Assess the Safety and Immunogenicity of NDV-HXP-S Vaccine in Thailand

A Phase 1/2 Randomized, Placebo-controlled, Observer-blind Trial to Assess the Safety and Immunogenicity of NDV-HXP-S Vaccine in Thailand

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.

Study Overview

• Status: Completed
• Conditions: Pneumonia, Viral; Covid-19; SARS Pneumonia; Covid-19 Vaccine
• Intervention / Treatment: Biological: Normal Saline; Biological: NDV-HXP-S vaccine

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.

• Study Type: Interventional
• Enrollment (Actual): 455
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Thailand
  • Bangkok, Thailand, 10400
    • Vaccine Trial Centre, Faculty of Tropical Medicine, Mahidol University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Phase 1 Only:

1. Adult 18 through 59 years of age, inclusive, at screening
2. 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:

1. Adult 18 through 75 years of age, inclusive, at screening.
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.

Both Phase 1 and Phase 2:

1. Has provided written informed consent prior to performance of any study-specific procedure.
2. Has a body mass index (BMI) of 17 to 40 kg/m2, inclusive, at screening.
3. Resides in study site area and is able and willing to adhere to all protocol visits and procedures.
4. If a woman is of childbearing potential, must not be breastfeeding or be pregnant (based on a negative serum pregnancy test at screening and a negative urine pregnancy test 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:

Phase 1 Only:

1. A positive serologic test for SARS-CoV-2 IgG test.

Both Phase 1 and Phase 2:

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 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
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
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.
11. A positive serologic test for SARS-CoV-2 IgM test, human immunodeficiency virus (HIV 1/2 Ab), hepatitis B (HBsAg) or hepatitis C (HCV Ab)
12. History of laboratory-confirmed COVID-19 (RT-PCR positive to SAR-CoV-2)
13. History of malignancy, excluding non-melanoma skin and cervical carcinoma in situ
14. Any confirmed or suspected immunosuppressive or immunodeficient state
15. Administration of immunoglobulin or any blood product within 90 days prior to first study injection or planned administration during the study period.
16. 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).
17. History of known disturbance of coagulation or blood disorder that could cause anemia or excess bleeding. (e.g, thalassemia, coagulation factor deficiencies).
18. Recent history (within the past year) or signs of alcohol or substance abuse.
19. 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.
20. Employee of any person employed by the Sponsor, the contract research organization (CRO), the PI, study site personnel, or site.

Note: specific exclusion criteria (e.g., ≥Grade 2 acute illness, or abnormal vital sign deemed clinically relevant by the PI) will be reassessed at both vaccination visits. Any subject who cannot be vaccinated due to an acute abnormality assessed at a vaccination visit (Visit 1 or Visit 3) may return once the acute issue has resolved, if deemed appropriate by the PI. A minimum of 48 hours must have passed after a documented fever before a subject can be vaccinated. This safety requirement will not be deemed a protocol deviation should the visit fall outside the vaccination window; however, it will be encouraged to maintain the vaccination window whenever possible in these situations. Clinical laboratory test results and vital signs used to determine subject eligibility will be those obtained at screening. These tests may be repeated once if deemed appropriate by the investigator and determined to be due to a transient condition that has resolved. In addition, a test may also be repeated for test results determined to be spurious by the investigator (e.g., following improper specimen collection). The last measurement will be taken as the baseline for purposes of analysis.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Double

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; 0.9% Normal Saline for injection	Biological: Normal Saline; 0.9% normal saline for injection
Active Comparator: NDV-HXP-S 1 µg; 35 subjects age 18-59 will receive NDV-HXP-S 1 µg study vacine administered 0.5 mL IM	Biological: NDV-HXP-S vaccine; Vaccine NDV-HXP-S, manufactured by GPO with or without adjuvant CpG1018.
Active Comparator: NDV-HXP-S 3 µg; 35 subjects age 18-59 will receive NDV-HXP-S 3 µg study vacine administered 0.5 mL IM	Biological: NDV-HXP-S vaccine; Vaccine NDV-HXP-S, manufactured by GPO with or without adjuvant CpG1018.
Active Comparator: NDV-HXP-S 10 µg; 35 subjects age 18-59 will receive NDV-HXP-S 10 µg study vacine administered 0.5 mL IM	Biological: NDV-HXP-S vaccine; Vaccine NDV-HXP-S, manufactured by GPO with or without adjuvant CpG1018.
Active Comparator: NDV-HXP-S 1 µg + CpG1018 1.5 mg; 35 subjects age 18-59 will receive NDV-HXP-S 1 µg + CpG1018 1.5 mg study vacine administered 0.5 mL IM	Biological: NDV-HXP-S vaccine; Vaccine NDV-HXP-S, manufactured by GPO with or without adjuvant CpG1018.
Active Comparator: NDV-HXP-S 3 µg + CpG1018 1.5 mg; 35 subjects age 18-59 will receive NDV-HXP-S 3 µg + CpG1018 1.5 mg study vacine administered 0.5 mL IM	Biological: NDV-HXP-S vaccine; Vaccine NDV-HXP-S, manufactured by GPO with or without adjuvant CpG1018.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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	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	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	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	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	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	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	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	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	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	Day 8, Day 36
Frequency of all unsolicited AEs	Frequency of all unsolicited AEs	Day 1 up to Day 56
Frequency of SAEs	Frequency of SAEs throughout the entire study period	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	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	Day 1 up to Day 365

