Phase 2 Dose and Formulation Confirmation of Quad-NIV in... | NCT03658629 | Trialant
NCT03658629
Sponsor
Novavax
Status
Terminated
Last Update Posted
Nov 4, 2022Actual
Enrollment
1,375Actual
Phase
Phase 2
Conditions
Influenza, Human
Interventions
NanoFlu (Quad-NIV)
Matrix-M Adjuvant
Placebo
Fluzone HD
Flublok Quadrivalent
Influenza Vaccine
Countries
United States
Protocol Section
Identification Module
NCT ID
NCT03658629
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
qNIV-E-201
Secondary IDs
Not provided
Brief Title
Phase 2 Dose and Formulation Confirmation of Quad-NIV in Older Adults
Official Title
Phase 2 Clinical Trial to Confirm the Dose and Formulation of a Recombinant Quadrivalent Nanoparticle Influenza Vaccine (Quad-NIV) With or Without Matrix-M1™ Adjuvant in Healthy Adults ≥ 65 Years of Age
Acronym
Not provided
Organization
NovavaxINDUSTRY
Status Module
Record Verification Date
Nov 2022
Overall Recruitment Status or Expanded Access Status
Terminated
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
This study was terminated 182 days after initial dosing.
Expanded Access Info
No
Start Date
Sep 24, 2018Actual
Primary Completion Date
Apr 26, 2019Actual
Completion Date
Apr 26, 2019Actual
First Submitted Date
Aug 31, 2018
First Submission Date that Met QC Criteria
Aug 31, 2018
First Posted Date
Sep 5, 2018Actual
Results Waived
Not provided
Results First Submitted Date
Jul 27, 2022
Results First Submitted that Met QC Criteria
Nov 3, 2022
Results First Posted Date
Nov 4, 2022Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Dec 4, 2019
Certification/Extension First Submitted that Passed QC Review
Nov 3, 2022
Certification/Extension First Posted Date
Nov 4, 2022Actual
Last Update Submitted Date
Nov 3, 2022
Last Update Posted Date
Nov 4, 2022Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
NovavaxINDUSTRY
Collaborators
Not provided
Oversight Module
Has Data Monitoring Committee (DMC)
No
Is FDA Regulated Drug
Yes
Is FDA Regulated Device
No
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
Brief Summary
A Phase 2 trial to confirm the dose and formulation, demonstrate adjuvant effect, and evaluate the safety and tolerability of a single intramuscular injection of Quad-NIV with or without Matrix-M1 adjuvant in healthy adults ≥ 65 years of age.
A total of approximately 1375 subjects were to be randomized to seven treatment groups to receive Quad-NIV or an active comparator.
Detailed Description
This randomized, observer-blind, active-controlled, Phase 2 trial was conducted at multiple sites. The composition of the Quad-NIV Influenza Vaccines used in this trial included recombinant H1, H3, and two B hemagglutinin proteins for the 2018-2019 Northern Hemisphere influenza virus strains.
Approximately 1375 healthy male and female subjects ≥ 65 years were randomized into 7 treatment groups (group A to group G), receiving various formulations of Quad-NIV, with or without Matrix-M1 adjuvant or one of two active comparator influenza vaccines. Within each site, randomization was stratified by history of receipt of 2017-2018 influenza vaccine. Subjects received two injections 28 days apart. On Day 0, subjects received one of the five Quad-NIV formulations or one of the two comparator influenza vaccines. On Day 28, subjects received either placebo or a licensed influenza vaccine rescue dose, depending on his or her initial randomization.
Subjects were followed for safety for approximately 6 months, with primary immunogenicity results at Day 28.
Conditions Module
Conditions
Influenza, Human
Keywords
Not provided
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 2
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
1,375Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
Dose A
Experimental
Alternating deltoid injections of Quad-NIV (60 µg HA per A strain and B strain; in-clinic mix with 50 µg of Matrix-M1) on Day 0 and Placebo on Day 28.
