The purpose of this study is to evaluate the safety, tolerance, and immunogenicity of MAS-1-Adjuvanted seasonal inactivated influenza vaccine (IIV) (MER4101) with hemagglutinin dose escalation compared to non-adjuvanted comparator IIV standard dose (SD) in healthy adults and high dose (HD) IIV in ambulatory elderly subjects. Hypothesis: Reduced HA dose IIV formulated in MAS-1 adjuvant (MER4101) has been shown under Phase 1A to be safe, tolerable and demonstrated a more robust and durable immune response to IIV over 6 months post-vaccination in healthy young adults 18 - 49 years of age compared to SD IIV. Under phase 1B, the 9 µg/HA dose of IIV in 0.3 mL MAS-1 was safe and well tolerated and immunogenically comparable to or better than 60 µg/HA HD IIV control over 3 to 6 months post-vaccination than HD IIV control. It is anticipated that the increased total dose of 15 µg HA antigen administered concurrently to opposite arms in 2 doses of 7.5 µg/HA IIV in 0.25 mL MAS-1 adjuvant emulsion will be safe, well tolerated, and more immunogenic than 9 µg/HA IIV in MAS-1, and will be more immunogenic when compared to HD IIV control in adults who are 65 years of age and older with the potential to provide better protection throughout the influenza season.
The study is a Phase 1A, 1B and 1B extension, randomized, double-blind, single-center, clinical trial, in healthy adults (18-49 years old) and ambulatory elderly subjects (aged 65 years and older). Phase IA evaluated the safety, tolerability and hemagglutination inhibition assay (HAI) antibody response to MER4101 at each of four escalating doses of seasonal inactivated influenza vaccine (IIV) hemagglutinin (HA) antigen with a fixed dose of a water-in-oil emulsion adjuvant MAS-1 (Mercia Adjuvant System-1), compared with licensed, unadjuvanted, standard dose (SD) of licensed inactivated trivalent influenza virus vaccine (IIV). Phase IB evaluated the optimal dose of IIV in MAS-1 selected under phase IA for safety, tolerability and HAI antibody response (from Phase 1A known to be 9 µg of HA antigen in 0.3 mL dose of MAS-1 adjuvanted emulsion) in ambulatory elderly subjects compared to high dose (HD) IIV. The Phase 1B extension will evaluate if the increased dose volume of MAS-1 (0.5 mL vs 0.3 mL) at the same 9 µg/HA adjuvanted IIV vaccine is safe, well tolerated and immunogenic, and then whether the increased dose of 15 µg/HA in 0.5 mL MAS-1 is safe, well tolerated and still more immunogenic in elderly subjects. The ability of standard dose (SD) IIV to protect against seasonal influenza virus infection in the elderly is less than vaccine efficacy observed in healthy young adults. The MAS-1-adjuvanted influenza virus vaccine offers the potential for higher seroconversion and seroprotection rates, hemagglutination inhibition (HAI) antibody titers relative to pre-vaccination HAI titers (GMFI), hemagglutinin (HA) antigen dose-sparing and cross-protection against antigenically divergent viral strains, and importantly, prolonged duration of protective immunity lasting up to at least 6 months post-vaccination in both the general adult population and the elderly, thereby providing potentially protective immunity throughout the influenza season. This study will determine if the adjuvanted vaccine formulated with one or more of the reduced HA antigen doses is safe. The study will also determine if it is likely to induce an improved HA antibody response (HAI) when compared to SD IIV in healthy adults and HD IIV in elderly subjects. This trial will inform future clinical trials in at-risk populations of older patients.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
QUADRUPLE
Enrollment
102
Fluzone quadrivalent Influenza Vaccine
Saint Louis University School of Medicine
St Louis, Missouri, United States
Number of Participants with solicited local and systemic AEs
Time frame: 14 Days after Vaccination
Number of Participants with Late-Onset Local and Systemic AEs
Time frame: 16 days after Vaccination for the remaining duration of the study
Number of Participants with laboratory abnormalities
Time frame: 7, 14 and 28 Days after Vaccination
Occurrence of vaccine-related SAEs
Time frame: Duration of Study
Geometric mean titer (GMT) of hemagglutination inhibition assay (HAI) antibodies
Time frame: 28 days after Vaccination
Seroconversion rate of HAI antibody titer
Time frame: 28 days after Vaccination
Geometric mean fold increase (GMFI) of HAI antibodies (post-vaccination titer relative to pre-vaccination titer)
Time frame: 28, 84, and 168 days after Vaccination
Occurrence of unsolicited AEs related to vaccine
Time frame: 1 to 14, 15 to 29, and 30 to 85 Days after Vaccination
Occurrence of adverse events of special interest (AESI)
Time frame: Up to 12 months after Vaccination
Comparison of rates of unsolicited AEs related to vaccine at intervals following vaccination
Time frame: 1 to 14 days, 15 to 29 days, and 30 to 85 days after Vaccination
Seroprotection rate of HAI antibody titers (proportion of participants with ≥40 reciprocal antibody titer)
Time frame: 7, 14, 28, 84, and 168 days after Vaccination
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