This study will be conducted in 2 phases. Phase 1 designed to evaluate safety, tolerability and immunogenicity COVID-19 vaccine (NDV-HXP-S) administered at different doses levels (1, 3, and 10 µg) without adjuvant, and at two different dose levels (1 and 3 µg) with the adjuvant CpG 1018 among healthy adults, (age 18-59 years) (210 subjects). Subjects will receive 2 doses of assigned investigational product (IP) on D1 and D29 (V1 and V3), and be assessed in clinic for safety and reactogenicity at 7 days after each vaccination (day 1 as day vaccination). An interim analysis of Phase 1 data will be conducted as the basis for decisions about advancement to Phase 2 of the study and about treatment group down selection. Phase 2 (250 subjects) will include approximately one-third subjects with age 60-75 years.
This study (GPO NDV-HXP-S) will be conducted in 2 phases. Phase 1 will evaluate the safety, tolerability and immunogenicity COVID-19 vaccine (NDV-HXP-S) administered at different doses levels (1, 3, and 10 µg) without adjuvant, and at two different dose levels (1 and 3 µg) with the adjuvant CpG 1018 among healthy adults, (age 18-59 years, 210 subjects). NDV-HXP-S or placebo (0.9% normal saline for injection) will administer IM according to a repeat vaccination schedule (given 28 days apart). In addition, as exploratory objectives, a total of 36 subjects will be randomly selected (1:1:1 ratio) from placebo and two high-dose groups i.e., NDV-HXP-S 10 µg and NDV-HXP-S 3 µg + CpG 1018, to provide additional blood at V1, V5 and V7 for assessment of T-cell-mediated immunity (CMI). An interim analysis of Phase 1 data will be conducted as the basis for decisions about advancement to Phase 2 of the study and about treatment group down selection. In the Phase 2 study, 250 subjects aged 18-75 years will be randomized (1:2:2) to placebo (0.9% normal saline for injection), or one of two selected formulations of NDV HXP S being evaluated in Phase 1 will be enrolled to Phase 2 study. Twelve subjects in each of the three Phase 2 groups (distributed among the two age strata) will be randomized to provide additional blood at V1, V5 and V7 for assessment of T-cell-mediated immunity (CMI). Unblinding will be done as per specific SOP provided by Sponsor. The PI will be expected to provide a rationale for the necessity of unblinding, based on the expectation that knowledge of the subject's treatment assignment will have a meaningful impact on the subject's medical care in the short term. If a subject's treatment assignment is unblinded, the subject will remain in the study and continue with protocol-defined study visits and procedures, unless there is another reason for subject discontinuation. Scheduled unblinding regarding safety concern during severe COVID-19 situation: The elderly subjects (60-75 years) who received placebo will be unblinded and discontinued as soon as COVID-19 vaccine (AstraZeneca) become available from Sponsor. If unblinding is occurred before complete enrollment of 75 elderly subjects, the randomization assignment will be skipped in placebo arm. Therefore, no further subjects will be randomly assigned to receive placebo after unblinding.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
DOUBLE
Enrollment
455
0.9% normal saline for injection
Vaccine NDV-HXP-S, manufactured by GPO with or without adjuvant CpG1018.
