A Phase 2, Randomized, Stratified, Observer-Blind Clinical Study to Evaluate Safety and Immunogenicity of an MF59-Adjuvanted Quadrivalent Subunit Inactivated Influenza Vaccine in Older Adults
| Registry | NCT04576702 |
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| Status | Completed |
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| Phase | Phase 2 |
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| Study type | Interventional; randomized, parallel, masking: quadruple, prevention |
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| Enrollment | 471 (Actual) |
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| Sponsor | Seqirus (Industry) |
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| Conditions | Influenza, Human |
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| Interventions | Investigational aIIV4c, IIV4c, aIIV4, RIV4 (Biological) |
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| Dates | start 2020-10-08, primary completion 2021-03-19, completion 2021-05-24, first posted 2020-10-06, last updated 2024-04-17 |
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| Locations | 21 sites in United States |
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Related Papers Related Patents Related Grants Related Experts
All trials for Influenza All trials for Human All trials of Investigational aIIV4c All trials of IIV4c
-Summary
This Phase 2, randomized, observer-blind, active controlled clinical study is evaluating the safety and immunogenicity of the investigational MF59-Adjuvanted Quadrivalent Subunit Inactivated Influenza Vaccine. Approximately 480 subjects are to be randomized into 1 of 4 possible treatment groups (investigational Influenza Vaccine or licensed Quadrivalent Influenza Vaccine comparators) at 120 participants per group. Every participant will receive an influenza vaccine injection on Day 1 and will be followed up for approximately 6 months following injection. The primary immunogenicity analysis is based on Day 29 serum.
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+Arms and interventions
| Arm | Type | Interventions | Description |
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| Investigational aIIV4c group | Experimental | Biological: Investigational aIIV4c | aIIV4c will be administered as a single dose intramuscularly on Day 1 |
| licensed IIV4c group | Active comparator | Biological: IIV4c | IIV4c will be administered as a single dose intramuscularly on Day 1 |
| licensed aIIV4 group | Active comparator | Biological: aIIV4 | aIIV4 will be administered as a single dose intramuscularly on Day 1 |
| licensed RIV4 group | Active comparator | Biological: RIV4 | RIV4 will be administered as a single dose intramuscularly on Day 1 |
- Investigational aIIV4c (Biological): Investigational MF59 Adjuvanted Cell-derived Quadrivalent Influenza vaccine, containing four influenza virus strains (A/H1N1, A/H3N2, B/Yamagata and Victoria lineage) recommended by the WHO (World Health Organization) for quadrivalent vaccines for the respective season.
- IIV4c (Biological): Licensed, Non-adjuvanted, Cell-derived Quadrivalent Influenza Vaccine containing four influenza virus strains (A/H1N1, A/H3N2, B/Yamagata and Victoria lineage) recommended by the WHO for quadrivalent vaccines for the respective season.
- aIIV4 (Biological): Licensed, MF59-Adjuvanted, egg-derived Quadrivalent Influenza Vaccine containing four influenza virus strains (A/H1N1, A/H3N2, B/Yamagata and Victoria lineage) recommended by the WHO for quadrivalent vaccines for the respective season.
- RIV4 (Biological): Licensed, Recombinant Quadrivalent Influenza Vaccine containing four influenza virus strains (A/H1N1, A/H3N2, B/Yamagata and Victoria lineage) recommended by the WHO for quadrivalent vaccines for the respective season.
