First-in-Human Clinical Trial of a Mosaic Quadrivalent Influenza Vaccine Compared With a Licensed Inactivated Seasonal QIV in Healthy Adults
- Conditions
- InfluenzaSeasonal Influenza
- Interventions
- Registration Number
- NCT04896086
- Brief Summary
Background:
Influenza (flu) is a contagious respiratory illness. It is caused by influenza viruses that infect the nose, throat, and sometimes the lungs. Vaccines are given to teach the body to prevent or fight infection. Researchers want to study a new vaccine to prevent the seasonal flu.
Objective:
To see if the FluMos-v1 vaccine is safe and how the body responds to it.
Eligibility:
Healthy adults ages 18-50 years inclusive were enrolled.
Design:
Participants were screened through a separate protocol.
Participants were tested for COVID-19. They may have had a pregnancy test.
Participants received the investigational FluMos-v1 vaccine or the licensed inactivated seasonal quadrivalent influenza vaccine Flucelvax injected in the upper arm.
Participants completed a diary card for 7 days. They recorded any symptoms they had. They were given a thermometer to check their temperature. They were also given a ruler to measure any skin changes at the injection site.
Participants had about 10 study visits. They were asked how they were feeling and if they had taken any medications. They had blood drawn.
Some participants had an optional apheresis. Blood was removed through a needle in a vein in one arm. A machine separated the white blood cells. The rest of the blood was returned through a needle in a vein in the other arm.
Participation lasted for 40 weeks.
- Detailed Description
Design:
This was a Phase I, open-label, dose escalation study to evaluate the dose, safety, tolerability, and immunogenicity of the mosaic quadrivalent influenza vaccine VRC-FLUMOS0111-00-VP (FluMos-v1). The hypotheses were that the FluMos-v1 vaccine is safe and tolerable and would elicit an immune response. The primary objective was to evaluate the safety and tolerability of the investigational vaccine alone or with adjuvant in healthy adults. Secondary objectives were related to immunogenicity of the investigational vaccine and dosing regimen compared with the licensed inactivated seasonal Flucelvax (Registered Trademark) quadrivalent influenza vaccine (QIV) in healthy adults.
Study Products:
The investigational nanoparticle vaccine VRC-FLUMOS0111-00-VP (FluMos-v1) was developed by the Vaccine Research Center (VRC), National Institute of Allergy and Infectious Diseases (NIAID). FluMos-v1 is composed of engineered pentameric promoters based on C. albicans lumazine synthase assembled with 20 trimeric promoters displaying HA ectodomains. It contains hemagglutinin (HA) proteins from the following 4 influenza strains: A/Idaho/07/2018, A/Perth/1008/2019, B/Colorado/06/2017 and B/Phuket/3073/2013. FluMos-v1 was supplied in a single-use vial at a concentration of 180 mcg/mL.
In Part A, FluMos-v1 was compared to licensed 2020-2021 QIV Flucelvax (Registered Trademark) that was developed by Seqirus, Inc. and formulated with the following 4 influenza strains: A/Hawaii/70/2019 (H1N1) pdm09-like virus, A/Hong Kong/45/2019 (H3N2)-like virus, B/Washington/02/2019-like virus, and B/Phuket/3073/2013-like virus.
In Part B, a higher dose of FluMos-v1 was tested that more closely matches the amount of each HA antigen in Flucelvax. The adjuvant Adjuplex (Registered Trademark) was added to FluMos-v1 to evaluate the potential for increased immunogenicity.
Adjuplex is a sterile, pyrogen-free adjuvant solution produced by the VRC Pilot Plant. Adjuplex comprises highly purified de-oiled soy lecithin and benzene-free carbomer homopolymer formulated in phosphate buffered saline at a pH of 6.5 plus or minus 0.3. Adjuplex was provided as a sterile, pyrogen-free, homogeneous solution filled to 0.7 mL in 3-mL glass vials. Adjuplex was mixed with study products in the pharmacy during preparation prior to vaccination at a 20% dose by volume.
FluMos-v1, FluMos-V1 plus Adjuplex, and Flucelvax were administered intramuscularly (IM) in the deltoid muscle via needle and syringe.