Vaccine Trial Centre, Faculty of Tropical Medicine, Mahidol University
Bangkok, Thailand
Frequency of solicited reportable local adverse event after first vaccination
Frequency of solicited reportable local adverse events (pain or tenderness, erythema, swelling or induration) of first vaccination
Time frame: Day 1 up to Day 7 after first vaccination
Frequency of solicited reportable local adverse event after second vaccination
Frequency of solicited reportable local adverse events (pain or tenderness, erythema, swelling or induration) of second vaccination
Time frame: Day 1 up to Day 7 after second vaccination
Frequency of solicited reportable systemic adverse event after first vaccination
Frequency of solicited reportable systemic adverse events (fever, headache,fatigue or malaise, myalgia, arthralgia,nausea or vomitting) of first vaccination
Time frame: Day 1 up to Day 7 after first vaccination
Frequency of solicited reportable systemic adverse event after second vaccination
Frequency of solicited reportable systemic adverse events (fever, headache,fatigue or malaise, myalgia, arthralgia,nausea or vomitting) of second vaccination
Time frame: Day 1 up to Day 7 after second vaccination
Measurement of hemoglobin changed from baseline at 7 days after first and second vaccination
Measurement of hemoglobin (g/dl) changed from baseline at 7 days after first and second vaccination
Time frame: Day 8, Day 36
Measurement of white blood cells changed from baseline at 7 days after first and second vaccination
Measurement of white blood cells (10\^3 cells/ul) changed from baseline at 7 days after first and second vaccination
Time frame: Day 8, Day 36
Measurement of platelet count changed from baseline at 7 days after first and second vaccination
Measurement of platelet count (10\^3 cells/ul) changed from baseline at 7 days after first and second vaccination
Time frame: Day 8, Day 36
Measurement of creatinine changed from baseline at 7 days after first and second vaccination
Measurement of creatinine (mg/dl) changed from baseline at 7 days after first and second vaccination
Time frame: Day 8, Day 36
Measurement of AST changed from baseline at 7 days after first and second vaccination
Measurement of AST (U/L) changed from baseline at 7 days after first and second vaccination
Time frame: Day 8, Day 36
Measurement of ALT change from baseline at 7 days after first and second vaccination
Measurement of ALT (U/L) change from baseline at 7 days after first and second vaccination
Time frame: Day 8, Day 36
Measurement of total bilirubin changed from baseline at 7 days after first and second vaccination
Measurement of total bilirubin (mg/dl) change from baseline at 7 days after first and second vaccination
Time frame: Day 8, Day 36
Frequency of all unsolicited AEs
Frequency of all unsolicited AEs
Time frame: Day 1 up to Day 56
Frequency of SAEs
Frequency of SAEs throughout the entire study period
Time frame: Day 1 up to Day 365
Frequency of medically-attended adverse event (MAAEs)
Frequency of medically-attended adverse event (MAAEs) throughout the entire study period
Time frame: Day 1 up to Day 365
Frequency of AESI
Frequency of AESI throughout the entire study period, including AESI relevant to COVID-19, and potential immune-mediated medical conditions (PIMMC) presented as number and percentage
Time frame: Day 1 up to Day 365
GMT Neutralizing antibody titer 50 changed from baseline after vaccination
GMT Neutralizing antibody titer 50 changed from baseline after vaccination
Time frame: Day 29, Day 43, Day 197, Day 365
GMT Neutralizing antibody titer 80 changed from baseline after vaccination
GMT Neutralizing antibody titer 80 changed from baseline after vaccination
Time frame: Day 29, Day 43, Day 197, Day 365
NT50 seroresponses changed from baseline after vaccination
Frequency of subjects with NT50 seroresponses against SARS-CoV-2 pseudovirus as defined by (1) a ≥ 4-fold increase from baseline, and (2) a ≥ 10-fold increase from baseline after vaccination
Time frame: Day 29, Day 43, Day 197, Day 365
NT80 seroresponses changed from baseline after vaccination
Frequency of subjects with NT80 seroresponses against SARS-CoV-2 pseudovirus as defined by (1) a ≥ 4-fold increase from baseline, and (2) a ≥ 10-fold increase from baseline after vaccination
Time frame: Day 29, Day 43, Day 197, Day 365
GMT Anti-S IgG after vaccination
GMT Anti-S IgG after vaccination in subjects who are anti-S IgG seronegative at baseline
Time frame: Day 29, Day 43, Day 197, Day 365
GMFR changed from baseline in anti-S IgG GMT after vaccination
GMFR changed from baseline in anti-S IgG GMT after vaccination
Time frame: Day 29, Day 43, Day 197, Day 365
Anti-S IgG Seroresponses changed from baseline after vaccination
Frequency of subjects with seroresponses in anti-S IgG titer as defined by (1) a ≥ 4-fold increase from baseline, and (2) a ≥ 10-fold increase from baseline after vaccination
Time frame: Day 29, Day 43, Day 197, Day 365
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