+Outcome measures
Primary outcomes
- Immunogenicity Endpoint: Geometric Mean Titer (GMT) Against the A/H1N1, B/Victoria and B/Yamagata Vaccine Strains by Hemagglutination Inhibition (HI) Assay and Against A/H3N2 Strain Using Microneutralization Assay Using Cell-derived Target Viruses [28 days post-vaccination]
- Immunogenicity Endpoint: Geometric Mean Ratio (GMR) (GMR is GMT Ratio of aIIV4c/Comparator) Against the A/H1N1, B/Victoria and B/Yamagata Vaccine Strains by HI Assay and Against A/H3N2 Strain Using MN Assay Using Cell-derived Target Viruses [28 days post-vaccination]
- Immunogenicity Endpoint: Percentage of Subjects Achieving Seroconversion for the A/H1N1, B/Victoria and B/Yamagata Strains by HI Assay and Against A/H3N2 Strain Using MN Assay Using Cell-derived Target Viruses [28 days post-vaccination]: Seroconversion is defined as ≥4-fold increase in titer postvaccination in those with pre-vaccination titer above or equal to the Lower Limit of Quantitation (LLOQ) (≥1:10), or a post-vaccination titer ≥1:40 for subjects with baseline titer below the LLOQ (1:10) for HI titers
- Immunogenicity Endpoint: Percentage of Subjects With HI Titer ≥1:40 for A/H1N1, B/Yamagata and B/Victoria Strains (HI Assay) Using Cell-derived Target Viruses [28 days post-vaccination]
Secondary outcomes
- Safety Endpoint: The Percentage of Subjects With Solicited Local and Systemic Reactions [7 days post-vaccination]: The percentage of subjects with at least one solicited AE Day 1 through Day 7 after study vaccination.
- Safety Endpoint: The Percentage of Subjects With Any Unsolicited Adverse Events [28 days post-vaccination]: The percentage of subjects with at least one unsolicited AE from Day 1 to Day 29.
Related AEs = considered at least possibly related to study vaccination by the investigator.
- Safety Endpoint: The Percentage of Subjects With Serious Adverse Events (SAEs), AEs Leading to Withdrawal, Adverse Events of Special Interest (AESI) and Medically Attended Adverse Events (MAAEs) During the Entire Study Period [180 days post-vaccination]
- Immunogenicity Endpoint: Geometric Mean Titer (GMT) Against the A/H1N1, B/Victoria and B/Yamagata Vaccine Strains by Microneutralization (MN) Assay Using Cell-derived Target Viruses [28 days post-vaccination]
- Immunogenicity Endpoint: GMR (GMR is GMT Ratio of aIIV4c/Comparator) Against the A/H1N1, B/Victoria and B/Yamagata Vaccine Strains by Microneutralization Assay Using Cell-derived Target Viruses [28 days post-vaccination]
- Immunogenicity Endpoint: Percentage of Subjects Achieving Seroconversion for the A/H1N1, B/Victoria and B/Yamagata Strains by MN Assay Using Cell-derived Target Viruses [28 days post-vaccination]: Seroconversion is defined as ≥4-fold increase in titer postvaccination in those with pre-vaccination titer above or equal to the Lower Limit of Quantitation (LLOQ) (≥1:10), or a post-vaccination titer ≥1:40 for subjects with baseline titer below the LLOQ (1:10) for HI titers
- Immunogenicity Endpoint: Geometric Mean Titer (GMT) Against the A/H1N1, B/Victoria and B/Yamagata Vaccine Strains by Hemagglutination Inhibition (HI) Assay Using Cell-derived Target Viruses [180 days post-vaccination]
- Immunogenicity Endpoint: GMR (GMR is GMT Ratio of aIIV4c/Comparator) Against the A/H1N1, B/Victoria and B/Yamagata Vaccine Strains by Hemagglutination Inhibition (HI) Assay Using Cell-derived Target Viruses [180 days post-vaccination]
- Immunogenicity Endpoint: Percentage of Subjects With HI Titer ≥1:40 for A/H1N1, B/Yamagata and B/Victoria Strains (HI Assay) Using Cell-derived Target Viruses [180 days post-vaccination]
- Immunogenicity Endpoint: Geometric Mean Titer (GMT) Against the A/H1N1, A/H3N2, B/Victoria and B/Yamagata Vaccine Strains by MN Assay Using Cell-derived Target Viruses [180 days post-vaccination]
- Immunogenicity Endpoint: GMR (GMR is GMT Ratio of aIIV4c/Comparator) Against the A/H1N1, A/H3N2, B/Victoria and B/Yamagata Vaccine Strains by MN Assay Using Cell-derived Target Viruses [180 days post-vaccination]
+Eligibility
Sex: All, ages: 50 Years to any, accepts healthy volunteers
Inclusion Criteria:
1. Individuals 50 years of age and older on the day of informed consent.
2. Individuals who have voluntarily given written consent after the nature of the study has been explained according to local regulatory requirements, prior to study entry.