Participants:
A total of 63 participants enrolled as follows:
Part A
Part A, Group 1 (20 mcg FluMos-v1): 5 participants
Group 1A (N=1): Did not receive 2020-2021 season's licensed influenza vaccine at any time prior to enrollment
Group 1B (N=4): Receipt of the 2020-2021 season's licensed influenza vaccine more than 4 months prior to enrollment
Part A, Group 2 (60 mcg FluMos-v1): 15 participants
Group 2A (N=4): Did not receive 2020-2021 season's licensed influenza vaccine at any time prior to enrollment
Group 2B (N=11): Receipt of the 2020-2021 season's licensed influenza vaccine more than 4 months prior to enrollment
Part A, Group 3 (60 mcg Flucelvax®): 15 participants
Group 3A (N=3): Did not receive 2020-2021 season's licensed influenza vaccine at any time prior to enrollment
Group 3B (N=12): Receipt of the 2020-2021 season's licensed influenza vaccine more than 4 months prior to enrollment
Part B
Part B, Group 4 (100 mcg FluMos-v1): 15 participants
Group 4A (N=1): Did not receive 2021-2022 or 2022-2023 season's licensed influenza vaccine at any time prior to enrollment
Group 4B (N=14): Receipt of the 2021-2022 or 2022-2023 season's licensed influenza vaccine more than 4 months prior to enrollment
Part B, Group 5 (100 mcg FluMos-v1 + Adjuplex (20% v/v)): 13 participants
Group 5A (N=2): Did not receive 2021-2022 or 2022-2023 season's licensed influenza vaccine at any time prior to enrollment
Group 5B (N=11): Receipt of the 2021-2022 or 2022-2023 season's licensed influenza vaccine more than 4 months prior to enrollment
Study Plan:
In Part A, the study evaluated the safety, tolerability, and immunogenicity of a single dose of FluMos-v1 vaccine alone in a dose-escalation design.
In Part B, the study evaluated the safety, tolerability, and immunogenicity of a single dose of FluMos-v1 vaccine with or without Adjuplex.
Group 6 and Part C were optional, and a decision was made not to enroll the optional Groups 6-8 in the study.
The protocol required 1 vaccination visit, about 8 follow-up visits, and a telephone contact on the day after vaccination. Solicited reactogenicity were evaluated using a 7-day diary card. Assessment of vaccine safety included clinical observation and monitoring of hematological and chemical parameters at clinical visits throughout the study.
Study Duration:
Participants were evaluated for 40 weeks following vaccine administration including through an influenza season.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 63
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part B, Group 5 (5A-5B): FluMos-v1 (100 mcg) + Adjuplex (20% v/v) VRC-FLUMOS0111-00-VP (FluMos-v1) FluMos-v1 (100 mcg) plus Adjuplex (20% v/v) administered intramuscularly (IM) by needle/syringe Part A, Group 1 (1A-1B): FluMos-v1 (20 mcg) VRC-FLUMOS0111-00-VP (FluMos-v1) FluMos-v1 (20 mcg) administered intramuscularly (IM) by needle/syringe Part A, Group 2 (2A-2B): FluMos-v1 (60 mcg) VRC-FLUMOS0111-00-VP (FluMos-v1) FluMos-v1 (60 mcg) administered intramuscularly (IM) by needle/syringe Part B, Group 4 (4A-4B): FluMos-v1 (100 mcg) VRC-FLUMOS0111-00-VP (FluMos-v1) FluMos-v1 (100 mcg) administered intramuscularly (IM) by needle/syringe Part A, Group 3 (3A-3B): Flucelvax (60 mcg) Flucelvax Licensed QIV Flucelvax (60 mcg) administered intramuscularly (IM) by needle/syringe Part B, Group 5 (5A-5B): FluMos-v1 (100 mcg) + Adjuplex (20% v/v) VRC-GENADJ0110-AP-NV (Adjuplex) FluMos-v1 (100 mcg) plus Adjuplex (20% v/v) administered intramuscularly (IM) by needle/syringe
- Primary Outcome Measures
Name Time Method Number of Participants Reporting Local Reactogenicity Signs and Symptoms Within 7 Days of Product Administration 7 days after product administration Participants recorded the occurrence of solicited local symptoms on a diary card for 7 days after study product administration and reviewed the diary card with clinic staff at a follow up visit. Participants were counted once for each symptom at the worst severity if they indicated experiencing the symptom more than one time at any severity during the reporting period. The number reported for "Any Local Symptom" is the number of participants reporting any local symptom at the worst severity. Reactogenicity grading (Mild, Moderate, Severe) was done using the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials, modified from FDA Guidance - September 2007.
