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 |
OBJECTIVES FOR THE RANDOMIZED OBSERVE-BLINDED PHASE: Primary Efficacy Objectives • To demonstrate 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.
Primary Safety Objectives • To evaluate the safety of CVnCoV administered as a 2-dose schedule to subjects 18 years of age and older. • To evaluate the reactogenicity of CVnCoV administered as a 2-dose schedule to subjects 18 years of age and older participating in Phase 2b of the trial.
OBJECTIVES FOR THE OPEN-LABEL PHASE: Primary Safety Objective: • To evaluate safety in all subjects ≥ 18 years of age remaining in the trial after unblinding |
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E.2.2 | Secondary objectives of the trial |
SECONDARY OBJECTIVES FOR THE RANDOMIZED OBSERVE-BLINDED PHASE: Key Secondary Efficacy Objectives • To demonstrate the efficacy of a 2-dose schedule of CVnCoV in the prevention of first episodes of virologically-confirmed moderate to severe cases of COVID-19 in SARS CoV-2 naïve subjects. • To demonstrate the efficacy of a 2-dose schedule of CVnCoV in the prevention of first episodes of virologically-confirmed severe cases of COVID-19 in SARS-CoV-2 naïve subjects. • To demonstrate 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 caused by "wild type" (i.e., WT/D614G lineages A.1/B.1 without the variant of concern [VOC] B.1.1.7 [Alpha], B.1.351 [Beta], B.1.429 [Epsilon]) and "UK" (B.1.1.7 [Alpha]) SARS CoV 2 strains in SARS CoV 2 naïve subjects.
SECONDARY OBJECTIVES FOR THE OPEN-LABEL PHASE: None.
For full list see protocol. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
INCLUSION CRITERIA FOR ALL SUBJECTS: 1. Male or female subjects 18 years of age or older. 2. Be willing and able to provide written informed consent prior to initiation of any trial procedures 3. Expected compliance with protocol procedures and availability for clinical follow-up through the last planned visit. 4. 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. 5. 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.
Full list of inclusion criteria is provided in the protocol.
ROLL-OVER CRITERIA FOR THE OPEN-LABEL PHASE: 1. Subjects must have received at least 1 dose of CVnCoV during the randomized observer blinded phase. 2. Subjects must provide additional written informed consent to be eligible for the open label phase. • Cohort A: CVnCoV-AV 3. Subjects of the CVnCoV treatment arm who received or will receive any AV as standard of care through their national vaccination program. • Cohort B: CVnCoV only 3. Subjects have not received any vaccination with any other investigational/authorized SARS CoV-2 vaccine or another coronavirus (SARS CoV, MERS-CoV) vaccine |
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E.4 | Principal exclusion criteria |
EXCLUSION CRITERIA FOR ALL SUBJECTS: 1. History of virologically-confirmed COVID-19 illness. 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 or any other 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.
Full list of exclusion criteria is provided in the protocol
ROLL-OVER CRITERIA FOR THE OPEN-LABEL PHASE: 1. Subjects must have received at least 1 dose of CVnCoV during the randomized observer blinded phase. 2. Subjects must provide additional written informed consent to be eligible for the open label phase. • Cohort A: CVnCoV-AV 3. Subjects of the CVnCoV treatment arm who received or will receive any AV as standard of care through their national vaccination program. • Cohort B: CVnCoV only 3. Subjects have not received any vaccination with any other investigational/authorized SARS CoV-2 vaccine or another coronavirus (SARS CoV, MERS-CoV) vaccine |
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E.5 End points |
E.5.1 | Primary end point(s) |
END POINTS FOR THE RANDOMIZED OBSERVE-BLINDED PHASE: Primary Efficacy Endpoints • Occurrence of first episodes of virologically-confirmed (RT-PCR positive) cases of COVID-19 of any severity meeting the case definition for the primary efficacy analysis.
Primary Safety Endpoints All safety endpoints will be analyzed in all subjects, in subjects seronegative at baseline, and in subjects seropositive at baseline. • 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 throughout the trial in all subjects. • Occurrence of fatal SAEs throughout the trial in all subjects. • Occurrence, intensity, and duration of each solicited local AE within 7 days after each trial vaccination in Phase 2b subjects. • Occurrence, intensity, duration of each solicited systemic AE within 7 days after each trial vaccination in Phase 2b subjects. • Occurrence, intensity and relationship of unsolicited AEs occurring within 28 days after each trial vaccination in Phase 2b subjects. • Occurrence of AEs leading to vaccine withdrawal or trial discontinuation throughout the trial in all subjects.
ENDPOINTS FOR THE OPEN-LABEL PHASE: • Occurrence, intensity, and relationship to CVnCoV of SAEs and AESIs collected throughout the trial until the end of trial (EOT). • Occurrence of fatal SAEs throughout the trial until EOT. • Only for Cohort A: CVnCoV-AV: Occurrence of AEs leading to AV withdrawal or trial discontinuation after the first dose with an AV in the open-label phase until EOT
Open-label Exploratory Endpoint • Occurrence of first episodes of symptomatic virologically-confirmed (RT-PCR positive) cases of COVID-19 of any severity as assessed by the Investigator. Any further modifications to endpoints in the open-label phase will be described in the statistical analysis plan (SAP). |
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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 END POINTS FOR THE RANDOMIZED OBSERVE-BLINDED PHASE ONLY: Key Secondary Efficacy Endpoints • Occurrence of first episodes of virologically-confirmed (RT-PCR positive) cases of moderate to severe COVID-19 meeting the case definition for the primary efficacy analysis (moderate and severe COVID-19 disease is defined in Appendix 3 and Appendix 4). • Occurrence of first episodes of virologically-confirmed (RT-PCR positive) severe cases of COVID-19 (meeting the case definition for the primary efficacy analysis (severe COVID-19 disease defined in Appendix 3). •Occurrence of first episodes of virologically-confirmed (RT-PCR positive) cases of COVID-19 of any severity meeting the case definition due to infection with "wild type" (i.e., WT/D614G lineages A.1/B.1 without VOC B.1.1.7 [Alpha], B.1.351 [Beta], B.1.429 [Epsilon]) and "UK" (B.1.1.7 [Alpha]) SARS CoV 2 strains in SARS CoV 2 naïve subjects.
Secondary Immunogenicity Endpoints (Phase 2b Immunogenicity Subset) SARS-CoV-2 (RBD) of S protein antibody responses On Days 1, 29, 43, 120 and 393: • Serum antibodies to SARS-CoV-2 S protein. • Occurrence of seroconversion to SARS-CoV-2 S protein. Seroconversion is defined as detectable SARS-CoV-2 S protein antibodies in the serum of subjects who tested seronegative at baseline.
SARS-CoV-2 viral neutralizing antibody responses On Days 1, 29, 43, 120 and 393: • Serum neutralizing antibodies to SARS-CoV-2 virus, as measured by a viral neutralizing antibody assay. • Occurrence of seroconversion to SARS-CoV-2 virus, as measured by a viral neutralizing antibody assay. Seroconversion is defined as detectable SARS-CoV-2 viral neutralizing antibodies in the serum of subjects who tested seronegative at baseline.
Full list of secondary end points is provided in the protocol. |
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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 | No |
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) | Yes |
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 |
Randomized observer-blinded followed by an Open Label Phase |
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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
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 13 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Colombia |
Dominican Republic |
Mexico |
Panama |
Peru |
Argentina |
Belgium |
Germany |
Netherlands |
Spain |
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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 | |
E.8.9.1 | In the Member State concerned months | 13 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 13 |