3. Individuals who can comply with study procedures including follow-up.
4. Males, females of non-childbearing potential or females of childbearing potential who are using an effective birth control method, at least 30 days prior to informed consent, which they intend to use for at least 2 months after the study vaccination.
Exclusion Criteria:
1. Females of childbearing potential who are pregnant, lactating, or who have not adhered to a specified set of contraceptive methods from at least 30 days prior to informed consent and who do not plan to do so until 2 months after the study vaccination.
2. Progressive, unstable or uncontrolled clinical conditions.
3. Hypersensitivity, including allergy, to any component of vaccines, medicinal products or medical equipment whose use is foreseen in this study.
4. History of any medical condition considered an adverse event of special interest.
5. Known history of Guillain Barré syndrome or another demyelinating disease such as encephalomyelitis and transverse myelitis.
6. Clinical conditions representing a contraindication to intramuscular administration of vaccines or blood draw.
7. Abnormal function of the immune system resulting from:
1. Clinical conditions
2. Systemic administration of corticosteroids (PO/IV/IM) at a dose of ≥ 20 mg/day of prednisone or equivalent for more than 14 consecutive days within 90 days prior to informed consent5.
3. Administration of antineoplastic and immunomodulating agents or radiotherapy within 90 days prior to informed consent.
8. Received immunoglobulins or any blood products within 180 days prior to informed consent.
9. Received an investigational or non-registered medicinal product within 30 days prior to vaccination.
10. Individuals who received any other vaccines within 14 days (for inactivated vaccines) or 28 days (for live vaccines) prior to enrolment in this study or who are planning to receive any vaccine within 28 days from the study vaccines.
11. Study personnel or immediate family or household member of study personnel.
12. Receipt of any influenza vaccine within 6 months prior to vaccination in this study, or plan to receive an influenza vaccine during the study period.
13. Acute (severe) febrile illness
14. Any other clinical condition that, in the opinion of the investigator, might interfere with the results of the study or pose additional risk to the subject due to participation in the study.
+Posted results
Participant flow
| Milestone | Investigational aIIV4c Group | Licensed IIV4c Group | Licensed aIIV4 Group | Licensed RIV4 Group |
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| Started | 116 | 119 | 116 | 120 |
| Completed | 112 | 114 | 112 | 116 |
| Not completed | 4 | 5 | 4 | 4 |
Outcome results
- Immunogenicity Endpoint: Geometric Mean Titer (GMT) Against the A/H1N1, B/Victoria and B/Yamagata Vaccine Strains by Hemagglutination Inhibition (HI) Assay and Against A/H3N2 Strain Using Microneutralization Assay Using Cell-derived Target Viruses (Primary), Geometric mean, titer: Investigational aIIV4c Group 19.5 (15.5 to 24.5); Licensed IIV4c Group 17.04 (13.6 to 21.3); Licensed aIIV4 Group 21.85 (17.4 to 27.5); Licensed RIV4 Group 18.05 (14.5 to 22.5)
- Immunogenicity Endpoint: Geometric Mean Ratio (GMR) (GMR is GMT Ratio of aIIV4c/Comparator) Against the A/H1N1, B/Victoria and B/Yamagata Vaccine Strains by HI Assay and Against A/H3N2 Strain Using MN Assay Using Cell-derived Target Viruses (Primary), Geometric mean, Ratio: Licensed IIV4c Group 1.31 (0.96 to 1.79); Licensed aIIV4 Group 1.22 (0.89 to 1.68); Licensed RIV4 Group 0.84 (0.62 to 1.15)
