Randomized, multi-site, dose-escalation study of the safety and immunogenicity of four dosage levels of Intramuscular (IM) Norovirus Bivalent VLP Vaccine adjuvanted with MPL and Al(OH)3 compared to controls. Participants will receive two doses, by IM injection, 28 days apart. The hypotheses for this study are: * The incidence of adverse events after vaccination with IM Norovirus Bivalent VLP Vaccine will be similar to the incidence of adverse events after other IM vaccines including CERVARIX® which contains MPL and Al(OH)3. * Two doses of IM Norovirus Bivalent VLP Vaccine will be more immunogenic than one dose. * The post-vaccination serum antibody responses, the number of antibody secreting cells (ASC), including homing markers, and memory B-cell responses directed against norovirus antigens will be increased after IM Norovirus Bivalent VLP Vaccine compared to controls.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
TRIPLE
Enrollment
102
2 Doses 28 days apart Cohort A: 18-49 Years Cohort A1: IM Norovirus Bivalent GI.1/GII.4 VLP Vaccine (5/5 mcg) Cohort A2: IM Norovirus Bivalent GI.1/GII.4 VLP Vaccine (15/15 mcg) Cohort A3: IM Norovirus Bivalent GI.1/GII.4 VLP Vaccine (50/50 mcg) Cohort A4: IM Norovirus Bivalent GI.1/GII.4 VLP Vaccine (150/150 mcg) Cohort B: 50-64 Years IM Norovirus Bivalent GI.1/GII.4 VLP Vaccine (50/50 mcg) Cohort C: 65-85 Years IM Norovirus Bivalent GI.1/GII.4 VLP Vaccine (50/50 mcg) Cohort D: 18-49 Years IM Norovirus Bivalent GI.1/GII.4 VLP Vaccine (50/50 mcg)
Two doses 28 days apart
Navy Medical Research Center
Silver Springs, Maryland, United States
Saint Louis University
St Louis, Missouri, United States
University of Rochester Medical Center
Rochester, New York, United States
Number of Participants With Solicited Local Adverse Events (AEs) Post Dose 1
The solicited local adverse events were reported using a memory aid. Pain was scaled as Mild (did not interfere with activity); Moderate (repeated use of non-narcotic pain reliever greater than (\>) 24 hours \[24h\] or interfered with activity); and Severe (any use of narcotic pain reliever or prevented daily activity). Tenderness was scaled as Mild (mild discomfort to touch); Moderate (discomfort with movement); and Severe (significant discomfort at rest). Swelling and redness were scaled as Mild (2.5-5 centimeter \[cm\] and did not interfere with activity); Moderate (5.1-10 cm or interfered with activity); and Severe (\>10 cm or prevented daily activity).
Time frame: Day 0 up to Day 7
Number of Participants With Solicited Local AEs Post Dose 2
The solicited local adverse events were reported using a memory aid. Pain was scaled as Mild (did not interfered with activity); Moderate (repeated use of non-narcotic pain reliever \>24h or interfered with activity); and Severe (any use of narcotic pain reliever or prevented daily activity). Tenderness was scaled as Mild (mild discomfort to touch); Moderate (discomfort with movement); and Severe (significant discomfort at rest). Swelling and redness were scaled as Mild (2.5-5 cm and did not interfere with activity); Moderate (5.1-10 cm or interfered with activity); and Severe (\>10 cm or prevented daily activity).
Time frame: Day 28 up to Day 35
Number of Participants With Solicited Systemic AEs Post Dose 1
Elevated oral temperature:Mild(38-38.4 Celsius\[C\]);Moderate(38.5-38.9 C);Severe(39-40 C).Headache:Mild(no interference with activity);Moderate(repeated use of non-narcotic pain reliever\>24h/some interference with activity);Severe(significant;any use of narcotic pain reliever/prevented daily activity).Fatigue,Malaise:Mild(no interference with activity);Moderate(some interference with activity);Severe(significant;prevented daily activity).Diarrhea:Mild(2-3loose stools/\<400gram\[g\]/24h);Moderate(4-5stools/400-800g/24h);Severe(\>=6watery stools/\>800g/24h/required intravenous\[IV\]hydration).Nausea/Vomiting:Mild(no interference with activity/1-2 episodes/24h);Moderate(some interference with activity/\>2 episodes/24h);Severe(prevented daily activity,required IV hydration).Muscle ache,chills,joint ache,abdominal cramp/pain:Mild(no interference with activity);Moderate(some interference with activity,not required medical intervention);Severe(prevented daily activity,required medical intervention).
