Covid-19 Living Data

Trial NCT04471519; CTRI/2021/04/032942
Publication Vadrevu KM, Sci Rep, 2022
Dates: 2021-04-10 to 2021-04-14
Funding: Private (Bharat Biotech International Limited)
Conflict of interest: Yes

Methods
	RCT
	Location : Multicenter / India Follow-up duration (months): 1
	BBV152 (n = 91) Placebo (n = 93)
Inclusion criteria	Ability to provide written informed consent (Audio video consent for vulnerable subjects) either gender of age between ≥12 to ≤ 65 years 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) Expressed interest and availability to fulfill the study requirements 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 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 Male subjects agree to refrain from sperm donation from the time of first vaccination until 3 months after last vaccination Participants must refrain from blood or plasma donation from the time of first vaccination until 3 months after last vaccination Agrees to remain in the study area for the entire duration of the study Willing to allow storage and future use of biological samples for future research.
Exclusion criteria	History of any other COVID-19 investigational vaccination Confirmed SARS-CoV-2 at the time of screening using RT-PCR and ELISA method Health care workers Positive urine pregnancy test (within 24 hours of administering each dose of vaccine) 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 Medical problems as a result of alcohol or illicit drug use during the past 12 months Receipt of an experimental agent (vaccine, drug, device, etc.) within 60 days before enrolment or expects to receive an investigational agent during the study period Receipt of any licensed vaccine within four weeks before enrolment in this study Known sensitivity to any ingredient of the study vaccines, or a more severe allergic reaction and history of allergies in the past Receipt of immunoglobulin or other blood products within the three months prior to vaccination in this study 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 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) Any history of hereditary angioedema or idiopathic angioedema Any history of anaphylaxis in relation to vaccination Any history of albumin-intolerance Pregnancy, lactation, or willingness/intention to become pregnant during the study History of any cancer History of psychiatric severe conditions likely to affect participation in the study A bleeding disorder (e.g. factor deficiency, coagulopathy or platelet disorder, or prior history of significant bleeding or bruising following IM injections or venepuncture Any other serious chronic illness requiring hospital specialist supervision Chronic respiratory diseases like severe acute respiratory syndrome (SARS), including mild asthma Chronic cardiovascular disease, gastrointestinal disease, liver disease, renal disease, endocrine disorder, and neurological illness Morbidly obese (BMI≥35 kg/m2) or underweight (BMI ≤18 kg/m2) Living in the same household of any COVID-19 positive person 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.
Interventions
	Intervention 1 6mcg IM dose of BBV152, 6 months after 2-dose primary schedule
	Control 1 IM dose of adjuvant, 6 months after 2-dose primary schedule
Participants
	Randomized 184 participants
	Characteristics of participants Type of participants: Adolescents and adults N=184 140 males Children: 4 Pregnant women: 0 Immunocompromized patients: 0 Mean age: Age range: NR
	Description of participants Adolescents and adults aged 12-64 years with no history of confirmed COVID-19, who had received a 2-dose schedule of the same vaccine 6 months previously at 9 centers in India.
Primary outcome
	In the register Evaluation of Neutralizing Antibody Titers [ Time Frame: Through study completion, an average of 6 months ] Pre- and Post-vaccination immune response
	In the report Neutralising antibody titres against wild-type virus evaluated by two neutralisation assays; a plaque-reduction neutralisation test (PRNT) and a microneutralisation assay (MNT)
Documents available	Protocol NR Statistical plan * Data-sharing stated: Yes, When the trial is complete Data accessibility: Direct request to the corresponding author: Raches Ella - rachesella@gmail.com
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 article, the pre-print article and the trial registry were used in data extraction and assessment of risk of bias. The registry referred to the original Phase 1 and 2 trials; the current study was an extension of the Phase 2 trial to evaluate a booster vaccination. Neither protocol nor statistical analysis plan was available. The primary outcome in the article reflects that in the registry. This trial was updated on September 20th, 2022 after publication of the study report.