- Immunogenicity Endpoint: Percentage of Subjects Achieving Seroconversion for the A/H1N1, B/Victoria and B/Yamagata Strains by HI Assay and Against A/H3N2 Strain Using MN Assay Using Cell-derived Target Viruses (Primary), Number, percentage of subjects: Investigational aIIV4c Group 61.8 (52.1 to 70.9); Licensed IIV4c Group 54.4 (44.8 to 63.7); Licensed aIIV4 Group 50.5 (40.7 to 60.2); Licensed RIV4 Group 61.2 (51.7 to 70.1)
- Immunogenicity Endpoint: Percentage of Subjects With HI Titer ≥1:40 for A/H1N1, B/Yamagata and B/Victoria Strains (HI Assay) Using Cell-derived Target Viruses (Primary), Number, percentage of subjects: Investigational aIIV4c Group 44.5 (35.1 to 54.3); Licensed IIV4c Group 36.8 (28.0 to 46.4); Licensed aIIV4 Group 41.3 (31.9 to 51.1); Licensed RIV4 Group 38.8 (29.9 to 48.3)
- Safety Endpoint: The Percentage of Subjects With Solicited Local and Systemic Reactions (Secondary), Count of participants, Participants: Investigational aIIV4c Group 85; Licensed IIV4c Group 72; Licensed aIIV4 Group 83; Licensed RIV4 Group 80
- Safety Endpoint: The Percentage of Subjects With Any Unsolicited Adverse Events (Secondary), Count of participants, Participants: Investigational aIIV4c Group 23; Licensed IIV4c Group 27; Licensed aIIV4 Group 23; Licensed RIV4 Group 29
- Safety Endpoint: The Percentage of Subjects With Serious Adverse Events (SAEs), AEs Leading to Withdrawal, Adverse Events of Special Interest (AESI) and Medically Attended Adverse Events (MAAEs) During the Entire Study Period (Secondary), Count of participants, Participants: Investigational aIIV4c Group 2; Licensed IIV4c Group 1; Licensed aIIV4 Group 4; Licensed RIV4 Group 6
- Immunogenicity Endpoint: Geometric Mean Titer (GMT) Against the A/H1N1, B/Victoria and B/Yamagata Vaccine Strains by Microneutralization (MN) Assay Using Cell-derived Target Viruses (Secondary), Geometric mean, titer: Investigational aIIV4c Group 158.64 (122.0 to 206.3); Licensed IIV4c Group 102.88 (79.5 to 133.1); Licensed aIIV4 Group 162.19 (124.6 to 211.1); Licensed RIV4 Group 138.73 (107.5 to 179.0)
- Immunogenicity Endpoint: GMR (GMR is GMT Ratio of aIIV4c/Comparator) Against the A/H1N1, B/Victoria and B/Yamagata Vaccine Strains by Microneutralization Assay Using Cell-derived Target Viruses (Secondary), Geometric mean, ratio: Licensed IIV4c Group 1.22 (0.88 to 1.68); Licensed aIIV4 Group 1.20 (0.87 to 1.66); Licensed RIV4 Group 0.73 (0.53 to 1.01)
- Immunogenicity Endpoint: Percentage of Subjects Achieving Seroconversion for the A/H1N1, B/Victoria and B/Yamagata Strains by MN Assay Using Cell-derived Target Viruses (Secondary), Number, percentage of subjects: Investigational aIIV4c Group 61.8 (52.1 to 70.9); Licensed IIV4c Group 60.5 (50.9 to 69.6); Licensed aIIV4 Group 53.2 (43.4 to 62.8); Licensed RIV4 Group 70.7 (61.5 to 78.8)
- Immunogenicity Endpoint: Geometric Mean Titer (GMT) Against the A/H1N1, B/Victoria and B/Yamagata Vaccine Strains by Hemagglutination Inhibition (HI) Assay Using Cell-derived Target Viruses (Secondary), Geometric mean, titer: Investigational aIIV4c Group 156.47 (127.6 to 191.9); Licensed IIV4c Group 144.08 (117.6 to 176.5); Licensed aIIV4 Group 157.72 (128.9 to 193.0); Licensed RIV4 Group 198.17 (162.3 to 242.0)
