NCT04622592|CompletedPhase 1ResultsDMCFDA Drug

Adjuvanted Seasonal Recombinant Quadrivalent Virus-Like Particles (QVLP) Influenza Vaccine in Adults 65 Years of Age and Older

A Randomized, Partially-Blinded, Active Comparator-Controlled, Dose-Ranging, Safety, Tolerability, and Immunogenicity Phase 1/2 Study of an Adjuvanted Seasonal Recombinant Quadrivalent VLP Influenza Vaccine in Adults 65 Years of Age and Older

Medicago ClinicalTrials.gov

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1 other identifier

CP-PRO-AdjQVLP-020

Study Type

interventional

Target

209

Locations

1 country

Sites

Timeline

RegisteredNov 2020

StartedNov 2020

CompletionApr 2022

Brief Summary

This randomized, partially-blinded, active comparator-controlled was conducted at multiple sites globally. The composition of QVLP used in this study includes a mix of recombinant H1, H3, and two B hemagglutinin proteins expressed as VLPs and is based on the 2020-2021 influenza virus strains. In this study, 3 dose levels (15 μg/strain, 30 μg/strain, and 45 μg/strain) of QVLP were planned to be tested in combination with 2 dose levels of AS03 adjuvant (full and half dose) in a single-dose regimen to select a dose level of QVLP and adjuvant dose level-combination that is safe and effective for further development. Participants participated in this study for up to approximately 13 months, during which the first visit was scheduled for screening (up to 7 days in advance of vaccine administration) and the second visit on Day 0 was scheduled for vaccine administration. Telephone contacts were made on Day 1, Day 8, and monthly (starting after Day 28) until the end of the study for safety assessments, including concomitant medication use review. Blood draws at the clinic site for key safety assessments were made on Day 3, and Day 28 and for key immunogenicity assessments on Day 0, Day 28, Day 182 (6-month follow-up), and Day 365 (12-month follow-up).

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

209

participants targeted

Target at P75+ for phase_1

Timeline

Completed

Started Nov 2020

Geographic Reach

1 country

14 active sites

Status

completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

1.5 years study duration

First Submitted

Initial submission to the registry

October 16, 2020

Completed

17 days until next milestone

Study Start

First participant enrolled

November 2, 2020

Completed

8 days until next milestone

First Posted

Study publicly available on registry

November 10, 2020

Completed

1.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 26, 2022

Completed

Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

April 26, 2022

Completed

1.2 years until next milestone

Results Posted

Study results publicly available

July 21, 2023

Completed

Last Updated

July 21, 2023

Status Verified

July 1, 2023

Enrollment Period

1.5 years

First QC Date

October 16, 2020

Results QC Date

May 29, 2023

Last Update Submit

July 13, 2023

Conditions

Influenza

Keywords

vaccinesafetyimmunogenicityplant-madevirus-like particlehemagglutinin

Outcome Measures

Primary Outcomes (34)