Number of Participants Reporting Systemic Reactogenicity Signs and Symptoms Within 7 Days of Product Administration 7 days after product administration Participants recorded the occurrence of solicited systemic symptoms on a diary card for 7 days after study product administration and reviewed the diary card with clinic staff at a follow up visit. Participants were counted once for each symptom at the worst severity if they indicated experiencing the symptom more than one time at any severity during the reporting period. The number reported for "Any Systemic Symptom" is the number of participants reporting any systemic symptom at the worst severity. Reactogenicity grading (Mild, Moderate, Severe) was done using the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials, modified from FDA Guidance - September 2007.
Number of Participants With Serious Adverse Events (SAEs) Following Product Administration Day 0 after product administration through Day 280, up to Week 40 SAEs were recorded from receipt of product administration through the last study visit at Week 40. The relationship between a SAE and the study product was assessed by the investigator based on clinical judgment and the definitions outlined in the protocol. A participant with multiple experiences of the same event is counted once using the event of worst severity.
Number of Participants With One or More Unsolicited Non-Serious Adverse Events (AEs) Following Product Administration Day 0 through 28 days post product administration, up to Week 4 Unsolicited AEs and attribution assessments were recorded in the study database from receipt of study product administration through the visit scheduled for 4 weeks after study product administration. At other time periods greater than 4 weeks after the study product administration, only serious AEs (SAEs reported as a separate outcome and in the AE module), influenza-like illness (ILI) or influenza and new chronic medical conditions that required ongoing medical management (reported as separate outcomes) were recorded through the last study visit. The relationship between an AE and the study product was assessed by the investigator based on clinical judgment and the definitions outlined in the protocol. A participant with multiple experiences of the same event is counted once using the event of worst severity.
Number of Participants With New Chronic Medical Conditions Following Product Administration Day 0 after product administration through Day 280, up to Week 40 New chronic medical conditions that required ongoing medical management were recorded from receipt of study product administration through the last expected study visit at Week 40. The relationship between a new chronic medical condition and the study product was assessed by the investigator based on clinical judgment and the definitions outlined in the protocol. A participant with multiple experiences of the same event is counted once using the event of worst severity.
Number of Participants With Abnormal Laboratory Measures of Safety Following Product Administration Day 0 through 28 days post product administration, up to Week 4 Abnormal lab results recorded as unsolicited adverse events (AEs) are summarized. Safety lab parameters included hematology (hemoglobin, hematocrit, platelets, and white blood cell (WBC), red blood cell (RBC), neutrophil, lymphocyte, monocyte, eosinophil and basophil percents/counts) and chemistry (alanine aminotransferase (ALT), alanine aspartate (AST), alkaline phosphate (ALP), creatinine and total bilirubin). Complete Blood Count (CBC) with differential, total bilirubin, AST, ALT, and ALP results were collected at Baseline, Day 0, Day 14, and 28. Creatinine results were collected at Baseline, Day 0 and Day 14. Institutional lab normal ranges as well as Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventative Vaccine Clinical Trials FDA Guidance, September 2007 were used.
Number of Participants With Influenza or Influenza-like Illness (ILIs) Following Product Administration Day 0 after product administration through Day 280, up to Week 40 Influenza or influenza-like illness (ILI) were recorded in the study database from receipt of the study product administration through the last study visit. ILI was defined as fever (temperature of 100 degrees F \[37.8 degrees C\] or greater) and a cough and/or sore throat in the absence of a known cause other than influenza. Collection of nasopharyngeal swabs were used for laboratory confirmation of influenza by polymerase chain reaction (PCR) in participants who met criteria for ILI. Subsequently, results of any reported laboratory testing for identification of pathogens were included for cases meeting initial criteria for ILI. The severity of illness in participants with laboratory confirmed influenza illness were captured on a case report form rather than on an Adverse Event (AE) form.
- Secondary Outcome Measures
Name Time Method Antibody Response Following the Completion of Vaccination Baseline to 2 weeks after product administration FluMos-v1-specific antibody titers were measured by Electrochemiluminescence Immunoassay (ECLIA) using a Meso Scale Discovery (MSD) platform. FluMos-v1 was biotinylated at an AviTag site located proximal to the C-terminus from the trimer foldon and bound to MSD streptavidin-coated plates. Serum samples collected at 2 weeks after product administration were assayed alongside healthy pooled human sera (not from this trial) as a reference standard. Binding of the reference standard to FluMos-v1 was assigned a stock concentration of 54000 arbitrary units per milliliter (AU/mL). Serial dilutions of sample within the dynamic range of the standard curve were interpolated to assign a sample concentration in AU/mL. Group geometric mean AU/mL values and 95% confidence intervals are reported.
Trial Locations
- Locations (1)
National Institutes of Health Clinical Center
🇺🇸Bethesda, Maryland, United States