- Immunogenicity Endpoint: GMR (GMR is GMT Ratio of aIIV4c/Comparator) Against the A/H1N1, B/Victoria and B/Yamagata Vaccine Strains by Hemagglutination Inhibition (HI) Assay Using Cell-derived Target Viruses (Secondary), Geometric mean, Ratio: Licensed IIV4c Group 1.09 (0.82 to 1.44); Licensed aIIV4 Group 0.99 (0.75 to 1.31); Licensed RIV4 Group 0.79 (0.60 to 1.04)
- Immunogenicity Endpoint: Percentage of Subjects With HI Titer ≥1:40 for A/H1N1, B/Yamagata and B/Victoria Strains (HI Assay) Using Cell-derived Target Viruses (Secondary), Number, percentage of subjects: Investigational aIIV4c Group 88.9 (81.4 to 94.1); Licensed IIV4c Group 87.3 (79.6 to 92.9); Licensed aIIV4 Group 87.3 (79.6 to 92.9); Licensed RIV4 Group 87.6 (80.1 to 93.1)
- Immunogenicity Endpoint: Geometric Mean Titer (GMT) Against the A/H1N1, A/H3N2, B/Victoria and B/Yamagata Vaccine Strains by MN Assay Using Cell-derived Target Viruses (Secondary), Geometric mean, titer: Investigational aIIV4c Group 481.49 (378.4 to 612.6); Licensed IIV4c Group 523.03 (410.7 to 666.0); Licensed aIIV4 Group 502.85 (396.2 to 638.2); Licensed RIV4 Group 841.31 (664.8 to 1064.7)
- Immunogenicity Endpoint: GMR (GMR is GMT Ratio of aIIV4c/Comparator) Against the A/H1N1, A/H3N2, B/Victoria and B/Yamagata Vaccine Strains by MN Assay Using Cell-derived Target Viruses (Secondary), Geometric mean, ratio: Licensed IIV4c Group 0.92 (0.66 to 1.28); Licensed aIIV4 Group 0.96 (0.69 to 1.33); Licensed RIV4 Group 0.57 (0.41 to 0.79)
Adverse events
Time frame: Time frame for all-cause mortality: 6 months SAEs: Day 1 to Day 181; Nonserious unsolicited AEs: Day 1 to Day 29; Solicited AEs: Day 1 to Day 7 after vaccination
| Arm | Deaths | Serious adverse events | Other adverse events |
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| Investigational aIIV4c Group | 1/116 (0.9%) | 2/116 (1.7%) | 86/116 (74.1%) |
| Licensed IIV4c Group | 0/119 (0.0%) | 1/119 (0.8%) | 77/119 (64.7%) |
| Licensed aIIV4 Group | 0/116 (0.0%) | 4/116 (3.4%) | 84/116 (72.4%) |
| Licensed RIV4 Group | 0/120 (0.0%) | 6/120 (5.0%) | 83/120 (69.2%) |
Serious adverse events by term
| Term | Organ system | Investigational aIIV4c Group | Licensed IIV4c Group | Licensed aIIV4 Group | Licensed RIV4 Group |
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| Atrioventricular block second degree | Cardiac disorders | 0/116 | 0/119 | 0/116 | 1/120 |
| Cardiac failure congestive | Cardiac disorders | 1/116 | 0/119 | 0/116 | 0/120 |
| Coronary artery stenosis | Cardiac disorders | 0/116 | 0/119 | 1/116 | 0/120 |
| Ventricular tachycardia | Cardiac disorders | 0/116 | 1/119 | 0/116 | 0/120 |
| Enterocutaneous fistula | Gastrointestinal disorders | 0/116 | 0/119 | 1/116 | 0/120 |
| Contrast media allergy | Immune system disorders | 0/116 | 0/119 | 0/116 | 1/120 |
| COVID-19 | Infections and infestations | 1/116 | 0/119 | 1/116 | 2/120 |
| Scrotal abscess | Infections and infestations | 0/116 | 0/119 | 0/116 | 1/120 |
| Sepsis | Infections and infestations | 0/116 | 0/119 | 0/116 | 1/120 |
| Anaemia postoperative | Injury, poisoning and procedural complications | 0/116 | 0/119 | 1/116 | 0/120 |
| Clear cell renal cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 0/116 | 0/119 | 0/116 | 1/120 |
| Cerebrovascular accident | Nervous system disorders | 0/116 | 0/119 | 1/116 | 0/120 |
| Guillain-Barre syndrome | Nervous system disorders | 1/116 | 0/119 | 0/116 | 0/120 |
| Acute kidney injury | Renal and urinary disorders | 0/116 | 0/119 | 0/116 | 1/120 |
| Nephrolithiasis | Renal and urinary disorders | 0/116 | 0/119 | 0/116 | 1/120 |
