E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Vaccination for prophylaxis of COVID-19 (healthy adults) |
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E.1.1.1 | Medical condition in easily understood language |
Prophylactic vaccine against COVID-19 |
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E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 23.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10084464 |
E.1.2 | Term | COVID-19 immunization |
E.1.2 | System Organ Class | 100000004865 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Primary Safety Objective
• To evaluate the safety (in all subjects) and reactogenicity (in a subset of subjects) of CVnCoV administered as a 2-dose schedule to adults
18 years of age or older.
Primary Immunogenicity Objective
• To assess antibody responses to the Receptor-binding domain (RBD) of S protein of SARS-CoV-2 after 1 and 2 doses of CVnCoV in adults 18 years of age or older included in a subset of subjects. |
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E.2.2 | Secondary objectives of the trial |
• To assess the efficacy of a 2-dose schedule of CVnCoV in the prevention of first episodes of virologically-confirmed cases of COVID-19 of any
severity in SARS-CoV-2 naïve subjects.
• To describe the severity of first episodes of virologically-confirmed cases of COVID-19 in SARS-CoV-2 naïve subjects, receiving a 2-dose
schedule of CVnCoV compared to those administered placebo.
• To assess the efficacy of a 2-dose schedule of CVnCoV in the prevention or reduction of asymptomatic infection by SARS-CoV-2 in seronegative
subjects, as measured by seroconversion to the N protein of the virus.
• To assess the efficacy of a 2-dose schedule of CVnCoV in reducing the burden of disease (BoD) from COVID-19.
Secondary Immunogenicity Objectives
• To assess SARS-CoV-2 virus neutralizing antibody responses after 1 and 2 doses of CVnCoV in adults 18 years of age or older.
• To assess lot-to-lot consistency of 2 CVnCoV lots, after 2 doses of CVnCoV, in adults 18 years of age or older. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or female subjects 18 years of age or older.
2. HCWs, employees or students in the clinical years.
3. Provide written informed consent prior to initiation of any trial procedures.
4. Expected compliance with protocol procedures and availability for clinical follow-up through the last planned visit.
The full list of inclusion criteria is provided in the protocol. |
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E.4 | Principal exclusion criteria |
1. History of virologically-confirmed SARS-CoV-2 infection or SARS-CoV-2 positive serology.
2. For females: pregnancy or lactation.
3. Use of any investigational or non-registered product (vaccine or drug) within 28 days preceding the administration of the first trial vaccine or planned use during the trial.
4. Receipt of licensed vaccines within 28 days (for live vaccines) or 14 days (for inactivated vaccines) prior to the administration of the first trial vaccine.
5. Prior administration of any investigational SARS-CoV-2 vaccine or another coronavirus (SARS-CoV, MERS-CoV) vaccine or planned use during the trial.
The full list of exclusion criteria is provided in the protocol. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary Safety Endpoints
• Occurrence, intensity and relationship of medically-attended AEs collected through 6 months after the second trial vaccination in all subjects.
• Occurrence, intensity and relationship of SAEs and AESIs collected through 1 year after the second trial vaccination in all subjects.
• Occurrence of fatal SAEs through 1 year after the second trial vaccination in all subjects.
• Occurrence of AEs leading to vaccine withdrawal or trial discontinuation through 1 year after the second trial vaccination in all subjects.
• Occurrence, intensity and duration of each solicited local AE within 7 days after each trial vaccination in a subset of subjects.
• Occurrence, intensity, duration of each solicited systemic AE within 7 days after each trial vaccination in a subset of subjects.
• Occurrence, intensity and relationship of unsolicited AEs occurring within 28 days after each trial vaccination in a subset of subjects.
Primary Immunogenicity Endpoint
SARS-CoV-2 RBD of S protein antibody responses in a subset of subjects
On Days 1, 29, 43, 57, 120, 211 and 393:
• Serum antibodies to SARS-CoV-2 RBD of S protein.
• Occurrence of seroconversion to SARS-CoV-2 RBD of S protein.
- Seroconversion is defined as detectable SARS-CoV-2 RBD of S protein antibodies in the serum of subjects who tested seronegative at baseline. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
as specified in the endpoints |
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E.5.2 | Secondary end point(s) |
Secondary Efficacy Endpoints
• Occurrence of first episodes of virologically-confirmed (RT-PCR) cases of COVID-19 of any severity meeting the case definition for the efficacy analysis.
• Occurrence of first episodes of virologically-confirmed (RT-PCR positive) cases of COVID-19 meeting the case definition for the efficacy analysis by severity (mild, moderate, severe and moderate to severe COVID-19) as defined in Appendix 3 and Appendix 4.
• Occurrence of seroconversion to the N protein of SARS-CoV-2 ≥ 15 days following the second trial vaccination in asymptomatic
seronegative subjects.
- Seroconversion is defined as detectable SARS-CoV-2 N Protein antibodies in the serum of subjects on Day 211 and/or Day 393 of the trial, who tested seronegative at Day 1 (baseline) and Day 43 (i.e. at the 2 testing time points prior to 15 days after the second trial vaccination).
• BoD scores calculated based on first episodes of virologically-confirmed (RT-PCR positive) cases of COVID-19 of any severity meeting the case definition for the efficacy Analysis.
- BoD #1 – no disease (not infected or asymptomatic infection) = 0; mild or moderate disease = 1; severe disease = 2.
- BoD #2 – no disease (not infected or asymptomatic infection) = 0; disease without hospitalization = 1; disease with hospitalization = 2; death = 3
Secondary Immunogenicity Endpoints
SARS-CoV-2 virus neutralizing antibody responses in a subset of subjects
On Days 1, 29, 43, 57, 120, 211 and 393:
• Serum neutralizing antibodies to SARS-CoV-2 virus, as measured by a virus neutralizing assay.
• Occurrence of seroconversion to SARS-CoV-2 virus, as measured by a virus neutralizing assay.
- Seroconversion is defined as detectable SARS-CoV-2 Virus neutralizing antibodies in the serum of subjects who tested seronegative at baseline.
Lot-to-lot consistency of 2 CVnCoV lots, as measured by SARS-CoV-2 RBD of S protein antibody responses in a subset of subjects
On Days 43, 57, 120, 211 and 393:
• Serum antibodies to SARS-CoV-2 RBD of S protein. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
as specified in the endpoints |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | |