Covid-19 Living Data

Trial NCT04471519
Publication Ella R, Lancet Infect Dis, 2021
Dates: 07/09/2020 to 12/09/2020
Funding: Private (Bharat Biotech International Limited)
Conflict of interest: Yes

Methods
	RCT
	Location : Multicenter / India Follow-up duration (months): 3.87
	•3 mcg BBV152 + Algel-IMDG (n = 190) •6 mcg BBV152 + Algel-IMDG (n = 190)
Inclusion criteria	1. Ability to provide written informed consent 2. Participants of either gender of age between ≥12 to ≤65 years 3. Good general health as determined by the discretion of investigator (vital signs, medical history, and physical examination) 4. Expressed interest and availability to fulfill the study requirements 5. For a female participant of child-bearing potential, 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 and agrees not to participate in another clinical trial at any time during the study period 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 to remain in the study area for the entire duration of the study 10. 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. Confirmed SARS-CoV-2 at the time of screening using RT-PCR and ELISA method 3. Health care workers 4. Positive urine pregnancy test (within 24 hours of administering each dose of vaccine) 5. 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 6. Medical problems as a result of alcohol or illicit drug use during the past 12 months 7. 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 8. Receipt of any licensed vaccine within four weeks before enrolment in this study 9. Known sensitivity to any ingredient of the study vaccines, or a more severe allergic reaction and history of allergies in the past 10. Receipt of immunoglobulin or other blood products within the three months prior to vaccination in this study 11 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 12. 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) 13. Any history of hereditary angioedema or idiopathic angioedema 14. Any history of anaphylaxis in relation to vaccination 15. Any history of albumin-intolerance 16. Pregnancy, lactation, or willingness/intention to become pregnant during the study 17. History of any cancer 18. History of psychiatric severe conditions likely to affect participation in the study 19. A bleeding disorder (e.g. factor deficiency, coagulopathy or platelet disorder, or prior history of significant bleeding or bruising following IM injections or venepuncture 20. Any other serious chronic illness requiring hospital specialist supervision 21. Chronic respiratory diseases like severe acute respiratory syndrome (SARS), including mild asthma 22. Chronic cardiovascular disease, gastrointestinal disease, liver disease, renal disease, endocrine disorder, and neurological illness 23. Morbidly obese (BMI≥35 kg/m2) or underweight (BMI ≤18 kg/m2) 24. Living in the same household of any COVID-19 positive person 25. 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 26. Pregnancy 27. Anaphylactic reaction following administration of the investigational vaccine 28. Virologically confirmed cases of COVID-19
Interventions
	Intervention 2 IM doses of 6-mcg BBV152 with Algel-IMDG (alum) adjuvant, 28 days apart
	Control 2 IM doses of 3-mcg BBV152 with Algel-IMDG (alum) adjuvant, 28 days apart
Participants
	Randomized 380 participants
	Characteristics of participants Type of participants: Healthy volunteers N=380 285 males Children: 14 Pregnant women: 0 Immunocompromized patients: 0 Mean age: Age range: NR
	Description of participants Healthy adults (<65 yo) and children (≥12 yo)volunteers, SARS-CoV-2 infection-free in 9 centres in India
Primary outcome
	In the register Evaluation of Neutralizing Antibody Titers [ Time Frame: Through study completion, an average of 6 months ]
	In the report The primary outcome was SARS-CoV-2 wild-type neutralising antibody titres and seroconversion rates at 4 weeks after the second dose (day 56).
Documents available	Protocol Yes. In English Statistical plan Yes Data-sharing stated: Yes, when the trial is complete Data accessibility: upon request directed to the corresponding author, shared through a secure online platform
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, two online trial registries and the study protocol were used for data extraction and assessment of risk of bias. . This was an interim analysis of a phase 2 trial. Recruitment is completed and planned sample size has been reached, however, the study is still ongoing for longer term follow-up. There were no major differences in population, procedures or interventions between the pre-print article and registry. This trial was updated on March 31st, 2021 after publication of the study report.