NDV-HXP-S Vaccine Clinical Trial (COVIVAC)

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

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.

Study Overview

• Status: Completed
• Conditions: COVID-19
• Intervention / Treatment: Biological: COVIVAC vaccine

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 374
• Phase: Phase 2

Contacts and Locations

Study Locations

• Vietnam
  • Thai Binh
    • Thái Bình, Thai Binh, Vietnam, 414900
      • District Health Center of Vu Thu District

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Adult ≥ 18 years old inclusive at the time of randomization.
2. 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.
3. Has provided written informed consent prior to performance of any study-specific procedure.
4. Has a body mass index (BMI) of 17 to 40 kg/m2, inclusive, at screening.
5. Resides in study site area and is able and willing to adhere to all protocol visits and procedures.
6. 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:

1. 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.

2. 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.

3. 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
4. History of hypersensitivity reaction to any prior vaccination or known hypersensitivity to any component of the study vaccine
5. History of egg or chicken allergy
6. History of angioedema
7. History of anaphylaxis (≥ grade 2)
8. Acute illness (moderate or severe) and/or fever (body temperature measured orally ≥38°C)
9. Any abnormal vital sign deemed clinically relevant by the PI
10. Abnormality in screening laboratory test deemed exclusionary by the PI in consultation with the Sponsor
11. A positive serologic test for hepatitis B (HBsAg) or hepatitis C (HCV Ab) (phase 1 only)
12. History of confirmed HIV
13. History of laboratory-confirmed COVID-19
14. History of malignancy, excluding non-melanoma skin and cervical carcinoma in situ
15. Any confirmed or suspected immunosuppressive or immunodeficient state
16. Administration of immunoglobulin or any blood product within 90 days prior to first study injection or planned administration during the study period.
17. 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).
18. History of known disturbance of coagulation or blood disorder that could cause anemia or excess bleeding. (e.g, thalassemia, coagulation factor deficiencies).
19. Recent history (within the past year) or signs of alcohol or substance abuse.
20. 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.
21. Employee of any person employed by the Sponsor, the contract research organization (CRO), the PI, study site personnel, or site.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cell mediated immunogenicity	Magnitude, functionality, and Th polarization of S protein-specific T cells relative to baseline	14 days and 6 months after the second vaccination

Collaborators and Investigators

• Sponsor: Institute of Vaccines and Medical Biologicals, Vietnam
• Collaborators: National Institute of Hygiene and Epidemiology (NIHE), Vietnam; Center for Disease Control of Thai Binh Province, Vietnam

Study record dates

Study Major Dates

• Study Start (Actual): August 11, 2021
• Primary Completion (Actual): October 18, 2021
• Study Completion (Actual): March 11, 2022

Study Registration Dates

• First Submitted: July 8, 2023
• First Submitted That Met QC Criteria: July 8, 2023
• First Posted (Actual): July 11, 2023

Study Record Updates

• Last Update Posted (Actual): July 14, 2023
• Last Update Submitted That Met QC Criteria: July 12, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19
• Other Study ID Numbers: COVIVAC-0102 (Phase 2)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No