Covid-19 Living Data

Trial NCT04471519
Publication Ella R, Lancet Infect Dis, 2021
Dates: 13/07/2020 to 30/07/2020
Funding: Private (Bharat Biotech International Limited)
Conflict of interest: Yes

Methods
	RCT
	Location : Multicenter / India Follow-up duration (months): 6.38
	•3 mcg BBV152 + Algel-IMDG (n = 100) •6 mcg BBV152 + Algel-IMDG (n = 100) •6 mcg BBV152 + Algel (n = 100) •Placebo (n = 75)
Inclusion criteria	1. Ability to provide written informed consent 2. Participants of either gender of age between ≥18 to ≤55 years 3. Good general health as determined by the discretion of investigator (vital signs (heart rate ≥60 to ≤100 bpm blood pressure systolic ≥90 mm Hg and <140 mm Hg diastolic ≥ 60 mm Hg and <90 mm Hg oral temperature <100.4ºF), medical history, and physical examination) 4. Expressed interest and availability to fulfill the study requirements 5. For a female participant of child-bearing potential, planning to avoid becoming pregnant (use of an effective method of contraception or abstinence) from the time of study enrolment until at least four weeks after the last vaccination 6. Male subjects of reproductive potential: Use of condoms to ensure effective contraception with the female partner from first vaccination until 3 months after last vaccination 7. Male subjects agree to refrain from sperm donation from the time of first vaccination until 3 months after last vaccination 8. Participants must refrain from blood or plasma donation from the time of first vaccination until 3 months after last vaccination 9. Agrees not to participate in another clinical trial at any time during the study period 10. Agrees to remain in the study area for the entire duration of the study 11. Willing to allow storage and future use of biological samples for future research.
Exclusion criteria	1. History of any other COVID-19 investigational vaccination 2. Unacceptable laboratory abnormality from screening (prior to first vaccination) or safety testing, as listed below [Abnormal Complete Blood Count (CBC), Random blood sugar level, Renal function test (serum urea and Creatinine), liver function tests, urine analysis report, Positive serology for hepatitis C or HIV antibody or hepatitis B surface antigen]. (Subjects will be informed if their results are positive for hepatitis C, HIV 1 & 2 antibody or hepatitis B surface antigen (HBsAg) and will be referred to a primary care provider for follow up of these abnormal laboratory tests.) 3. Confirmed SARS-CoV-2 at the time of screening using RT-PCR and ELISA method 4. Health care workers 5. For women, a positive serum pregnancy test (during screening within 45 days of enrolment) or positive urine pregnancy test (within 24 hours of administering each dose of vaccine) 6. Temperature >38.0°C (100.4°F) or symptoms of an acute self-limited illness such as an upper respiratory infection or gastroenteritis within three days prior to each dose of vaccine 7. Medical problems as a result of alcohol or illicit drug use during the past 12 months 8. Receipt of an experimental agent (vaccine, drug, device, etc.) within 60 days before enrollment or expects to receive an investigational agent during the study period 9. Receipt of any licensed vaccine within four weeks before enrolment in this study 10. Known sensitivity to any ingredient of the study vaccines, or a more severe allergic reaction and history of allergies in the past 11. Receipt of immunoglobulin or other blood products within the three months prior to vaccination in this study 12. Immunosuppression as a result of an underlying illness or treatment with immunosuppressive or cytotoxic drugs, or use of anticancer chemotherapy or radiation therapy within the preceding 36 months 13. Long-term use (> 2 weeks) of oral or parenteral steroids (glucocorticoids) or high-dose inhaled steroids (>800 mcg/day of beclomethasone dipropionate or equivalent) within the preceding six months (nasal and topical steroids are allowed) 14. Any history of hereditary angioedema or idiopathic angioedema 15. Any history of anaphylaxis in relation to vaccination 16. Any history of albumin-intolerance 17. Pregnancy, lactation, or willingness/intention to become pregnant during the study 18. History of any cancer 19. History of psychiatric severe conditions likely to affect participation in the study 20. A bleeding disorder (e.g. factor deficiency, coagulopathy or platelet disorder, or prior history of significant bleeding or bruising following IM injections or venipuncture 21. Any other serious chronic illness requiring hospital specialist supervision 22. Chronic respiratory diseases like severe acute respiratory syndrome (SARS), including mild asthma 23. Chronic cardiovascular disease, gastrointestinal disease, liver disease, renal disease, endocrine disorder, and neurological illness 24. Morbidly obese (BMI≥35 kg/m2) or underweight (BMI ≤18 kg/m2) 25. Living in the same household of any COVID-19 positive person 26. Any other condition that in the opinion of the investigator would jeopardize the safety or rights of a volunteer participating in the trial or would render the subject unable to comply with the protocol Re-Vaccination Exclusion Criteria 27. Pregnancy 28. Anaphylactic reaction following administration of the investigational vaccine 29. Virologically confirmed cases of COVID-19
Interventions
	Intervention 2 IM doses of 3-mcg BBV152 with Algel-IMDG (alum) adjuvant, 14 days apart 2 IM doses of 6-mcg BBV152 with Algel-IMDG (alum) adjuvant, 14 days apart 2 IM doses of 6-mcg BBV152 with Algel (alum) adjuvant, 14 days apart
	Control 2 IM doses of Algel (alum) adjuvant, 14 days apart
Participants
	Randomized 375 participants
	Characteristics of participants Type of participants: Healthy volunteers N=375 297 males Children: 0 Pregnant women: 0 Immunocompromized patients: 0 Mean age: NR Age range: 18-55
	Description of participants Healthy SARS-CoV-2 serology/PCR negative adults in 11 centres in India
Primary outcome
	In the register Occurrence of adverse events and Serious Adverse events [ Time Frame: Through study completion, an average of 6 months ]
	In the report Primary outcomes were solicited local and systemic reactogenicity events at 2 h and 7 days after vaccination and throughout the full study duration, including serious adverse events.
Documents available	Protocol NR Statistical plan * Data-sharing stated: Yes, When the trial is complete, Data accessibility: The corresponding authors
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 published report, the two online trial registries and the spplementary appendix were used for data extraction and assessment of risk of bias. Recruitment is completed and planned sample size has been reached. There were no major differences in population, procedures or interventions between the pre-print article and registry. This trial was updated on February 18th, 2021 after study report publication.