Biological: NanoFlu (Quad-NIV)
Other: Matrix-M Adjuvant
Other: Placebo
Dose B
Experimental
Alternating deltoid injections of Quad-NIV (60 µg HA per A strain and B strain; co-formulated with 50 µg of Matrix-M1) on Day 0 and Placebo on Day 28.
Biological: NanoFlu (Quad-NIV)
Other: Matrix-M Adjuvant
Other: Placebo
Dose C
Experimental
Alternating deltoid injections of Quad-NIV (60 µg HA per A strain and B strain; co-formulated with 75 µg of Matrix-M1) on Day 0 and Placebo on Day 28.
Biological: NanoFlu (Quad-NIV)
Other: Matrix-M Adjuvant
Other: Placebo
Dose D
Experimental
Alternating deltoid injections of Quad-NIV (60 µg HA per A strain and 90 µg HA per B strain; co-formulated with 50 µg of Matrix-M1) on Day 0 and Placebo on Day 28.
Adverse Events over the 7 days post-injection; all adverse events (including adverse changes in clinical laboratory parameters) through 21 days post-injection; and Medically Attended Adverse Events (MAEs), Serious Adverse Events (SAEs), and Significant New Medical Conditions (SNMCs) through 6 months post-injection.
Day 0 - Day 182
Hemagglutination Inhibition (HAI) Titers Specific for Vaccine Homologous A and B Influenza Strains Expressed as Geometric Man Titer (GMT)
HAI antibody titers specific for the HA receptor binding domains of vaccine homologous A and B strain(s) at Days 0 and Day 28 post-vaccination expressed as geometric man titer (GMT).
Day 0 - Day 28
HAI Titers Specific for Antigenically-drifted Influenza Strains Expressed as GMT
HAI antibody titers specific for at least 2 antigenically-drifted influenza strains, at Days 0 and 28 post-vaccination expressed as geometric man titer (GMT).
Day 0 - Day 28
Secondary Outcomes
Measure
Description
Time Frame
HAI Titers Specific for Vaccine-homologous A and B Influenza Strains Expressed as GMT
HAI antibody titers specific for the HA receptor binding domains of vaccine-homologous A and B strain(s) expressed as GMT on Day 0,28,56 and 182.
Day 0 - Day 182
HAI Titers Specific for Vaccine-homologous A and B Influenza Strains Expressed as Geometric Mean Fold Ratio (GMFR)
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
Inclusion Criteria:
Clinically-stable adult male or female, ≥ 65 years of age. Subjects may have 1 or more chronic medical diagnoses, but should be clinically stable as assessed by:
Absence of changes in medical therapy within 1 month due to treatment failure or toxicity,
Absence of medical events qualifying as serious adverse events within 2 months; and
Absence of known, current, and life-limiting diagnoses which render survival to completion of the protocol unlikely in the opinion of the investigator.
Willing and able to give informed consent prior to trial enrollment, and
Living in the community and able to attend trial visits, comply with trial requirements, and provide timely, reliable, and complete reports of adverse events.
Exclusion Criteria:
Participation in research involving investigational product (drug / biologic / device) within 45 days before planned date of first injection.
Participation in any previous Novavax's influenza vaccine clinical trial(s).
History of a serious reaction to prior influenza vaccination, known allergy to constituents of licensed comparator vaccines or polysorbate 80.
Received any vaccine in the 4 weeks preceding the trial vaccination and any influenza vaccine within 6 months preceding the trial vaccination.
Any known or suspected immunosuppressive illness, congenital or acquired, based on medical history and/or physical examination.
Chronic administration (defined as more than 14 continuous days) of immunosuppressants or other immune-modifying drugs within 6 months prior to the administration of the trial vaccine. An immunosuppressant dose of glucocorticoid will be defined as a systemic dose ≥ 10 mg of prednisone per day or equivalent. The use of topical, inhaled, and nasal glucocorticoids will be permitted.
Administration of immunoglobulins and/or any blood products within the 3 months preceding the administration of the trial vaccine or during the trial.