| Chronic obstructive pulmonary disease | Respiratory, thoracic and mediastinal disorders | 1/116 | 0/119 | 0/116 | 0/120 |
| Deep vein thrombosis | Vascular disorders | 0/116 | 0/119 | 1/116 | 0/120 |
Other adverse events by term
| Term | Organ system | Investigational aIIV4c Group | Licensed IIV4c Group | Licensed aIIV4 Group | Licensed RIV4 Group |
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| Nausea | Gastrointestinal disorders | 16/116 | 12/119 | 13/116 | 15/120 |
| chills | General disorders | 15/116 | 8/119 | 12/116 | 12/120 |
| fatigue | General disorders | 50/116 | 29/119 | 30/116 | 40/120 |
| Induration | General disorders | 6/116 | 5/119 | 6/116 | 4/120 |
| Injection site pain | General disorders | 70/116 | 51/119 | 66/116 | 51/120 |
| loss of appetite | Metabolism and nutrition disorders | 17/116 | 13/119 | 15/116 | 20/120 |
| arthralgia | Musculoskeletal and connective tissue disorders | 35/116 | 19/119 | 23/116 | 28/120 |
| myalgia | Musculoskeletal and connective tissue disorders | 40/116 | 23/119 | 26/116 | 27/120 |
| headache | Nervous system disorders | 37/116 | 28/119 | 29/116 | 36/120 |
| erythema | Skin and subcutaneous tissue disorders | 6/116 | 4/119 | 3/116 | 2/120 |
+Locations (21)
| Facility | City | Country | Status |
|---|
| 4022 - Coastal Clinical Research, an AMR company | Mobile, Alabama | United States | |
| 4002 - Clinical Research Consortium, an AMR company | Tempe, Arizona | United States | |
| 4006 - Westside Center for Clinical Research | Jacksonville, Florida | United States | |
| 4013 - Jacksonville Center for Clinical Research | Jacksonville, Florida | United States | |
| 4021 - Research Centers of America, LLC | Oakland, Florida | United States | |
| 4023 - Advanced Clinical Research | Boise, Idaho | United States | |
| 4010 - Heartland Research Associates, LLC | Newton, Kansas | United States | |
| 4016 - Heartland Research Associates, LLC - An AMR Company | Wichita, Kansas | United States | |
| 4001 - Central Kentucky Research Associates, an AMR company | Lexington, Kentucky | United States | |
| 4014 - Medpharmi | Kenner, Louisiana | United States | |
| 4008 - The Center for Pharmaceutical Research, an AMR company | Kansas City, Missouri | United States | |
| 4024 - Sundance Clinical Research, LLC | St Louis, Missouri | United States | |
| 4009 - Meridian Clinical Research, LLC | Omaha, Nebraska | United States | |
| 4007 - Regional Clinical Research / United Medical Associates | Binghamton, New York | United States | |
| 4012 - M3 Wake Research, Inc. | Raleigh, North Carolina | United States | |
| 4004 - Sterling research | Cincinnati, Ohio | United States | |
| 4017 - Rapid Medical Research, Inc. | Cleveland, Ohio | United States | |
| 4011 - Lynn Health Science Institute | Oklahoma City, Oklahoma | United States | |
| 4005 - Clinical Trials of Texas, Inc. | San Antonio, Texas | United States | |
| 4018 - Martin Diagnostic Clinic | Tomball, Texas | United States | |
| 4020 - Advanced Clinical Research | West Jordan, Utah | United States | |
+Publications
- Results publication: Essink BJ, Vermeulen W, Andrade C, de Rooij R, Isakov L, Casula D, Albano FR. A randomised phase 2 immunogenicity and safety study of a MF59-adjuvanted quadrivalent subunit inactivated cell-derived influenza vaccine (aQIVc) in adults aged 50 years and older. Vaccine. 2025 Apr 2;51:126791. doi: 10.1016/j.vaccine.2025.126791. Epub 2025 Feb 12. PMID 39946829
+Study documents
+Investigators
- Clinical Program Director, Study director, Seqirus