Avian Influenza
Conditions
Keywords
H5N1, Healthy Adults, Influenza, Novel H5 Central Antigen mRNA-LNP, Phase 1, Safety and Immunogenicity, Vaccine
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.
Detailed description
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.
Interventions
BIOLOGICALH5 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.
BIOLOGICALH5 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.
0.9% Sodium Chloride Injection
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Outcomes Assessor)
Masking description
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to 49 Years
Healthy volunteers
Yes
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. 4. 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: 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 | — |
| Geometric mean titers of homologous and heterologous H5-specific neutralizing antibodies (Neut) | 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 | Day 8 through Day 57 | 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 |
| Number and Percentage of participants demonstrating Hemagglutination Inhibition Antibody (HAI) titer seroprotection against homologous and heterologous H5-specific hemagglutinin | Day 1 through Day 57 | Seroprotection defined as \>/=1:40 titer |
| The number and percentage of participants achieving Neut seroconversion since pre-vaccination (Day 1) against the homologous and heterologous H5-specific hemagglutinin | Day 8 through Day 57 | 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 |
Countries
United States
Outcome results
None listed