Time frame: Day 0 up to Day 7
Number of Participants With Solicited Systemic AEs Post Dose 2
Elevated oral temperature:Mild(38-38.4 C);Moderate(38.5-38.9 C);Severe(39-40 C).Headache:Mild(no interference with activity);Moderate(repeated use of non-narcotic pain reliever\>24h/some interference with activity);Severe(significant;any use of narcotic pain reliever/prevented daily activity).Fatigue,Malaise:Mild(no interference with activity);Moderate(some interference with activity);Severe(significant;prevented daily activity).Diarrhea:Mild(2-3loose stools/\<400g/24h);Moderate(4-5stools/400-800g/24h);Severe(\>=6watery stools/\>800g/24h/required IV hydration).Nausea/Vomiting:Mild(no interference with activity/1-2 episodes/24h);Moderate(some interference with activity/\>2 episodes/24h);Severe(prevented daily activity,required IV hydration).Muscle ache,chills,joint ache,abdominal cramp/pain:Mild(no interference with activity);Moderate(some interference with activity,not required medical intervention);Severe(prevented daily activity,required medical intervention).
Time frame: Day 28 up to Day 35
Number of Participants With Unsolicited AEs Post Dose 1
Time frame: Baseline up to Day 28 (Pre-dose 2)
Number of Participants With Unsolicited AEs Post Dose 2
Time frame: Day 28 up to Day 56 (Post dose 2)
Number of Participants With Clinically Significant Change From Baseline in Markedly Abnormal Laboratory Values
The number of participants with any markedly abnormal standard safety laboratory values (serum chemistry or hematology) collected throughout study.
Time frame: Baseline up to Day 35
Number of Participants With Serious Adverse Events (SAEs), Onset of Significant New Medical Conditions, Including Adverse Events of Special Interest (AESI)
Time frame: Baseline up to 365 Days after post dose 2 (Day 393)
Geometric Mean Titer (GMT) of Serum Anti-norovirus GI.1 and GII.4 VLP Ig (Immunoglobulin) A
Run I was defined as the initial analysis performed once Day 56 post dose data was available. Run II was defined as final analysis performed after all later time points were achieved.
Time frame: First (I) run: predose 1 and 7, 21, 28 days postdose (PD)1, and 7 and 28 days PD2; second (II) run: predose 1 and 28, 152 and 365 days PD2 (up to Day 393)
GMT of Serum Anti-norovirus GI.1 and GII.4 VLP IgG
Run I was defined as the initial analysis performed once Day 56 post dose data was available. Run II was defined as final analysis performed after all later time points were achieved.
Time frame: I run: predose 1 and 7, 21, 28 days PD1, and 7 and 28 days PD2; II run: predose 1 and 28, 152 and 365 days PD2 (up to Day 393)
GMT of Serum Anti-norovirus GI.1 and GII.4 VLP IgM
Run I was defined as the initial analysis performed once Day 56 post dose data was available. Run II was defined as final analysis performed after all later time points were achieved.
Time frame: I run: predose 1 and 7, 21, 28 days PD1, and 7 and 28 days PD2; II run: predose 1 and 28, 152 and 365 days PD2 (up to Day 393)
Geometric Mean Fold Rise (GMFR) of Serum Anti-norovirus GI.1 and GII.4 VLP IgA as Compared to Baseline
Run I was defined as the initial analysis performed once Day 56 post dose data was available. Run II was defined as final analysis performed after all later time points were achieved.