Acute disease at the time of enrollment (defined as the presence of a moderate or severe illness with or without fever, or an oral temperature ≥ 38.0°C, on the planned day of vaccine administration).
Any condition that in the opinion of the investigator would pose a health risk to the subject if enrolled or could interfere with evaluation of the vaccine or interpretation of trial results (including neurologic or psychiatric conditions deemed likely to impair the quality of safety reporting).
Known disturbance of coagulation.
Suspicion or recent history (within 1 year of planned vaccination) of alcohol or other substance abuse.
Shinde V, Cai R, Plested J, Cho I, Fiske J, Pham X, Zhu M, Cloney-Clark S, Wang N, Zhou H, Zhou B, Patel N, Massare MJ, Fix A, Spindler M, Thomas DN, Smith G, Fries L, Glenn GM. Induction of Cross-Reactive Hemagglutination Inhibiting Antibody and Polyfunctional CD4+ T-Cell Responses by a Recombinant Matrix-M-Adjuvanted Hemagglutinin Nanoparticle Influenza Vaccine. Clin Infect Dis. 2021 Dec 6;73(11):e4278-e4287. doi: 10.1093/cid/ciaa1673.
Alternating deltoid injections of Quad-NIV (60 µg HA per A strain and B strain; in-clinic mix with 50 µg of Matrix-M1) on Day 0 and Placebo on Day 28.
Alternating deltoid injections of Quad-NIV (60 µg HA per A and B strain without adjuvant) on Day 0 and Licensed 2018-2019 Influenza vaccine on Day 28.
Biological: NanoFlu (Quad-NIV)
Biological: Influenza Vaccine
Dose F
Experimental
Alternating deltoid injections of 2018-2019 High-Dose Trivalent Vaccine on Day 0 and Placebo on Day 28.
Other: Placebo
Biological: Fluzone HD
Dose G
Experimental
Alternating deltoid injections of 2018-2019 Quadrivalent Vaccine on Day 0 and Placebo on Day 28.
HAI antibody titers specific for the HA receptor binding domains of vaccine-homologous A and B strain(s) expressed as GMFR on Day 28,56 and 182.
Day 28 - Day 182
Number of Participants Who Seroconverted as Determined by HAI Titers Specific for Vaccine-homologous A and B Influenza Strains
HAI antibody titers specific for the HA receptor binding domains of vaccine-homologous A and B strain(s) expressed as SCR on Day 28,56 and 182.
Day 28 - Day 182
Number of Participants Who Had Seroprotection as Determined by HAI Titers Specific for Vaccine-homologous A and B Influenza Strains
HAI antibody titers specific for the HA receptor binding domains of vaccine-homologous A and B strain(s) expressed as SPR on Day 28,56 and 182.
Day 28 - Day 182
HAI Titers Specific for Antigenically-drifted Influenza Strains Expressed as GMT
HAI antibody titers specific for antigenically-drifted influenza strains, at Days 0,28, 56 and 182 expressed as geometric man titer (GMT).
Day 0 - Day 182
HAI Titer Responses Specific for Antigenically-drifted Influenza Strains Expressed as GMFR
HAI antibody titer responses specific for antigenically-drifted influenza strains, at Days 28, 56, and 182 expressed as Geometric Fold Ratio.
Day 28 - Day 182
Number of Participants Who Seroconverted as Determined by HAI Titers Specific for Antigenically-drifted Influenza Strains
HAI antibody titers specific for antigenically-drifted influenza strains, at Days 28, 56 and 182 expressed as SCR.
Day 28 - Day 182
Number of Participants Who Had Seroprotection as Determined by HAI Titers of Antigenically-drifted Influenza Strains
HAI antibody titers specific for antigenically-drifted influenza strains, at Days 28, 56 and 182 expressed as SPR.
