Safety, Reactogenicity, and Immunogenicity Study of a Self-Amplifying MRNA Influenza Vaccine in Healthy Adults

Phase 1

Completed

• Conditions: Influenza, Human
• Interventions: Biological: Placebo; Biological: sa-mRNA vaccine Dose 2; Biological: sa-mRNA vaccine Dose 3; Biological: sa-mRNA vaccine Dose 1

• Registration Number: NCT06028347
• Lead Sponsor: Seqirus

Brief Summary

This is a Phase 1, first-in-human, randomized, placebo-controlled, observer blind study. The effect of two doses of an investigational vaccine on safety, reactogenicity, kinetics and magnitude of the post-vaccination antibody response will be evaluated at different timepoints as compared to placebo in healthy adults.

Approximately 96 evaluable subjects will be enrolled in this study; n=72 receiving investigational vaccine and n=24 receiving placebo.

The study has a screening period (Day -28 to Day -1), a treatment period (Day 1 to Day 43) and a follow-up period (Day 44 to Day 202).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-08-31
• Study First Submitted QC: 2023-08-31
• Study First Posted: 2023-09-08
• Study Start: 2023-10-05
• Primary Completion: 2024-10-13
• Study Completion: 2024-10-13
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-26
• Last Update Posted: 2024-11-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 96

Inclusion Criteria

1. Individuals 18 to 49 years of age OR 65 to 85 years of age, inclusive on the day of informed consent.
2. Individuals with body mass index (BMI) between 18 and 32 kg/m2, inclusive, at screening .
3. Individuals who can comply with study procedures including follow-up .

Exclusion Criteria

1. Female participants of childbearing potential who are pregnant, lactating, or who have not adhered to a specified set of highly effective contraceptive methods from at least 30 days prior to informed consent and who do not plan to do so for the duration of the study.
2. Male participants who have not adhered to using barrier contraception such as a condom during at least 60 days after each vaccination, to prevent semen transfer to their sexual partners and prevent pregnancy of a female partner.
3. Progressive, unstable, or uncontrolled clinical conditions
4. Known hypersensitivity or allergy to any study vaccine component
5. Known history of Guillain-Barré syndrome or other demyelinating disease
6. Condition representing a contraindication to vaccination or blood draw
7. Abnormal function of immune system due to clinical condition, medications, or radiotherapy.
8. Receipt or planning to receive blood products, non-study vaccine, influenza vaccine, mRNA-platform vaccine within different timeframes; previous or from study vaccination.
9. Baseline abnormal clinically significant ECG, laboratory safety parameters or vital signs.
10. Plan to donate blood products (other than for this study), sperm, ova, tissues, or organs up to 60 days following the last vaccination.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	-
sa-mRNA vaccine dose 2	sa-mRNA vaccine Dose 2	-
sa-mRNA vaccine dose 3	sa-mRNA vaccine Dose 3	-
sa-mRNA vaccine dose 1	sa-mRNA vaccine Dose 1	-

Primary Outcome Measures

Name	Time	Method
Number and percentage of subjects with HAI titer ≥1:40, ≥1:80, ≥1:160 and ≥1:320	Day 1, Day 22, Day 43
Number and percentage of subjects with clinically significant abnormal vital signs and/or acute reactions	up to 60 minutes or within 6 hours post vaccination
Number and percentage of subjects reporting reactogenicity: Solicited local and systemic AEs	Day 1 to Day 14 of each post vaccination period
Number and percentage of subjects with Grade 3 or greater abnormal clinically significant hematology and chemistry laboratory values	Day 3 to Day 43
Seroconversion rate (SCR) by HAI assay	Day 1, Day 22, Day 43	SCR defined as the percentage of subjects with either a prevaccination HAI titer \<1:10 and a post-vaccination HAI titer ≥1:40, or a prevaccination HAI titer ≥1:10 and a ≥4-fold increase in post-vaccination
Number and percentage of subjects with grading shifts in hematology and chemistry laboratory assessments	Day 3 to Day 43
Serum antibody titer against the HA glycoprotein in terms of GMT, GMFI, and GMT ratio measured via HI assay	Day 1, Day 22, Day 43
Number and percentage of subjects reporting unsolicited AEs	Day 1 to Day 43
Number and percentage of subjects reporting AEs leading to study withdrawal, Adverse Events of Special Interest (AESIs), medically attended AEs (MAAEs), and serious adverse events (SAEs).	Day 1 to Day 202
Number and percentage of subjects with HAI titer ≥1:10 and <1:10 (lower limit of quantification [LLOQ])	Day 1, Day 22, Day 43

Secondary Outcome Measures

Name	Time	Method
Serum antibody titer against the NA glycoprotein in terms of GMT, GMFI, and GMT ratio measured via ELLA assay	Day 1, Day 22, Day 43, Day 202
Number and percentage of subjects with HAI titer ≥1:10 and <1:10 (LLOQ)	Day 202
Number and percentage of subjects with HAI titer ≥1:40, ≥1:80, ≥1:160 and ≥1:320	Day 202
Number and percentage of subjects with ≥4-fold increase in post-vaccination ELLA titer	Day 1, Day 22, Day 43, Day 202
Number and percentage of subjects with ≥4-fold increase in post-vaccination HAI titer	Day 1, Day 202
Seroconversion rate (SCR) by HAI assay	Day 1, Day 202
Serum antibody titer against the HA glycoprotein in terms of GMT, GMFI, and GMT ratio measured via HI assay	Day 1, Day 202

Trial Locations

Locations (2)

Nucleus network Melbourne Clinic; 🇦🇺 Melbourne, Victoria, Australia

Nucleus Network Brisbane Clinic; 🇦🇺 Brisbane, Queensland, Australia