Geometric Mean Titers (GMTs) of Hemagglutination Inhibition (HI) Antibody Response for Each Homologous Influenza Strain on Day 0
The GMTs in each treatment group were measured using an HI assay for the homologous influenza strains: A/Hawaii/70/2019 (H1N1), A/Minnesota/41/2019 (H3N2), B/Singapore/INFKK-16-0569/2016 (B/Yamagata lineage), and B/Washington/02/2019 (B/Victoria lineage).
Day 0 (pre-vaccination)
GMTs of HI Antibody Response for Each Homologous Influenza Strain on Day 28
The GMTs in each treatment group were measured using an HI assay for the homologous influenza strains: A/Hawaii/70/2019 (H1N1), A/Minnesota/41/2019 (H3N2), B/Singapore/INFKK-16-0569/2016 (B/Yamagata lineage), and B/Washington/02/2019 (B/Victoria lineage).
Day 28
Percentage of Participants With Seroconversion Measured by HI Antibody Response for Each Homologous Influenza Strain on Day 28
Seroconversion rate: the percentage of participants in a given treatment group with either a ≥4-fold increase in reciprocal HI titers between Day 0 and Day 28 or a rise of undetectable HI titer (i.e. \< 10) pre-vaccination (Day 0) to an HI titer of ≥ 40 on Day 28 was measured using an HI assay for the homologous influenza strains A/Hawaii/70/2019 (H1N1), A/Minnesota/41/2019 (H3N2), B/Singapore/INFKK-16-0569/2016 (B/Yamagata lineage), and B/Washington/02/2019 (B/Victoria lineage).
Day 0 (pre-vaccination) up to Day 28
Percentage of Participants With Seroprotection Measured by HI Antibody Response for Each Homologous Influenza Strain on Day 28
Seroprotection rate: the percentage of participants in a given treatment group attaining a reciprocal HI titer of ≥40 on Day 28 (the percentage of vaccine recipients with a serum HI titer of at least 1:40 following vaccination) for the homologous influenza strains A/Hawaii/70/2019 (H1N1), A/Minnesota/41/2019 (H3N2), B/Singapore/INFKK-16-0569/2016 (B/Yamagata lineage), and B/Washington/02/2019 (B/Victoria lineage).
Day 0 (pre-vaccination) up to Day 28
Geometric Mean Fold Rise (GMFR) Measured by HI Antibody Response for Each Homologous Influenza Strain (Day 28/Day 0)
GMFR, the geometric mean of the ratio of GMTs (Day 28/Day 0) in each treatment group was measured using an HI assay for the homologous strains: A/Hawaii/70/2019 (H1N1), A/Minnesota/41/2019 (H3N2), B/Singapore/INFKK-16-0569/2016 (B/Yamagata lineage), and B/Washington/02/2019 (B/Victoria lineage).
Day 0 (pre-vaccination), Day 28
Number of Participants With at Least One Immediate Adverse Event (AE)
An AE is defined as any untoward medical occurrence in a participant who was administered a pharmaceutical product, with or without a causal relationship with the treatment. An AE can be any favorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not related to a medicinal product. Immediate AEs were defined as any solicited (local and systemic) and unsolicited AEs that started up to 30 minutes after vaccination. Solicited local AEs included erythema, swelling, and pain at the injection site. Solicited systemic AEs included fever, headache, fatigue, muscle aches, joint aches, chills, a feeling of general discomfort, swelling in the axilla, and swelling in the neck.
Up to 30 minutes post-vaccination
Number of Participants With at Least One Immediate AE of Grade 1, 2, 3, or 4
An AE is defined as any untoward medical occurrence in a participant who was administered a pharmaceutical product, with or without a causal relationship with the treatment. An AE can be any favorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not related to a medicinal product. Immediate AEs were defined as any solicited (local and systemic) and unsolicited AEs that started up to 30 minutes after vaccination. Solicited local AEs included erythema, swelling, and pain at the injection site. Solicited systemic AEs included fever, headache, fatigue, muscle aches, joint aches, chills, a feeling of general discomfort, swelling in the axilla, and swelling in the neck. The intensity of the AEs was graded according to the United States Food and Drug Administration Toxicity Grading Scale: mild (Grade 1), moderate (Grade 2), severe (Grade 3), or potentially life threatening (Grade 4).
Up to 30 minutes post-vaccination
Number of Participants With at Least One Immediate AE Related to Vaccination
An AE is defined in OM #6. Immediate AEs were defined as any solicited (local and systemic) and unsolicited AEs that started up to 30 minutes after vaccination. Solicited local AEs included erythema, swelling and pain at the injection site. Solicited systemic AEs included fever, headache, fatigue, muscle aches, joint aches, chills, a feeling of general discomfort, swelling in the axilla, and swelling in the neck. A related AE is an event where the investigator determined that the relationship to study vaccine was "Possibly Related", "Probably Related" or "Definitely Related". If a participant reported multiple occurrences of the same AE, only the most closely related occurrence was presented. The causal relationship of all solicited local and systemic AEs was considered related to vaccination. Participants with any related AE was reported.
30 minutes post-vaccination
Number of Participants With at Least One Solicited Local or Systemic AE From Day 0 up to Day 7