Day 28 - Day 182
Savannah
Georgia
31406
United States
US013
Stockbridge
Georgia
30281
United States
US138
Rockville
Maryland
20854
United States
US025
Norfolk
Nebraska
68701
United States
US018
Omaha
Nebraska
68134
United States
US078
Cary
North Carolina
27518
United States
US108
Raleigh
North Carolina
27609
United States
US137
Salisbury
North Carolina
28144
United States
US132
Statesville
North Carolina
28625
United States
US071
Wilmington
North Carolina
28401
United States
US063
Winston-Salem
North Carolina
27103
United States
US056
Moncks Corner
South Carolina
29461
United States
US050
Dakota Dunes
South Dakota
57049
United States
Alternating deltoid injections of Quad-NIV (60 µg HA per A strain and B strain; co-formulated with 50 µg of Matrix-M1) on Day 0 and Placebo on Day 28.
FG002
Group C
Alternating deltoid injections of Quad-NIV (60 µg HA per A strain and B strain; co-formulated with 75 µg of Matrix-M1) on Day 0 and Placebo on Day 28.
FG003
Group D
Alternating deltoid injections of Quad-NIV (60 µg HA per A strain and 90 µg HA per B strain; co-formulated with 50 µg of Matrix-M1) on Day 0 and Placebo on Day 28.
FG004
Group E
Alternating deltoid injections of Quad-NIV (60 µg HA per A and B strain without adjuvant) on Day 0 and Licensed 2018-2019 Influenza vaccine on Day 28.
FG005
Group F
Alternating deltoid injections of 2018-2019 High-Dose Trivalent Vaccine on Day 0 and Placebo on Day 28.
FG006
Group G
Alternating deltoid injections of 2018-2019 Quadrivalent Vaccine on Day 0 and Placebo on Day 28.
FG000158 subjects
FG001309 subjects
FG002155 subjects
FG003133 subjects
FG004313 subjects
FG005154 subjects
FG006153 subjects
Participants in Safety Population
FG000157 subjects
FG001305 subjects
FG002156 subjects
FG003132 subjects
FG004311 subjects
FG005153 subjects
FG006151 subjects
COMPLETED
FG000151 subjects
FG001296 subjects
FG002149 subjects
FG003125 subjects
FG004303 subjects
FG005151 subjects
FG006148 subjects
NOT COMPLETED
FG0007 subjects
FG00113 subjects
FG0026 subjects
FG0038 subjects
FG00410 subjects
FG0053 subjects
FG0065 subjects
The population analyzed is the number of participants that are in the Safety Population.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
Quad-NIV Bedside Mix of Antigen and Adjuvant Dose A
Alternating deltoid injections of 2018-2019 Quad-NIV-1 (Day 0) and Placebo (Day 28)
Population analyzed is the number of participants that completed the study. Safety Population
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG00090
BG001179
BG002
Ethnicity (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Hispanic or Latino
BG0006
BG0016
BG002
Race (NIH/OMB)
Population analyzed is the number of participants that completed the study. Safety Population
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
American Indian or Alaska Native
BG0001
BG0010
Type
Title
Description
Population Description
Reporting Status
Anticipated Posting Date
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Time Frame
Units Analyzed
Denominator Units Selected
Arm/Group Information
Denominators
Classes
Analyses
Primary
Number of Subjects With Adverse Events (AEs)
Adverse Events over the 7 days post-injection; all adverse events (including adverse changes in clinical laboratory parameters) through 21 days post-injection; and Medically Attended Adverse Events (MAEs), Serious Adverse Events (SAEs), and Significant New Medical Conditions (SNMCs) through 6 months post-injection.
Safety Population
Posted
Number
participants
Day 0 - Day 182
ID
Title
Description
OG000
Quad-NIV Bedside Mix of Antigen and Adjuvant Dose A
Alternating deltoid injections of 2018-2019 Quad-NIV-1 (Day 0) and Placebo (Day 28)
Hemagglutination Inhibition (HAI) Titers Specific for Vaccine Homologous A and B Influenza Strains Expressed as Geometric Man Titer (GMT)
HAI antibody titers specific for the HA receptor binding domains of vaccine homologous A and B strain(s) at Days 0 and Day 28 post-vaccination expressed as geometric man titer (GMT).
