H5 RNA Vaccines for Avian Flu

Not currently recruiting at 2 trial locations

Overseen By C. Buddy Creech

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Must not be taking: Immunosuppressants, Immune modulators

Disqualifiers: Pregnancy, Lactation, Drug abuse, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 3

Duration: 4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests new RNA vaccines to determine their safety in protecting against bird flu. The study will evaluate different doses of two vaccines: the H5 AC-Anhui RNA Vaccine and the H5 Astrakhan RNA Vaccine, to identify the safest and most effective option. It seeks healthy adults who have been generally well, without recent major surgeries or new medications, and who have not received bird flu shots before. Participants must be willing to follow all study procedures and visits. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new vaccine.

Do I need to stop taking my current medications to join the trial?

The trial does not specify if you need to stop all current medications, but you cannot use certain medications like systemic immunosuppressive drugs, immune modulators, oral corticosteroids, and systemic antineoplastic agents within 30 days before starting the trial and through Day 57. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

In earlier studies, the H5 AC-Anhui RNA vaccine showed promising safety results. Research indicates that it reduces infection severity, with fewer symptoms such as weight loss and fever, suggesting it is generally well-tolerated. Similarly, the H5 Astrakhan RNA vaccine demonstrated good safety and effectively created an immune response in animals, like ferrets, which is a positive sign for its use in humans.

Since both vaccines are in the early stages of testing, phase 1 trials primarily focus on assessing safety in healthy volunteers. Researchers closely monitor any side effects to ensure participant safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these H5 RNA vaccines for avian flu because they use cutting-edge RNA technology, which is different from traditional flu vaccines that typically use inactivated or live-attenuated viruses. This RNA approach allows for a rapid response to emerging flu strains, potentially leading to faster vaccine development and deployment. Additionally, the vaccines target the H5 subtype of avian flu, which poses a significant threat due to its potential to cause pandemics. By focusing on this specific subtype, these vaccines could offer targeted protection against a serious health threat.

What evidence suggests that this trial's vaccines could be effective for avian flu?

Research has shown that the H5 AC-Anhui RNA vaccine, which participants in this trial may receive, may help reduce the severity of avian flu infections. Studies found it worked better than other vaccines by minimizing weight loss and fever in animals, indicating it could lessen symptoms. For the H5 Astrakhan RNA vaccine, another treatment option in this trial, animal studies showed it produced high levels of antibodies, which are important for fighting the virus. These antibodies neutralized the virus in lab tests, suggesting strong potential for protection against avian flu. Both vaccines have shown promising early results, but human trials are needed to confirm their effectiveness. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

Healthy adults aged 18-49 can join this trial to test two new H5 influenza vaccines. Participants will be closely monitored for about 6 months after receiving the vaccine doses. The study excludes details on specific inclusion and exclusion criteria.

Inclusion Criteria

Provides written informed consent prior to the initiation of any trial procedures

I am between 18 and 49 years old.

My BMI is between 18 and 35, and I weigh 130 kg or less.

Exclusion Criteria

I haven't had any live or mRNA vaccines in the last 28 days or any vaccines in the last 14 days.

Prior receipt of an influenza A/H5 vaccine

Has a history of anaphylaxis to any drug compound, vaccine, food, or other substance

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 day

1 visit (in-person)

Treatment

Participants receive two doses of H5 AC-Anhui RNA vaccine or H5 Astrakhan RNA vaccine on days 1 and 29

4 weeks

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after the second dose of vaccine

6 months

Multiple visits (in-person and virtual)

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• H5 AC-Anhui RNA Vaccine
• H5 Astrakhan RNA Vaccine

Trial Overview The trial is testing the safety of two mRNA-based flu vaccines: H5 AC-Anhui RNA and H5 Astrakhan RNA, given in different dosages (12.5 mcg, 25 mcg, or 50 mcg). It's a double-blind study where neither participants nor researchers know who gets which vaccine.

How Is the Trial Designed?

Group I: Stage 2 Group 5 Experimental Treatment 2 Interventions

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

Group II: Stage 2 Group 4 Experimental Treatment 2 Interventions

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

Group III: Stage 1 Group 3 Experimental Treatment 2 Interventions

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

Group IV: Stage 1 Group 2 Experimental Treatment 2 Interventions

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

Group V: Stage 1 Group 1 Experimental Treatment 2 Interventions

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

Who Is Running the Clinical Trial?

National Institute of Allergy and Infectious Diseases (NIAID)

Lead Sponsor

Trials

3,361

Recruited

5,516,000+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT07019883

NCT07019883 | A Study to Evaluate the Safety and ... 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.

2. nature.com nature.com/articles/s41586-025-09626-3

A vaccine central in A(H5) influenza antigenic space ... Moreover, AC-AnhuiVACC outperformed AnhuiVACC in reducing infection severity, evidenced by reduced body weight loss, body temperature increase, ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11566024/

A vaccine antigen central in influenza A(H5) virus antigenic ... In addition, AC-AnhuiVACC outperformed AnhuiVACC in reducing infection severity, evidenced by reduced body weight loss, body temperature increase, virus titers, ...

4. cidrap.umn.edu cidrap.umn.edu/avian-influenza-bird-flu/intranasal-vaccine-against-h5-avian-flu-provokes-broad-immune-response

Intranasal vaccine against H5 avian flu provokes broad ... Only recipients of the boosted intranasal vaccine showed strong immune priming. Even without a booster, the intranasal vaccine triggered mucosal ...

5. withpower.com withpower.com/trial/phase-1-influenza-in-birds-5-2025-3d6a4

H5 RNA Vaccines for Avian Flu 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.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT07019883?cond=influenza&intr=%20mRNA&page=3&rank=22

A Study to Evaluate the Safety and Immunogenicity of Two ... 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 ...