A Study to Determine the Safety and Efficacy of SARS-CoV-2 mRNA Vaccine CVnCoV in Adults for COVID-19

Study Overview
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Brief Summary
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The primary objective of the randomized observer-blinded phase 2b/3 part of this trial is 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 participants. The primary objective of the open-label phase of this trial is to evaluate safety in all participants ≥ 18 years of age remaining in the trial after unblinding.

Detailed Description
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This clinical trial information was submitted voluntarily under the applicable law and, therefore, certain submission deadlines may not apply. (That is, clinical trial information for this applicable clinical trial was submitted under section 402(j)(4)(A) of the Public Health Service Act and 42 CFR 11.60 and is not subject to the deadlines established by sections 402(j)(2) and (3) of the Public Health Service Act or 42 CFR 11.24 and 11.44.).

Official Title
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COVID-19: A Phase 2b/3, Randomized, Observer-Blinded, Placebo-Controlled, Multicenter Clinical Study Evaluating the Efficacy and Safety of Investigational SARS-CoV-2 mRNA Vaccine CVnCoV in Adults 18 Years of Age and Older

Conditions
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Covid19, SARS-CoV-2

Intervention / Treatment
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* Biological: CVnCoV
* Biological: Placebo
* Biological: Authorized/licensed vaccines for preventing COVID-19 (AV)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female participants 18 years of age or older. Be 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. The following methods of birth control are considered highly effective when used consistently and correctly: Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal or transdermal); Progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable or implantable); Intrauterine devices; Intrauterine hormone-releasing systems; Bilateral tubal ligation; Vasectomized or infertile partner; Sexual abstinence {periodic abstinence (e.g., calendar, ovulation, symptothermal and post-ovulation methods) and withdrawal are not acceptable}. 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). These include severe and/or uncontrolled cardiovascular disease, gastrointestinal disease, liver disease, renal disease, respiratory disease, endocrine disorder, and neurological and psychiatric illnesses. However, those with controlled and stable cases can be included in the trial. Participants with impaired coagulation or any bleeding disorder in whom an IM injection or a blood draw is contraindicated. Foreseeable non-compliance with the trial procedure as judged by the Investigator. Roll-over Criteria for the Open-label Phase: Participants must have received at least 1 dose of CVnCoV during the randomized observer blinded phase. Participants must provide additional written informed consent to be eligible for the open label phase.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Randomized Observer-blinded Phase 2b: CVnCoV vaccine<br>Participants will be vaccinated with CVnCoV 12 µg vaccine on Day 1 and Day 29 in the deltoid area, preferably in the non-dominant arm. | Biological: CVnCoV<br>* Intramuscular (IM) injection.<br>* Other names: CV07050101;|
| Placebo Comparator: Randomized Observer-blinded Phase 2b: Placebo<br>Participants will be administered the matching placebo on Day 1 and Day 29 in the deltoid area, preferably in the non-dominant arm. | Biological: Placebo<br>* Intramuscular (IM) injection.<br>|
| Experimental: Randomized Observer-blinded Phase 3: CVnCoV vaccine<br>Participants will be vaccinated with CVnCoV 12 µg vaccine on Day 1 and Day 29 in the deltoid area, preferably in the non-dominant arm. | Biological: CVnCoV<br>* Intramuscular (IM) injection.<br>* Other names: CV07050101;|
| Placebo Comparator: Randomized Observer-blinded Phase 3: Placebo<br>Participants will be administered the matching placebo on Day 1 and Day 29 in the deltoid area, preferably in the non-dominant arm. | Biological: Placebo<br>* Intramuscular (IM) injection.<br>|
| Experimental: Open-label Phase<br>After unblinding, the trial will shift from a randomized observer-blinded to an open-label design, and the following cohorts will be defined: Cohort A: participants who received at least 1 dose of CVnCoV in the randomized observer-blinded phases and choose to receive an authorized/licensed vaccine for preventing COVID-19 (AV) as standard of care through their national vaccination program. Cohort B: participants who received at least 1 dose of CVnCoV in the randomized observer-blinded phases and choose to remain in the trial without receiving any AV. Participants on the placebo arm will be withdrawn. | Biological: Authorized/licensed vaccines for preventing COVID-19 (AV)<br>* Intramuscular (IM) injection will be received as standard of care (SoC) outside the study.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 |  | Day 1 to Day 393 | 
| Number of participants who experience one or more medically-attended adverse events (AEs) |  | Day 29 to Day 211 | 
| Intensity grading of medically-attended adverse events (AEs) as per adapted Food and Drug Administration (FDA) classification | The adapted FDA classification will grade AEs on a grade of 0 to 3. Higher grades indicate a worse outcome. | Day 29 to Day 211 | 