Per-Protocol Population for immunogenicity was used for the primary outcome measure and included all randomized subjects that received the assigned dose of the test article according to protocol, had HAI serology results for Day 0 and Day 28, and had no major protocol deviations affecting the primary immunogenicity outcomes.
Posted
Geometric Mean
95% Confidence Interval
titers
Day 0 - Day 28
ID
Title
Description
OG000
Quad-NIV Bedside Mix of Antigen and Adjuvant Dose A
Alternating deltoid injections of 2018-2019 Quad-NIV-1 (Day 0) and Placebo (Day 28)
HAI Titers Specific for Antigenically-drifted Influenza Strains Expressed as GMT
HAI antibody titers specific for at least 2 antigenically-drifted influenza strains, at Days 0 and 28 post-vaccination expressed as geometric man titer (GMT).
Per-Protocol Population for immunogenicity was used for the primary outcome measure and included all randomized subjects that received the assigned dose of the test article according to protocol, had HAI serology results for Day 0 and Day 28, and had no major protocol deviations affecting the primary immunogenicity outcomes.
Posted
Geometric Mean
95% Confidence Interval
titers
Day 0 - Day 28
ID
Title
Description
OG000
Quad-NIV Bedside Mix of Antigen and Adjuvant Dose A
Alternating deltoid injections of 2018-2019 Quad-NIV-1 (Day 0) and Placebo (Day 28)
HAI Titers Specific for Vaccine-homologous A and B Influenza Strains Expressed as GMT
HAI antibody titers specific for the HA receptor binding domains of vaccine-homologous A and B strain(s) expressed as GMT on Day 0,28,56 and 182.
Per-Protocol Population for immunogenicity was used for this display of secondary outcome measures and included all randomized subjects that received the assigned dose of the test article according to protocol, had HAI serology results for Day 0 and Day 28, and had no major protocol deviations affecting the primary immunogenicity outcomes
Posted
Geometric Mean
95% Confidence Interval
titers
Day 0 - Day 182
ID
Title
Description
OG000
Quad-NIV Bedside Mix of Antigen and Adjuvant Dose A
Alternating deltoid injections of 2018-2019 Quad-NIV-1 (Day 0) and Placebo (Day 28)
HAI Titers Specific for Vaccine-homologous A and B Influenza Strains Expressed as Geometric Mean Fold Ratio (GMFR)
HAI antibody titers specific for the HA receptor binding domains of vaccine-homologous A and B strain(s) expressed as GMFR on Day 28,56 and 182.
Per-Protocol Population for immunogenicity was used for this display of secondary outcome measures and included all randomized subjects that received the assigned dose of the test article according to protocol, had HAI serology results for Day 0 and Day 28, and had no major protocol deviations affecting the primary immunogenicity outcomes
Posted
Geometric Mean
95% Confidence Interval
Fold Ratio
Day 28 - Day 182
ID
Title
Description
OG000
Quad-NIV Bedside Mix of Antigen and Adjuvant Dose A
Alternating deltoid injections of 2018-2019 Quad-NIV-1 (Day 0) and Placebo (Day 28)
Number of Participants Who Seroconverted as Determined by HAI Titers Specific for Vaccine-homologous A and B Influenza Strains
HAI antibody titers specific for the HA receptor binding domains of vaccine-homologous A and B strain(s) expressed as SCR on Day 28,56 and 182.
Per-Protocol Population for immunogenicity was used for this display of secondary outcome measures and included all randomized subjects that received the assigned dose of the test article according to protocol, had HAI serology results for Day 0 and Day 28, and had no major protocol deviations affecting the primary immunogenicity outcomes
Posted
Count of Participants
Participants
Day 28 - Day 182
ID
Title
Description
OG000
Quad-NIV Bedside Mix of Antigen and Adjuvant Dose A
Alternating deltoid injections of 2018-2019 Quad-NIV-1 (Day 0) and Placebo (Day 28)
Number of Participants Who Had Seroprotection as Determined by HAI Titers Specific for Vaccine-homologous A and B Influenza Strains
HAI antibody titers specific for the HA receptor binding domains of vaccine-homologous A and B strain(s) expressed as SPR on Day 28,56 and 182.
