A Phase 1/2 Randomized, Placebo-controlled, Observer-blind Trial to Assess the Safety and Immunogenicity of NDV-HXP-S Vaccine in Thailand
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- Covid-19
- Sponsor
- Mahidol University
- Enrollment
- 455
- Locations
- 1
- Primary Endpoint
- Measurement of white blood cells changed from baseline at 7 days after first and second vaccination
- Status
- Completed
- Last Updated
- 3 years ago
Overview
Brief Summary
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.
Detailed Description
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.
Investigators
Punnee Pitisuttithum
Professor
Mahidol University
Eligibility Criteria
Inclusion Criteria
- •Phase 1 Only:
- •Adult 18 through 59 years of age, inclusive, at screening
- •Healthy, as defined by absence of clinically significant medical condition, either acute or chronic, as determined by medical history, physical examination, screening laboratory test results, and clinical assessment of the investigator.
- •Phase 2 Only:
- •Adult 18 through 75 years of age, inclusive, at screening.
- •Having no clinically significant acute medical condition, and no chronic medical condition that has not been controlled within 90 days of randomization, as determined by medical history, physical examination, screening laboratory test results, and clinical assessment of the investigator.
- •Both Phase 1 and Phase 2:
- •Has provided written informed consent prior to performance of any study-specific procedure.
- •Has a body mass index (BMI) of 17 to 40 kg/m2, inclusive, at screening.
- •Resides in study site area and is able and willing to adhere to all protocol visits and procedures.
Exclusion Criteria
- •Phase 1 Only:
- •A positive serologic test for SARS-CoV-2 IgG test.
- •Both Phase 1 and Phase 2:
- •Use of any investigational medicinal product within 90 days prior to randomization or planned use of such a product during the period of study participation.
- •History of administration of any non-study vaccine within 28 days prior to administration of study vaccine or planned vaccination during the course of study participation Note: receipt of any COVID-19 vaccine that is licensed or granted Emergency Use Authorization in Thailand during the course of study participation is not exclusionary if administered after Visit 5
- •Previous receipt of investigational vaccine for SARS or MERS, or any investigational or licensed vaccine that may have an impact on interpretation of the trial results
- •History of hypersensitivity reaction to any prior vaccination or known hypersensitivity to any component of the study vaccine
- •History of egg or chicken allergy
- •History of angioedema
- •History of anaphylaxis
Outcomes
Primary Outcomes
Measurement of white blood cells changed from baseline at 7 days after first and second vaccination
Time Frame: Day 8, Day 36
Measurement of white blood cells (10\^3 cells/ul) changed from baseline at 7 days after first and second vaccination
Frequency of solicited reportable local adverse event after first vaccination
Time Frame: Day 1 up to Day 7 after first vaccination
Frequency of solicited reportable local adverse events (pain or tenderness, erythema, swelling or induration) of first vaccination
Frequency of solicited reportable local adverse event after second vaccination
Time Frame: Day 1 up to Day 7 after second vaccination
Frequency of solicited reportable local adverse events (pain or tenderness, erythema, swelling or induration) of second vaccination
Frequency of solicited reportable systemic adverse event after first vaccination
Time Frame: Day 1 up to Day 7 after first vaccination
Frequency of solicited reportable systemic adverse events (fever, headache,fatigue or malaise, myalgia, arthralgia,nausea or vomitting) of first vaccination
Frequency of solicited reportable systemic adverse event after second vaccination
Time Frame: Day 1 up to Day 7 after second vaccination
Frequency of solicited reportable systemic adverse events (fever, headache,fatigue or malaise, myalgia, arthralgia,nausea or vomitting) of second vaccination
Measurement of hemoglobin changed from baseline at 7 days after first and second vaccination
Time Frame: Day 8, Day 36
Measurement of hemoglobin (g/dl) changed from baseline at 7 days after first and second vaccination
Measurement of platelet count changed from baseline at 7 days after first and second vaccination
Time Frame: Day 8, Day 36
Measurement of platelet count (10\^3 cells/ul) changed from baseline at 7 days after first and second vaccination
Measurement of creatinine changed from baseline at 7 days after first and second vaccination
Time Frame: Day 8, Day 36
Measurement of creatinine (mg/dl) changed from baseline at 7 days after first and second vaccination
Measurement of total bilirubin changed from baseline at 7 days after first and second vaccination
Time Frame: Day 8, Day 36
Measurement of total bilirubin (mg/dl) change from baseline at 7 days after first and second vaccination
Measurement of AST changed from baseline at 7 days after first and second vaccination
Time Frame: Day 8, Day 36
Measurement of AST (U/L) changed from baseline at 7 days after first and second vaccination
Measurement of ALT change from baseline at 7 days after first and second vaccination
Time Frame: Day 8, Day 36
Measurement of ALT (U/L) change from baseline at 7 days after first and second vaccination
Frequency of all unsolicited AEs
Time Frame: Day 1 up to Day 56
Frequency of all unsolicited AEs
Frequency of SAEs
Time Frame: Day 1 up to Day 365
Frequency of SAEs throughout the entire study period
Frequency of medically-attended adverse event (MAAEs)
Time Frame: Day 1 up to Day 365
Frequency of medically-attended adverse event (MAAEs) throughout the entire study period
Frequency of AESI
Time Frame: Day 1 up to Day 365
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
Secondary Outcomes
- GMT Neutralizing antibody titer 50 changed from baseline after vaccination(Day 29, Day 43, Day 197, Day 365)
- GMT Neutralizing antibody titer 80 changed from baseline after vaccination(Day 29, Day 43, Day 197, Day 365)
- NT50 seroresponses changed from baseline after vaccination(Day 29, Day 43, Day 197, Day 365)
- NT80 seroresponses changed from baseline after vaccination(Day 29, Day 43, Day 197, Day 365)
- GMT Anti-S IgG after vaccination(Day 29, Day 43, Day 197, Day 365)
- GMFR changed from baseline in anti-S IgG GMT after vaccination(Day 29, Day 43, Day 197, Day 365)
- Anti-S IgG Seroresponses changed from baseline after vaccination(Day 29, Day 43, Day 197, Day 365)