keywords

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

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

PREVENTION

Blinding Strategy

DOUBLE

Participants Outcome Assessors

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.

Intervention Type OTHER

0.9% Sodium Chloride Injection

Interventions

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H5 AC-Anhui RNA Vaccine

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.

Intervention Type BIOLOGICAL

H5 Astrakhan RNA Vaccine

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.

Intervention Type BIOLOGICAL

Sodium Chloride, 0.9%

0.9% Sodium Chloride Injection

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

1. Provides written informed consent prior to the initiation of any trial procedures
2. Can understand and agrees to comply with all planned trial procedures and be available for all study visits
3. Adult volunteers, age 18-49 years, inclusive, at time of enrollment.

Exclusion Criteria

1. was first diagnosed within 3 months of enrollment with a clinically significant condition, in the opinion of investigator
2. had non-elective surgery, clinically significant medical procedure, or hospitalization within 3 months of enrollment;
3. 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
4. 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.
5. 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.
6. Must agree to refrain from donating blood or blood products during the first 6 months of the study
7. 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

1. Positive pregnancy test at screening or prior to vaccine dose
2. Participant who is lactating
3. Presence of a significant psychiatric condition that, in the opinion of the site Principal Investigator (PI) or appropriate sub-investigator, precludes study participation
4. 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
5. 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
6. Currently enrolled in or plans to participate in another clinical trial with an investigational agent
7. 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.
8. Received any live-attenuated or mRNA vaccine in the 28 days prior or any other vaccine in the 14 days prior to study vaccination
9. 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
10. 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)
11. Abnormal heart rate (Grade 2 or higher) at time of vaccination
12. Known and current human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV) infection, based on medical history
13. Extended exposure (e.g., occupational or home exposure) to cattle or poultry since March 1, 2024
14. Ingestion of non-pasteurized milk since March 1, 2024, or plans to drink non-pasteurized milk during participation in the trial
15. Prior receipt of an influenza A/H5 vaccine
16. History of myocarditis or pericarditis
17. Has any medical disease or condition\*\*\*\*\* that, in the opinion of the site PI or appropriate sub-investigator, precludes study participation\*\*\*\*\*\* \*\*\*\*\*Medical conditions include, but are not limited to, kidney disease with creatinine clearance \< 89 mL/min/1.73 cm2 Chronic Kidney Disease Epidemiology Collaboration method (CKD-EPI); known active liver disease; ischemic heart disease, clinically significant cardiac conduction disorder, arrythmia requiring treatment, congenital long QT syndrome, uncompensated heart failure; diabetes requiring insulin; neuropathy or myopathy; history of Guillain-Barré Syndrome; and malignancy (not including squamous cell skin cancer, basal cell skin cancer, or cervical lowgrade squamous intraepithelial lesions) \*\*\*\*\*\*Participation may be precluded due to safety concern or inability to adequately evaluate clinical trial endpoints.

Minimum Eligible Age

18 Years

Maximum Eligible Age

49 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Responsible Party

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Responsibility Role SPONSOR

Locations

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Duke Vaccine and Trials Unit

Durham, North Carolina, United States

Site Status

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Site Status

Baylor College of Medicine

Houston, Texas, United States

Site Status

Countries

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United States

Provided Documents

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Document Type: Informed Consent Form

View Document

Other Identifiers

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24-0024

Identifier Type: -

Identifier Source: org_study_id

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

Study Results

Basic Information

Brief Summary

Detailed Description

Conditions

Keywords

Study Design

Study Groups

Stage 1 Group 1

H5 AC-Anhui RNA Vaccine

Sodium Chloride, 0.9%

Stage 1 Group 2

H5 AC-Anhui RNA Vaccine

Sodium Chloride, 0.9%

Stage 1 Group 3

H5 AC-Anhui RNA Vaccine

Sodium Chloride, 0.9%

Stage 2 Group 4

H5 AC-Anhui RNA Vaccine

Sodium Chloride, 0.9%

Stage 2 Group 5

H5 Astrakhan RNA Vaccine

Sodium Chloride, 0.9%

Interventions

H5 AC-Anhui RNA Vaccine

H5 Astrakhan RNA Vaccine

Sodium Chloride, 0.9%

Eligibility Criteria

Inclusion Criteria

Exclusion Criteria

Sponsors

National Institute of Allergy and Infectious Diseases (NIAID)

Responsible Party

Locations

Duke Vaccine and Trials Unit

Vanderbilt University Medical Center

Baylor College of Medicine

Countries

Provided Documents

Document Type: Informed Consent Form

Other Identifiers

24-0024