An AE is defined as any untoward medical occurrence in a participant who was administered a pharmaceutical product, with or without a causal relationship with the treatment. An AE can be any favorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not related to a medicinal product. Solicited local AEs included erythema, swelling, and pain at the injection site. Solicited systemic AEs included fever, headache, fatigue, muscle aches, joint aches, chills, a feeling of general discomfort, swelling in the axilla, and swelling in the neck.
Day 0 (pre-vaccination) up to Day 7
Number of Participants With at Least One Solicited Local or Systemic AE of Grade 1, 2, 3, or 4 From Day 0 up to Day 7
An AE is defined as any untoward medical occurrence in a participant who was administered a pharmaceutical product, with or without a causal relationship with the treatment. An AE can be any favorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not related to a medicinal product. Solicited local AEs included erythema, swelling and pain at the injection site. Solicited systemic AEs included fever, headache, fatigue, muscle aches, joint aches, chills, a feeling of general discomfort, swelling in the axilla, and swelling in the neck. The intensity of the AEs was graded according to the FDA Toxicity Grading Scale: mild (Grade 1), moderate (Grade 2), severe (Grade 3), or potentially life threatening (Grade 4).
Day 0 (pre-vaccination) up to Day 7
Number of Participants With at Least One Unsolicited AE From Day 0 up to Day 28
An AE is defined as any untoward medical occurrence in a participant who was administered a pharmaceutical product, with or without a causal relationship with the treatment. An AE can be any favorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not related to a medicinal product.
Day 0 (pre-vaccination) up to Day 28
Number of Participants With at Least One Unsolicited AE of Grade 1, 2, 3, or 4 From Day 0 up to Day 28
An AE is defined as any untoward medical occurrence in a participant who was administered a pharmaceutical product, with or without a causal relationship with the treatment. An AE can be any favorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not related to a medicinal product. The intensity of the AEs was graded according to the FDA Toxicity Grading Scale: mild (Grade 1), moderate (Grade 2), severe (Grade 3), or potentially life threatening (Grade 4).
Day 0 (pre-vaccination) up to Day 28
Number of Participants With at Least One Unsolicited AE Related to Vaccination From Day 0 up to Day 28
An AE is defined as any untoward medical occurrence in a participant who was administered a pharmaceutical product, with or without a causal relationship with the treatment. An AE can be any favorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not related to a medicinal product. A related AE was an event where the Investigator determined that the relationship to study vaccine was "Possibly Related", "Probably Related" or "Definitely Related". If a participant reported multiple occurrences of the same AE, only the most closely related occurrence was presented. Participants with any related AE were reported.
Day 0 (pre-vaccination) up to Day 28
Number of Participants With at Least One Serious Adverse Events (SAE) From Day 1 up to Day 28
An AE is defined as any untoward medical occurrence in a participant who was administered a pharmaceutical product, with or without a causal relationship with the treatment. An AE can be any favorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not related to a medicinal product. An SAE is an AE that results in death, is life threatening, results in a persistent or significant disability or incapacity, results in or prolongs an existing hospitalization, is a congenital anomaly or birth defect, or is another important medical event.
Day 1 up to Day 28
Number of Participants With at Least One AE Leading to Withdrawal From the Study From Day 1 up to Day 28
An AE is defined as any untoward medical occurrence in a participant who was administered a pharmaceutical product, with or without a causal relationship with the treatment. An AE can be any favorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not related to a medicinal product.
Day 1 up to Day 28
Number of Participants With at Least One Adverse Event of Special Interest (AESI) From Day 1 up to Day 28
An AE is defined as any untoward medical occurrence in a participant who was administered a pharmaceutical product, with or without a causal relationship with the treatment. An AE can be any favorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not related to a medicinal product. AESIs included hypersensitivity reactions, narcolepsy, Potential Immune-Mediated Diseases (pIMDs), and other AESIs. Participants with any AESI were reported.
Day 1 up to Day 28
Number of Participants With at Least One Medically Attended AE (MAAE) From Day 1 up to Day 28
An AE is defined as any untoward medical occurrence in a participant who was administered a pharmaceutical product, with or without a causal relationship with the treatment. An AE can be any favorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not related to a medicinal product. MAAEs are defined as symptoms or illnesses requiring hospitalization, or emergency room visit, or visit to/by a healthcare provider.
