Covid-19 Living Data

Trial NCT04764422
Publication Pitisuttithum P, medRxiv, 2021
Dates: 2021-03-20 to 2021-04-23
Funding: Public/non profit (National Vaccine Institute (Thailand), National Research Council (Thailand), Bill & Melinda Gates Foundation, National Institutes of Health (USA))
Conflict of interest: Yes

Methods
	RCT
	Location : Single center / Thailand Follow-up duration (months): 1.9
	1 mcg NDV-HXP-S (n=35) 1 mcg NDV-HXP-S + CpG1018 adjuvant (n=35) 3 mcg NDV-HXP-S (n=35) 3 mcg NDV-HXP-S + CpG1018 adjuvant (n=35) 10 mcg NDV-HXP-S (n=35) Saline placebo (n=35)
Inclusion criteria	Healthy adults 18–59 years of age body mass index 17 to 40 kg/m2 negative6 hepatitis B surface antigen and SARS-CoV-2, HIV, and hepatitis C antibody tests negative urinary pregnancy test (for women having reproductive capacity prior to administration of each study vaccine dose)
Exclusion criteria	Positive serologic test for SARS-CoV-2 IgG test 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 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 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) History of laboratory-confirmed COVID-19 (RT-PCR positive to SAR-CoV-2) 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.
Interventions
	Intervention 2 IM doses of 1 mcg, 28 days apart 2 IM doses of 1 mcg + adjuvant, 28 days apart 2 IM doses of 3 mcg, 28 days apart 2 IM doses of 3 mcg + adjuvant, 28 days apart 2 IM doses of 10 mcg, 28 days apart
	Control 2 IM doses, 28 days apart
Participants
	Randomized 210 participants
	Characteristics of participants Type of participants: Healthy adults N=210 82 males Children: 0 Pregnant women: 0 Immunocompromized patients: 0 Mean age: Age range: NR
	Description of participants Healthy adults without immunosuppression negative for SARS-CoV-2 antibodies at a single center in Thailand
Primary outcome
	In the register 1-4. Frequency of solicited reportable local adverse event / systemic adverse event after first vaccination / after second vaccination [ Time Frame: Day 1 up to Day 7 ]; 5-18. Measurement of hemoglobin / white blood cells / platelet count / creatinine / AST / ALT / total bilirubin changed from baseline at 7 days after first vaccination / after second vaccination; 19. Frequency of all unsolicited AEs [ Time Frame: Day 56 ]; 20. Frequency of SAEs [ Time Frame: Day 365 ]; 21. Frequency of medically-attended adverse event (MAAEs) [ Time Frame: Day 365 ]; 22. Frequency of AESI [ Time Frame: Day 365 ]
	In the report Frequency and intensity of solicited injection site and systemic AEs during 7 days after vaccination; frequency, intensity, and relatedness of clinically significant haematological and biochemical measurements at 7 days after each vaccination; frequency, intensity, and relatedness of unsolicited AEs during 28 days after each vaccination; and occurrence of medically-attended AEs, serious AEs, and AEs of special interest during the interim analysis period of 57 days after-first vaccination
Documents available	Protocol NR Statistical plan * Data-sharing stated: Yes, 2 years after vaccine marketing Data accessibility: Corresponding author: Bruce L Innis: binnis@path.org
Risk of bias Overall The overall risk of bias reported in the table corresponds to the highest risk of bias for the outcomes assessed for the systematic review	Some concerns
General comment	In addition to the pre-print article, the study registry was used in data extraction and risk of bias assessment. Neither protocol nor statistical analysis plan was available. The pre-print reported on phase 1 of a phase 1/2 trial with ongoing follow-up. The primary outcomes in the article reflect the short term outcomes in the registry.