Trial NCT04523571 ; ChiCTR
Publication Zhu F, ResearchSquare, 2021
Dates: 18/07/2021 to 14/08/2021
Funding: Private (BioNTech RNA Pharmaceuticals GmbH, and Shanghai Fosun Pharmaceutical Development, Inc.)
Conflict of interest: Yes
Methods | |
RCT | |
Location :
Single center / China Follow-up duration (months): 1.6 | |
•10 mcg BNT126b1 (n= 48)
•30 mcg BNT126b1 (n= 48) •Placebo (n= 48) |
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Inclusion criteria | For adult group (age ?18 and ?55): Male or female subjects of ?18 years old and ?55 years old with body mass index (BMI) ?18 and ?30 at the Screening Visit; Individuals who are in good health condition at the time of entry into the trial as determined by medical history, physical examination (including vital signs, electrocardiogram [ECG]) and eligibility screening test (hematology, blood chemistry and urine analysis) and clinical judgment of the investigator at Screening Visit; The subject can provide with informed consent and signs and dates a written informed consent form (ICF) prior to the initiation of any trial procedures; They must be able to understand and follow trial-related instructions; They must be willing and able to comply with planned visits, treatment schedule, laboratory tests and other requirements of the trial; Negative in antibodies screening of SARS-CoV-2 (fingerstick); Normal in chest computed tomography (CT) scans (no imaging features of COVID-19); Axillary temperature ? 37.0ºC; Negative SARS-CoV-2 test in throat swabs by reverse transcription-polymerase chain reaction (RT-PCR); Women of childbearing potential (WOCBP) must have a negative beta-human chorionic gonadotropin (?-hCG) in serum sample at Screening Visit. Women that are postmenopausal (Menopause?12 consecutive months) or permanently sterilized will be considered as not having reproductive potential; WOCBP must have used effective contraception 14 days prior to screening and agree to use effective contraception continuously during the trial period, from 14 days prior to Screening Visit to 60 days after the last immunization; WOCBP must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during trial, starting from Screening Visit and continuously until 60 days after being given the last immunization; Men who are sexually active with a WOCBP and have not had a vasectomy must agree to practice an effective form of contraception with their female partner of childbearing potential during the trial, starting from Screening Visit and continuously until 60 days after being given the last immunization; Men must be willing to refrain from sperm donation, starting from Screening Visit and continuously until 60 days after receiving the last immunization |
Exclusion criteria | For adult group (age ?18 and ?55): Have had any acute illness, as determined by the investigator, with or without fever, within 72 hours prior to the prime vaccination. An acute illness which is nearly resolved with only minor residual symptoms remaining is allowable if, in the opinion of the investigator, the residual symptoms will not compromise their well-being if they participate as trial subjects in the trial, or that could prevent, limit, or confound the protocol-specified assessments; Are breastfeeding on the day of Screening Visit or who plan to breastfeed during the trial, starting from Screening Visit and continuously until at least 90 days after the last immunization. Women or partners who plan to become pregnant within 1 year post the Screening Visit; Have a known allergy, hypersensitivity, or intolerance to the planned vaccine for trial including any excipients; Used to have a history of hypersensitivity or serious reactions to vaccination; Received any vaccination within 4 weeks prior to Visit 1; Don't agree to not be vaccinated during the trial, starting from Screening Visit and continuously until 28 days after receiving the last immunization, except emergency vaccination (e.g. rabies vaccine, tetanus vaccine); Had any medical condition (e.g., autoimmune disease) or any major surgery (e.g., requiring general anesthesia) within the past 5 years, which in the opinion of the investigator, could compromise their well-being if they participate as trial subjects in the trial, or that could prevent, limit, or confound the protocol-specified assessments; Have any surgery planned during the trial, starting from Screening Visit and continuously until at least 90 days after the last immunization; Had any chronic use (more than 14 continuous days) of any systemic medications that affects immune function, including immunosuppressant or other immune-modifying drugs, within 6 months prior to Screening Visit unless in the opinion of the investigator, the medication would not prevent, limit, or confound the protocol-specified assessments or could compromise safety of subjects; Had administration of any immunoglobulins and/or any blood products within the 3 months prior to Screening Visit; Had administration of another investigational product including vaccines within 60 days or 5 half-lives (whichever is longer), prior to Screening