Day 1 up to Day 28
Number of Participants With at Least One New Onset Clinical Disease (NOCD) From Day 1 up to Day 28
All NOCDs that may plausibly have an allergic, autoimmune or inflammatory component were assessed and reported. Plausibility was interpreted broadly; the only clear exceptions were degenerative conditions such as osteoarthritis, age-related physiologic changes and life-style diseases. In this context, most cancers, cardiac conditions, and kidney diseases had to be reported.
Day 1 up to Day 28
Number of Participants With the Occurrence of Death From Day 1 up to Day 28
The number of participants in each treatment group with an occurrence of death was assessed.
Day 1 up to Day 28
Number of Participants With at Least One SAE From Day 29 up to Day 182
An AE is defined as any untoward medical occurrence in a participant who was administered a pharmaceutical product, with or without a causal relationship with the treatment. An AE can be any favorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not related to a medicinal product. An SAE is an AE that results in death, is life threatening, results in a persistent or significant disability or incapacity, results in or prolongs an existing hospitalization, is a congenital anomaly or birth defect, or is another important medical event.
Day 29 up to Day 182
Number of Participants With at Least One AE Leading to Withdrawal From the Study From Day 29 up to Day 182
An AE is defined as any untoward medical occurrence in a participant who was administered a pharmaceutical product, with or without a causal relationship with the treatment. An AE can be any favorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not related to a medicinal product. The number of participants with at least one AE leading to withdrawal was assessed.
Day 29 up to Day 182
Number of Participants With at Least One AESI From Day 29 up to Day 182
An AE is defined as any untoward medical occurrence in a participant who was administered a pharmaceutical product, with or without a causal relationship with the treatment. An AE can be any favorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not related to a medicinal product. AESIs included hypersensitivity reactions, narcolepsy, pIMDs, and other AESIs. Participants with any AESI were reported.
Day 29 up to Day 182
Number of Participants With at Least One MAAE From Day 29 up to Day 182
An AE is defined as any untoward medical occurrence in a participant who was administered a pharmaceutical product, with or without a causal relationship with the treatment. An AE can be any favorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not related to a medicinal product. MAAEs are defined as symptoms or illnesses requiring hospitalization, or emergency room visit, or visit to/by a health care provider.
Day 29 up to Day 182
Number of Participants With at Least One New NOCD From Day 29 up to Day 182
All NOCDs that may plausibly have an allergic, autoimmune or inflammatory component were assessed and reported. Plausibility was interpreted broadly; the only clear exceptions were degenerative conditions such as osteoarthritis, age-related physiologic changes and life-style diseases. In this context, most cancers, cardiac conditions, and kidney diseases were reported.
Day 29 up to Day 182
Number of Participants With an Occurrence of Death From Day 29 up to Day 182
The number of participants in each treatment group with an occurrence of death was assessed.
Day 29 up to Day 182
Number of Participants With at Least One SAE From Day 183 up to Day 365
An AE is defined as any untoward medical occurrence in a participant who was administered a pharmaceutical product, with or without a causal relationship with the treatment. An AE can be any favorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not related to a medicinal product. An SAE is an AE that results in death, is life threatening, results in a persistent or significant disability or incapacity, results in or prolongs an existing hospitalization, is a congenital anomaly or birth defect, or is another important medical event.
Day 183 up to the end of study (Day 365)
Number of Participants With at Least One AE Leading to Withdrawal From the Study From Day 183 up to Day 365
An AE is defined as any untoward medical occurrence in a participant who was administered a pharmaceutical product, with or without a causal relationship with the treatment. An AE can be any favorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not related to a medicinal product. The number of participants with at least one AE leading to withdrawal was assessed.
Day 183 up to the end of study (Day 365)
Number of Participants With at Least One AESI From Day 183 up to Day 365
An AE is defined as any untoward medical occurrence in a participant who was administered a pharmaceutical product, with or without a causal relationship with the treatment. An AE can be any favorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not related to a medicinal product. AESIs included hypersensitivity reactions, narcolepsy, pIMDs, and other AESIs. Participants with any AESI were reported.
Day 183 up to the end of study (Day 365)
Number of Participants With at Least One MAAE From Day 183 up to Day 365
