NDV-HXP-S Vaccine Clinical Trial (COVIVAC)

Study Overview
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Brief Summary
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This prospective, single-center, randomized, placebo-controlled (phase 1) and active-controlled (phase 2), observer-blind Phase 1/2 study includes two separate parts. After completing the phase 1 interim analysis, 2 doses (3mcg and 6mcg) were selected for phase 2. In Part 2 of this combined Phase 1/2 study, 374 adults aged 18-75 years will be randomized (1:1:1) to AZD1222, or COVIVAC 3 µg being evaluated in Phase 1 or the intermediate dose of COVIVAC 6 µg being selected after consideration of phase 1 results.

Detailed Description
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In Part 2 of this combined Phase 1/2 study, 374 adults aged 18-75 years will be randomized (1:1:1) to placebo, or COVIVAC 3 µg being evaluated in Phase 1 or the intermediate dose of COVIVAC 6 µg being selected after consideration of phase 1 results. At least one-third of the subjects in Phase 2 will be aged ≥60 years to ensure that adequate safety and immune data will be available from older and elderly adults to inform the selection of the COVIVAC formulation to advance to Phase 3 studies. The Phase 2 cohort will follow the same visit schedule, and undergo the same procedures and assessments, as in Phase 1. In addition, as exploratory objectives, the anti-NDV HN IgG response will be assessed at V1, V3, V5, and V7 in all subjects, and 36 subjects (equally distributed between the two age strata) will be randomly selected in a 1:1:1 ratio to provide additional blood at V1, V5 and V7 to be used to isolate peripheral blood mononuclear cells (PBMCs) for assessment of T-cell-mediated immunity (CMI). An interim analysis of Phase 2 data will be conducted after the last subject of the Phase 2 cohort completes V6 (D57) as the basis for selecting the optimal formulation of COVIVAC to advance to Phase 3 studies. As was the case for the Phase 1 interim analysis at the same timepoint, the data generated will include unblinded post-dose 1 and dose 2 safety results for review by the DSMB, and immunogenicity results aggregated by treatment group for review by the Sponsor. The DSMB will consider all accumulated safety data from both phases of the study prior to making any recommendation to the Sponsor that it not advance a formulation based on safety concerns. The Sponsor will ultimately select the formulation to advance to Phase 3 that, in addition to having been judged by the DSMB to have an adequate safety and tolerability profile, is optimal based on relative functional immunogenicity and other programmatic considerations such as those noted above.

Official Title
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A Phase 1/2 Randomized, Active- Controlled, Observer-blind Trial to Assess the Safety and Immunogenicity of COVIVAC Vaccine Produced by IVAC in Adults ≥ 18 and ≥ 60 Years Old in Vietnam

Conditions
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COVID-19

Intervention / Treatment
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* Biological: COVIVAC vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult ≥ 18 years old inclusive at the time of randomization. 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. 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. If a woman is of childbearing potential age, must not be breastfeeding or be pregnant (based on a negative urine pregnancy test at screening and during the 24 hours prior to receipt of the first dose of IP), must plan to avoid pregnancy for at least 28 days after the last dose of IP, and be willing to use an adequate method of contraception consistently and have a repeated pregnancy test prior to the second (last) dose of IP. Exclusion Criteria: 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 within 3 months after enrolment. Note: receipt of any COVID-19 vaccine that is licensed or granted Emergency Use Authorization in Vietnam 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 (≥ grade 2) Acute illness (moderate or severe) and/or fever (body temperature measured orally ≥38°C) Any abnormal vital sign deemed clinically relevant by the PI Abnormality in screening laboratory test deemed exclusionary by the PI in consultation with the Sponsor A positive serologic test for hepatitis B (HBsAg) or hepatitis C (HCV Ab) (phase 1 only) History of confirmed HIV History of laboratory-confirmed COVID-19 History of malignancy, excluding non-melanoma skin and cervical carcinoma in situ Any confirmed or suspected immunosuppressive or immunodeficient state Administration of immunoglobulin or any blood product within 90 days prior to first study injection or planned administration during the study period. Administration of any long-acting immune-modifying drugs (e.g., infliximab or rituximab) or the chronic administration (defined as more than 14 days) of immunosuppressants within six months prior to first study injection, or planned administration during the study period (includes systemic corticosteroids at doses equivalent to ≥ 0.5 mg/kg/day of prednisone; the use of topical steroids including inhaled and intranasal steroids is permitted). History of known disturbance of coagulation or blood disorder that could cause anemia or excess bleeding. (e.g, thalassemia, coagulation factor deficiencies). Recent history (within the past year) or signs of alcohol or substance abuse. Any medical, psychiatric or behavior condition that in the opinion of the PI may interfere with the study objectives, pose a risk to the subject, or prevent the subject from completing the study follow-up. Employee of any person employed by the Sponsor, the contract research organization (CRO), the PI, study site personnel, or site.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: COVIVAC 3 mcg<br>3 mcg IVAC COVIVAC vaccine for intramuscular injection administered as two doses (0.5mL each) 28 days apart. | Biological: COVIVAC vaccine<br>* For prevention Covid-19<br>|
| Experimental: COVIVAC 6 mcg<br>6 mcg IVAC COVIVAC vaccine for intramuscular injection administered as two doses (0.5mL each) 28 days apart. | Biological: COVIVAC vaccine<br>* For prevention Covid-19<br>|
| Active Comparator: AZD1222<br>AZD1222 (AstraZeneca) vaccine for intramuscular injection administered as two doses (0.5mL each) 28 days apart. | Biological: COVIVAC vaccine<br>* For prevention Covid-19<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Solicited AE | Number and severity of solicited local and systemic AEs during the first 7 days after each vaccination | 7 days after each vaccination | 
| Unsolicited AE | Number, severity and relatedness of all unsolicited AEs during the first 28 days after each vaccination | 28 days after each vaccination | 
| SAE | Number, severity and relatedness of SAEs throughout the entire study period | Throughout the entire study period | 
| AE of Special interest (AESI) | Number, severity and relatedness of AESI throughout the entire study period, including AESI relevant to COVID-19, and potential immune-mediated medical conditions (PIMMC) | Throughout the entire study period | 
| NT50 GMT | NT50 GMT against SARS-CoV-2 pseudovirus in subjects who are anti-S IgG seronegative at baseline | 14 days and 6 months after second vaccination | 
| GMFR in NT50 | GMFR (from baseline) in NT50 against SARS-CoV-2 pseudovirus | 14 days and 6 months after second vaccination | 
| Seroresponse in NT50 | Percentage 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 | 14 days and 6 months after second vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| IgG GMT | Anti-S IgG GMT in subjects who are anti-S IgG seronegative at baseline | 14 days and 6 months after the second vaccination | 
| GMFR in anti-S IgG GMT | GMFR (from baseline) in anti-S IgG GMT | 14 days and 6 months after the second vaccination | 
| Seroresponse in anti-S IgG | Percentage 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 | 14 days and 6 months after the second vaccination |