Time frame: I run: 7, 21, 28 days PD1, 7 and 28 days PD2; II run: 28, 152 and 365 days PD2 (up to Day 393)
GMFR of Serum Anti-norovirus GI.1 and GII.4 VLP IgG as Compared to Baseline
Run I was defined as the initial analysis performed once Day 56 post dose data was available. Run II was defined as final analysis performed after all later time points were achieved.
Time frame: I run: 7, 21, 28 days PD1, 7 and 28 days PD2; II run: 28, 152 and 365 days PD2 (up to Day 393)
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
GMFR of Serum Anti-norovirus GI.1 and GII.4 VLP IgM as Compared to Baseline
Run I was defined as the initial analysis performed once Day 56 post dose data was available. Run II was defined as final analysis performed after all later time points were achieved.
Time frame: I run: 7, 21, 28 days PD1, 7 and 28 days PD2; II run: 28, 152 and 365 days PD2 (up to Day 393)
Percentage of Participants With Seroresponse for Serum Anti-norovirus GI.1 and GII.4 VLP IgA
Seroresponse was defined as a 4-fold increase in antibody titer compared to pre-immunization titers. Run I was defined as the initial analysis performed once Day 56 post dose data was available. Run II was defined as final analysis performed after all later time points were achieved.
Time frame: I run: 7, 21, 28 days PD1, 7 and 28 days PD2; II run: 28, 152 and 365 days PD2 (up to Day 393)
Percentage of Participants With Seroresponse for Serum Anti-norovirus GI.1 and GII.4 VLP IgG
Seroresponse was defined as a 4-fold increase in antibody titer compared to pre-immunization titers. Run I was defined as the initial analysis performed once Day 56 post dose data was available. Run II was defined as final analysis performed after all later time points were achieved.
Time frame: I run: 7, 21, 28 days PD1, 7 and 28 days PD2; II run: 28, 152 and 365 days PD2 (up to Day 393)
Percentage of Participants With Seroresponse for Serum Anti-norovirus GI.1 and GII.4 VLP IgM
Seroresponse was defined as a 4-fold increase in antibody titer compared to pre-immunization titers. Run I was defined as the initial analysis performed once Day 56 post dose data was available. Run II was defined as final analysis performed after all later time points were achieved.
Time frame: I run: 7, 21, 28 days PD1, 7 and 28 days PD2; II run: 28, 152 and 365 days PD2 (up to Day 393)
GMT of Anti-norovirus GI.1 and GII.4 VLP IgA, IgG, and IgM Combined Using Pan-Ig Enzyme-Linked Immunosorbent Assay (ELISA)
GMTs were assessed for Anti-norovirus GI.1 and GII.4 VLP by Pan-Ig ELISA. A pan ELISA assay captured IgG, IgA and IgM combined. Run I was defined as the initial analysis performed once Day 56 post dose data was available. Run II was defined as final analysis performed after all later time points were achieved.
Time frame: I run: predose 1, 7, 21, 28 days PD1, 7 and 28 days PD2; II run: predose 1, 28, 152 and 365 days PD2 (up to Day 393)
GMFR of Anti-norovirus GI.1 and GII.4 VLP IgA, IgG, and IgM Combined Using Pan-Ig ELISA as Compared to Baseline
GMFRs in GMTs of Anti-norovirus GI.1 and GII.4 VLP by Pan-Ig ELISA. A pan ELISA assay captured IgG, IgA and IgM combined. Run I was defined as the initial analysis performed once Day 56 post dose data was available. Run II was defined as final analysis performed after all later time points were achieved.
Time frame: I run: 7, 21, 28 days PD1, 7 and 28 days PD2; II run: 28, 152 and 365 days PD2 (up to Day 393)
Percentage of Participants With Seroresponse (4-Fold Rise) of Anti-norovirus GI.1 and GII.4 VLP IgA, IgG, and IgM Combined Using Pan-Ig ELISA
Seroresponse was defined as a 4-fold increase in antibody titer compared to pre-immunization titers. Run I was defined as the initial analysis performed once Day 56 post dose data was available. Run II was defined as final analysis performed after all later time points were achieved.
Time frame: I run: 7, 21, 28 days PD1, 7 and 28 days PD2; II run: 28, 152 and 365 days PD2 (up to Day 393)