Trial NCT04652102; EudraCT 2020-003998-22
Publication Kremsner P, Lancet Infect Dis, 2022
Dates: 2020-12-11 to 2021-04-12
Funding: Mixed (The German Federal Ministry of Education and Research (BMBF), CureVac AG)
Conflict of interest: Yes
| Methods | |
| RCT | |
| Location :
Multicenter / Belgium, Germany, The Netherlands, Spain, Argentina, Colombia, Dominican Republic, Mexico, Panama, Peru Follow-up duration (months): 6.23 | |
| 12 mcg CVnCoV (n=19846) Placebo (n=19834) | |
| Inclusion criteria | Male or female participants 18 years of age or older; willing and able to provide written informed consent prior to initiation of any trial procedures; Expected compliance with protocol procedures and availability for clinical follow-up through the last planned visit; Females of non-childbearing potential defined as follows: surgically sterile (history of bilateral tubal ligation/occlusion, bilateral oophorectomy or hysterectomy) or postmenopausal {defined as amenorrhea for ≥12 consecutive months prior to screening (Day 1) without an alternative medical cause}. A follicle-stimulating hormone (FSH) level may be measured at the discretion of the Investigator to confirm postmenopausal status; Females of childbearing potential: negative pregnancy test (human chorionic gonadotropin [hCG]) within 24 hours prior to each trial vaccination on Day 1 and Day 29; Females of childbearing potential must use highly effective methods of birth control from 2 weeks before the first administration of the trial vaccine until 3 months following the last administration |
| Exclusion criteria | History of virologically-confirmed COVID-19 illness; For females: pregnancy or lactation; Use of any investigational or non-registered product (vaccine or drug) within 28 days preceding the administration of trial vaccine or planned use during the trial; Receipt of any licensed vaccines within 28 days (for live vaccines) or 14 days (for inactivated or any other vaccines) prior to administration of the first trial vaccine; Prior administration of any investigational SARS-CoV-2 vaccine or another coronavirus (SARS-CoV, Middle East Respiratory Syndrome-CoV) vaccine or planned used during the trial; Any treatment with immunosuppressants or other immune-modifying drugs (including but not limited to anabolic steroids, corticosteroids, biologicals and methotrexate) for > 14 days total within 6 months preceding the administration of trial vaccine or planned use during the trial. For corticosteroid use, this means prednisone or equivalent, 0.5 mg/kg/day for 14 days or more. The use of inhaled, topical, or localized injections of corticosteroids (e.g., for joint pain/inflammation) is permitted; Any medically diagnosed or suspected immunosuppressive or immunodeficient condition based on medical history and physical examination including known infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV); current diagnosis of or treatment for cancer including leukemia, lymphoma, Hodgkin disease, multiple myeloma or generalized malignancy; chronic renal failure or nephrotic syndrome; and receipt of an organ or bone marrow transplant; History of angioedema (hereditary or idiopathic) or history of any anaphylactic reaction; History of potential immune-mediated disease (pIMD); History of allergy to any component of CVnCoV; Administration of immunoglobulins or any blood products within 3 months prior to the administration of trial vaccine or planned receipt during the trial; Participants with a significant acute or chronic medical or psychiatric illness that, in the opinion of the Investigator, precludes trial participation (e.g., may increase the risk of trial participation, render the participant unable to meet the requirements of the trial, or may interfere with the participant's trial evaluations); Participants with impaired coagulation or any bleeding disorder in whom an intramuscular injection or a blood draw is contraindicated; Foreseeable non-compliance with the trial procedure as judged by the Investigator. |
| Interventions | |
| Intervention
2 IM doses of 12 mcg, 28 days apart |
|
| Control
2 IM doses, 28 days apart | |
| Participants | |
| Randomized 39680 participants | |
| Characteristics of participants Type of participants: Adults N=39680 21672 males Children: 0 Pregnant women: 0 Immunocompromized patients: 0 Mean age: Age range: 18-98 | |
| Description of participants Adults with no history of COVID-19 in 47 centers in Belgium, Germany, The Netherlands, Spain, Argentina, Colombia, Dominican Republic, Mexico, Panama and Peru | |
| Primary outcome | |
| In the register 1. Number of participants who experience a first episode of virologically-confirmed {reverse transcription polymerase chain reaction (RT-PCR) positive} case of COVID-19 of any severity [ Time Frame: Day 1 to Day 393 ]; 2. Number of participants who experience one or more medically-attended adverse events (AEs) [ Time Frame: Day 29 to Day 211 ]; 3. Intensity grading of medically-attended adverse events (AEs) per FDA toxicity grading scale [ Time Frame: Day 29 to Day 211 ]; 4. Number of participants who experience one or more treatment-related medically-attended adverse events (AEs) [ Time Frame: Day 29 to Day 211 ]; 5. Number of participants who experience one or more serious adverse events (SAEs) [ Time Frame: Day 29 to Day 393 ]; 6. Intensity grading of serious adverse events (SAEs) per FDA toxicity grading scale [ Time Frame: Day 29 to Day 393 ]; 7. Number of participants who experience one or more treatment-related serious adverse events (SAEs) [ Time Frame: Day 29 to Day 393 ]; 8. Number of participants who experience one or more adverse events of special interest (AESI) [ Time Frame: Day 29 to Day 393 ]; 9. Intensity grading of adverse events of special interest (AESI) per FDA toxicity grading scale [ Time Frame: Day 29 to Day 393 ]; 10. Number of participants who experience one or more treatment-related adverse events of special interest (AESI) [ Time Frame: Day 29 to Day 393 ]; 11. Number of participants who experience a fatal serious adverse event (SAE) [ Time Frame: Day 29 to Day 393 ] | |
| In the report The occurrence of a first episode of virologically confirmed symptomatic COVID-19 of any severity and caused by any strain from 15 days after the second dose up to 1 year. | |
| Variants description | |
Variants
| |
| Description Efficacy results reported by alpha, gamma, lambda, B.1.621 (Colombia), and Other (table 2); efficacy against strains was evaluated in adjudicated and sequenced cases in participants aged 18–60 years; only 3% of all sequenced COVID-19 cases were wild type | |
| Documents avalaible |
Protocol NR Statistical plan * Data-sharing stated:
Yes, From when the trial is complete for a minimum of five years from the end of the trial |
| 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 prospective registry and the supplementary material were used in data extraction and assessment of risk of bias. Neither protocol nor statistical analysis plan was available. Follow-up is ongoing, the cut-off date for this analysis was 18 June 2021. In this report the primary outcome broadly reflects that in the protocol, except that in the registry the timeframe for a first episode of virologically-confirmed COVID-19 is Day 1 to Day 393 whereas in the report this is from two weeks after the second dose. The study achieved its modified event-driven target sample size. The number analyzed for COVID events was substantially reduced because participants were allowed to be unblinded when they became eligible for a licensed vaccine and were subsequently excluded from efficacy analyses. This trial was updated on Mar 3rd, 2022 after publication of the study report. |