Per-Protocol Population for immunogenicity was used for this display of secondary outcome measures and included all randomized subjects that received the assigned dose of the test article according to protocol, had HAI serology results for Day 0 and Day 28, and had no major protocol deviations affecting the primary immunogenicity outcomes
Posted
Number
participants
Day 28 - Day 182
ID
Title
Description
OG000
Quad-NIV Bedside Mix of Antigen and Adjuvant Dose A
Alternating deltoid injections of 2018-2019 Quad-NIV-1 (Day 0) and Placebo (Day 28)
HAI Titers Specific for Antigenically-drifted Influenza Strains Expressed as GMT
HAI antibody titers specific for antigenically-drifted influenza strains, at Days 0,28, 56 and 182 expressed as geometric man titer (GMT).
Per-Protocol Population for immunogenicity was used for this display of secondary outcome measures and included all randomized subjects that received the assigned dose of the test article according to protocol, had HAI serology results for Day 0 and Day 28, and had no major protocol deviations affecting the primary immunogenicity outcomes
Posted
Mean
95% Confidence Interval
titers
Day 0 - Day 182
ID
Title
Description
OG000
Quad-NIV Bedside Mix of Antigen and Adjuvant Dose A
Alternating deltoid injections of 2018-2019 Quad-NIV-1 (Day 0) and Placebo (Day 28)
HAI Titer Responses Specific for Antigenically-drifted Influenza Strains Expressed as GMFR
HAI antibody titer responses specific for antigenically-drifted influenza strains, at Days 28, 56, and 182 expressed as Geometric Fold Ratio.
Per-Protocol Population for immunogenicity was used for this display of secondary outcome measures and included all randomized subjects that received the assigned dose of the test article according to protocol, had HAI serology results for Day 0 and Day 28, and had no major protocol deviations affecting the primary immunogenicity outcomes
Posted
Mean
95% Confidence Interval
Fold Ratio
Day 28 - Day 182
ID
Title
Description
OG000
Quad-NIV Bedside Mix of Antigen and Adjuvant Dose A
Alternating deltoid injections of 2018-2019 Quad-NIV-1 (Day 0) and Placebo (Day 28)
Number of Participants Who Seroconverted as Determined by HAI Titers Specific for Antigenically-drifted Influenza Strains
HAI antibody titers specific for antigenically-drifted influenza strains, at Days 28, 56 and 182 expressed as SCR.
Per-Protocol Population for immunogenicity was used for this display of secondary outcome measures and included all randomized subjects that received the assigned dose of the test article according to protocol, had HAI serology results for Day 0 and Day 28, and had no major protocol deviations affecting the primary immunogenicity outcomes
Posted
Number
participants
Day 28 - Day 182
ID
Title
Description
OG000
Quad-NIV Bedside Mix of Antigen and Adjuvant Dose A
Alternating deltoid injections of 2018-2019 Quad-NIV-1 (Day 0) and Placebo (Day 28)
Number of Participants Who Had Seroprotection as Determined by HAI Titers of Antigenically-drifted Influenza Strains
HAI antibody titers specific for antigenically-drifted influenza strains, at Days 28, 56 and 182 expressed as SPR.
Per-Protocol Population for immunogenicity was used for this display of secondary outcome measures and included all randomized subjects that received the assigned dose of the test article according to protocol, had HAI serology results for Day 0 and Day 28, and had no major protocol deviations affecting the primary immunogenicity outcomes
Posted
Number
participants
Day 28 - Day 182
ID
Title
Description
OG000
Quad-NIV Bedside Mix of Antigen and Adjuvant Dose A
Alternating deltoid injections of 2018-2019 Quad-NIV-1 (Day 0) and Placebo (Day 28)