Visit; With known history of AIDS or human immunodeficiency virus (HIV) test positive; History of hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, through medical inquiry; History of SARS, SARS-CoV-2 or middle east respiratory syndrome (MERS) infection. Suspected SARS patients should be screened for SARS antibodies; Previously participated in a clinical trial involving lipid nanoparticles; Are subject to exclusion periods of other clinical trials or simultaneous participation in another clinical trial; Have any affiliation with the study site (e.g., are close relative of the investigator or dependent person, such as an employee or student of the study site); Have a history of drug abuse or known medical, psychological, or social conditions within the past 5 years. In the opinion of the investigator, could comprise their well-being if they participate as trial subjects in the trial, or that could prevent, limit, or confound the protocol-specified assessments; Have a history of narcolepsy; Have history of alcohol abuse or drug addiction within 1 year prior to Screening Visit; Have a history of or suspected immunosuppressive condition, acquired or congenital, as determined by medical history and/or physical examination at Screening Visit; Have any abnormality or permanent body art (e.g., tattoo), that in the opinion of the investigator, would obstruct the ability to observe local reactions at the vaccination site; Have had any blood loss >400 mL, e.g., due to donation of blood or blood products or injury, within the 28 days prior to Screening Visit or plan to donate blood or plasma during the trial, starting from Screening Visit and continuously until at least 28 days after being given the last immunization; Travel or live in any country or region with a high SARS-CoV-2 infection risk (as defined at Screening Visit) within the 14 days prior to Screening Visit; They plan to visit any country or region with a high SARS-CoV-2 infection risk (as defined at Screening Visit), from Screening Visit until 14 days after being given the last immunization; Symptoms of COVID-19, e.g., respiratory symptoms, fever, cough, shortness of breath and breathing difficulties; Have had contact with confirmed COVID-19 patients or persons tested positive for SARS-CoV-2 within the 30 days prior to Screening Visit; Are vulnerable persons, e.g., soldiers, subjects in detention, contract research organization (CRO) or Fosun staff or their family members. |
Interventions | |
Intervention
2 IM doses of 10mcg BNT126b1 per dose, 21 days apart 2 IM doses of 30 mcg BNT126b1 per dose, 21 days apart |
|
Control
2 IM doses of saline, 21 days apart | |
Participants | |
Randomized 144 participants | |
Characteristics of participants Type of participants: Healthy volunteers N=144 72 males Children: 0 Pregnant women: 0 Immunocompromized patients: 0 Mean age: Age range: 18-85 | |
Description of participants Healthy SARS-CoV-2 infection-free adults aged 18-55 and 65-85 at a single center in China | |
Primary outcome | |
In the register 1. Occurrence of solicited local reactions in the subjects (e.g., vaccination sites: pain/tenderness, erythema/redness, induration/swelling) during the 14-days after each dose of BNT162b1 or placebo. [ Time Frame: 14 days following each dose administration ]; 2. Occurrence of solicited systematic reactions (e.g., nausea, vomiting, diarrhea, headache, fatigue, myalgia, arthralgia, chills, loss of appetite, malaise, and fever) during 14-day after each dose of BNT162b1 or placebo. [ Time Frame: 14 days following each dose administration ]; 3. Occurrence of adverse event (AE) associated with vaccination in subjects during the 21-day period after prime vaccination of BNT162b1 or placebo. [ Time Frame: 21-day period after prime vaccination ]; 4. Occurrence of AE associated with vaccination in subjects during the 28-day period after boost dose of BNT162b1 or placebo. [ Time Frame: 28-day period after boost dose ] | |
In the report The primary endpoints for safety evaluation were the incidence of solicited local reactions at the injection site or systemic adverse reactions within 14 days post-vaccination, and adverse events following the full immunization until 28 days after receiving the boost dose. | |
Variants description | |
Variants | |
Description | |
Documents avalaible |
Protocol Yes. In Statistical plan
Data-sharing stated:
Yes, available beginning 3 months and ending 1 year after publication |
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 |
Low |
General comment | In addition to the pre-print article, the trial registries were used in data extraction and assessment of risk of bias. The protocol referred to in the pre-print was not accessible at the time of data extraction. This was an interim analysis of a phase 1 trial. Recruitment is completed and planned sample size has been reached, however, the study is still ongoing for longer term follow-up for some of the outcomes. There were no substantive differences between the pre-print article and the trial registries in population, procedures, interventions or outcomes. |