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
GMT Neutralizing antibody titer 50 changed from baseline after vaccination	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	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	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	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	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	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	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	Day 29, Day 43, Day 197, Day 365

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
S protein-specific T cells response changed from baseline after vaccination	Frequency of S protein-specific T cells relative to baseline after vaccination	Day 43, Day 197
Anti-NDV HN GMT changed from baseline after vaccination	Anti-NDV HN GMT changed from baseline after vaccination	Day 29, Day 43, Day 197, Day 365
Anti-NDV HN IgG GMT changed from baseline after vaccination	Anti-NDV HN IgG GMT changed from baseline after vaccination	Day 29, Day 43, Day 197, Day 365

Collaborators and Investigators

• Sponsor: Mahidol University
• Collaborators: The Government Pharmaceutical Organization
• Investigators: Principal Investigator: Punnee Pitisutthithum, Vaccine Trial Centre, Faculty of Tropical Medicine, Mahidol University

Publications and helpful links

General Publications

• Pitisuttithum P, Luvira V, Lawpoolsri S, Muangnoicharoen S, Kamolratanakul S, Sivakorn C, Narakorn P, Surichan S, Prangpratanporn S, Puksuriwong S, Lamola S, Mercer LD, Raghunandan R, Sun W, Liu Y, Carreño JM, Scharf R, Phumratanaprapin W, Amanat F, Gagnon L, Hsieh CL, Kaweepornpoj R, Khan S, Lal M, McCroskery S, McLellan J, Mena I, Meseck M, Phonrat B, Sabmee Y, Singchareon R, Slamanig S, Suthepakul N, Tcheou J, Thantamnu N, Theerasurakarn S, Tran S, Vilasmongkolchai T, White JA, Bhardwaj N, Garcia-Sastre A, Palese P, Krammer F, Poopipatpol K, Wirachwong P, Hjorth R, Innis BL. Safety and immunogenicity of an inactivated recombinant Newcastle disease virus vaccine expressing SARS-CoV-2 spike: Interim results of a randomised, placebo-controlled, phase 1 trial. EClinicalMedicine. 2022 Mar 8;45:101323. doi: 10.1016/j.eclinm.2022.101323. eCollection 2022 Mar.
• Pitisuttithum P, Luvira V, Lawpoolsri S, Muangnoicharoen S, Kamolratanakul S, Sivakorn C, Narakorn P, Surichan S, Prangpratanporn S, Puksuriwong S, Lamola S, Mercer LD, Raghunandan R, Sun W, Liu Y, Carreno JM, Scharf R, Phumratanaprapin W, Amanat F, Gagnon L, Hsieh CL, Kaweepornpoj R, Khan S, Lal M, McCroskery S, McLellan J, Mena I, Meseck M, Phonrat B, Sabmee Y, Singchareon R, Slamanig S, Suthepakul N, Tcheou J, Thantamnu N, Theerasurakarn S, Tran S, Vilasmongkolchai T, White JA, Garcia-Sastre A, Palese P, Krammer F, Poopipatpol K, Wirachwong P, Hjorth R, Innis BL. Safety and Immunogenicity of an Inactivated Recombinant Newcastle Disease Virus Vaccine Expressing SARS-CoV-2 Spike: Interim Results of a Randomised, Placebo-Controlled, Phase 1/2 Trial. medRxiv. 2021 Sep 22:2021.09.17.21263758. doi: 10.1101/2021.09.17.21263758. Preprint.

Study record dates

Study Major Dates

• Study Start (Actual): March 20, 2021
• Primary Completion (Actual): September 12, 2022
• Study Completion (Actual): September 12, 2022

Study Registration Dates

• First Submitted: February 8, 2021
• First Submitted That Met QC Criteria: February 17, 2021
• First Posted (Actual): February 21, 2021

Study Record Updates

• Last Update Posted (Actual): November 15, 2022
• Last Update Submitted That Met QC Criteria: November 13, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: SARS-CoV-2; COVID-19; COVID-19 VACCINE; ADULT; THAILAND; GPO; The Government Pharmaceutical Organization; SAFETY; TOLERABILITY; IMMUNOGENICITY; NDV-HXP-S Vaccine; CpG1018
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; COVID-19; Pneumonia; Pneumonia, Viral
• Other Study ID Numbers: GPO NDV-HXP-S

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: data or left over specimen will be shared for future study ONLY subject who consent allow using their data/specimens. Sharing will be done without personnel identification
• IPD Sharing Time Frame: 2 years after vaccine marketing
• IPD Sharing Access Criteria: as document attach when completed study in NCT clinicaltrials.gov
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP)

Drug and device information, study documents

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