An AE is defined as any untoward medical occurrence in a participant who was administered a pharmaceutical product, with or without a causal relationship with the treatment. An AE can be any favorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not related to a medicinal product. MAAEs were defined as symptoms or illnesses requiring hospitalization, or emergency room visit, or visit to/by a health care provider.
Day 183 up to the end of study (Day 365)
Number of Participants With at Least One NOCD From Day 183 up to Day 365
All NOCDs that may plausibly have an allergic, autoimmune or inflammatory component were assessed and reported. Plausibility should be interpreted broadly; the only clear exceptions are degenerative conditions such as osteoarthritis, age-related physiologic changes and life-style diseases. In this context, most cancers, cardiac conditions, and kidney diseases should be reported.
Day 183 up to the end of study (Day 365)
Number of Participants With an Occurrence of Death From Day 183 up to Day 365
The number of participants in each treatment group with an occurrence of death was assessed.
Day 183 up to the end of study (Day 365)
Number of Participants With Clinically Significant Abnormal Urine, Hematological, and Blood Biochemistry Values on Day 0
Participants were monitored for any abnormal findings in urine parameters (urine color, glucose, occult blood, protein, specific gravity, specimen appearance, pH), hematological parameters (basophils, leukocytes, eosinophils, erythrocytes mean corpuscular hemoglobin, erythrocytes, hematocrit, hemoglobin, lymphocytes, mean platelet volume, monocytes, neutrophils, platelets), and blood chemistry parameters (alanine aminotransferase, albumin, alkaline phosphatase, aspartate aminotransferase, bilirubin, calcium, chloride, cholesterol, creatinine, gamma glutamyl transferase, glucose, HDL and LDL cholesterol, phosphate, potassium, protein, sodium, triglycerides, urea nitrogen). Any laboratory result outside of the testing laboratory's normal range was classified as "clinically significant" or "not clinically significant" by the site investigator, with appropriate documentation.
Day 0 (pre-vaccination)
Number of Participants With Clinically Significant Abnormal Urine, Hematological, and Blood Biochemistry Values on Day 3
Participants were monitored for any abnormal findings in urine parameters (urine color, glucose, occult blood, protein, specific gravity, specimen appearance, pH), hematological parameters (basophils, leukocytes, eosinophils, erythrocytes mean corpuscular hemoglobin, erythrocytes, hematocrit, hemoglobin, lymphocytes, mean platelet volume, monocytes, neutrophils, platelets), and blood chemistry parameters (alanine aminotransferase, albumin, alkaline phosphatase, aspartate aminotransferase, bilirubin, calcium, chloride, cholesterol, creatinine, gamma glutamyl transferase, glucose, HDL and LDL cholesterol, phosphate, potassium, protein, sodium, triglycerides, urea nitrogen). Any laboratory result outside of the testing laboratory's normal range was classified as "clinically significant" or "not clinically significant" by the site investigator, with appropriate documentation.
Day 3
Number of Participants With Clinically Significant Abnormal Urine, Hematological, and Blood Biochemistry Values on Day 28
Participants were monitored for any abnormal findings in urine parameters (urine color, glucose, occult blood, protein, specific gravity, specimen appearance, and pH), hematological parameters (basophils, leukocytes, eosinophils, erythrocytes mean corpuscular hemoglobin, erythrocytes, hematocrit, hemoglobin, lymphocytes, mean platelet volume, monocytes, neutrophils, and platelets), and blood chemistry parameters (alanine aminotransferase, albumin, alkaline phosphatase, aspartate aminotransferase, bilirubin, calcium, chloride, cholesterol, creatinine, gamma glutamyl transferase, glucose, cholesterol, phosphate, potassium, protein, sodium, triglycerides, and urea nitrogen). Any laboratory result outside of the testing laboratory's normal range was classified as "clinically significant" or "not clinically significant" by the site investigator, with appropriate documentation.
Day 28

Secondary Outcomes (39)

GMTs of HI Antibody Response for Each Homologous Influenza Strain on Day 182 and Day 365
Day 182, Day 365
Percentage of Participants With Seroconversion Measured by HI Antibody Response for Each Homologous Influenza Strain on Day 182 and Day 365
Day 0 (pre-vaccination) up to Day 182 and up to Day 365
Percentage of Participants With Seroprotection Measured by HI Antibody Response for Each Homologous Influenza Strain on Day 182 and Day 365
Day 0 (pre-vaccination) up to Day 182 and up to Day 365
GMFR Measured by HI Antibody Response for Each Homologous Influenza Strain (Day 182/Day 0 and Day 365/Day 0)
Day 0 (pre-vaccination), Day 182, Day 365
GMTs of HI Antibody Response for Each Heterologous Influenza Strain
Day 0 (pre-vaccination), Day 28
+34 more secondary outcomes

Study Arms (8)

QVLP15+Full AS03

EXPERIMENTAL

Participants received one intramuscular (IM) injection (total volume 0.7 mL) of 15 μg/strain of the Quadrivalent virus-like particle (VLP) Influenza Vaccine adjuvanted with full dose of AS03 on Day 0 into the deltoid region of the non-dominant arm (if possible).