| Number of participants who experience one or more treatment-related medically-attended adverse events (AEs) |  | Day 29 to Day 211 | 
| Number of participants who experience one or more serious adverse events (SAEs) |  | Day 1 to Day 393 | 
| Intensity grading of serious adverse events (SAEs) as per adapted FDA classification | The adapted FDA classification will grade SAEs on a grade of 0 to 3. Higher grades indicate a worse outcome. | Day 1 to Day 393 | 
| Number of participants who experience one or more treatment-related serious adverse events (SAEs) |  | Day 1 to Day 393 | 
| Number of participants who experience one or more adverse events of special interest (AESI) |  | Day 1 to Day 393 | 
| Intensity grading of adverse events of special interest (AESI) as per adapted FDA classification | The adapted FDA classification will grade AESI on a grade of 0 to 3. Higher grades indicate a worse outcome. | Day 1 to Day 393 | 
| Number of participants who experience one or more treatment-related adverse events of special interest (AESI) |  | Day 1 to Day 393 | 
| Number of participants who experience a fatal serious adverse event (SAE) |  | Day 1 to Day 393 | 
| Number of participants who experience an adverse event (AE) leading to authorized/licensed vaccines withdrawal or trial discontinuation after first dose with an authorized/licensed vaccine for preventing COVID-19 (AV) administered | Measured in the open-label phase, Cohort A only. | Day 1 to Day 393 | 
| Phase 2b participants only: Number of participants who experience one or more solicited local adverse events (AEs) |  | 7 days after vaccination | 
| Phase 2b participants only: Intensity grading of solicited local adverse events (AEs) as per adapted FDA classification | The adapted FDA classification will grade AEs on a grade of 0 to 3. Higher grades indicate a worse outcome. | 7 days after vaccination | 
| Phase 2b participants only: Duration of solicited local adverse events (AEs) |  | 7 days after vaccination | 
| Phase 2b participants only: Number of participants who experience one or more solicited systemic adverse events (AE) |  | 7 days after vaccination | 
| Phase 2b participants only: Intensity grading of solicited systemic adverse events (AEs) as per adapted FDA classification | The adapted FDA classification will grade AEs on a grade of 0 to 3. Higher grades indicate a worse outcome. | 7 days after vaccination | 
| Phase 2b participants only: Duration of solicited systemic adverse events (AEs) |  | 7 days after vaccination | 
| Phase 2b participants only: Number of participants who experience one or more unsolicited adverse events (AEs) |  | 28 days after vaccination | 
| Phase 2b participants only: Intensity grading of unsolicited adverse events (AEs) as per adapted FDA classification | The adapted FDA classification will grade AEs on a grade of 0 to 3. Higher grades indicate a worse outcome. | 28 days after vaccination | 
| Phase 2b participants only: Number of participants who experience one or more treatment-related unsolicited adverse events (AEs) |  | 28 days after vaccination | 
| Number of participants who experience one or more adverse events (AEs) leading to vaccine withdrawal or trial discontinuation |  | Day 1 to Day 393 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants who experience a first episode of virologically-confirmed {reverse transcription polymerase chain reaction (RT-PCR) positive} moderate to severe case of COVID-19 |  | Day 1 to Day 393 | 
| Number of participants who experience a first episode of virologically-confirmed {reverse transcription polymerase chain reaction (RT-PCR) positive} severe case of COVID-19 |  | Day 1 to Day 393 | 
| 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 due to infection with wild type and UK SARS-CoV-2 strains | Measured in SARS-CoV-2 naïve participants. | Day 1 to Day 393 | 
| Number of participants aged ≥ 61 who experience a first episode of virologically-confirmed {reverse transcription polymerase chain reaction (RT-PCR) positive} case of COVID-19 of any severity |  | Day 1 to Day 393 | 
| Number of participants who experience a virologically-confirmed {reverse transcription polymerase chain reaction (RT-PCR) positive} SARS-CoV-2 infection, with or without symptoms |  | Day 1 to Day 393 | 
| Burden of disease (BoD) based on first episodes of virologically-confirmed {reverse transcription polymerase chain reaction (RT-PCR) positive} cases of COVID-19 |  | Day 1 to Day 393 | 
| Number of participants who experience a virologically-confirmed {reverse transcription polymerase chain reaction (RT-PCR) positive} case of COVID-19 of any severity with symptom onset at any time after the first study vaccination |  | Post vaccination on Day 1 up to Day 393 | 
| Number of participants with serum antibodies to SARS-CoV-2 spike (S) protein | S protein will be measured by enzyme-linked immunosorbent assay (ELISA). | Days 1, 29, 43, 120 and 211 | 
| Number of participants who experience seroconversion to SARS-CoV-2 spike (S) protein | S protein will be measured by enzyme-linked immunosorbent assay (ELISA). Seroconversion is defined as detectable SARS-CoV-2 S protein antibodies in the serum of participants who tested seronegative on Day 1. | Days 1, 29, 43, 120 and 211 | 
| Number of participants with serum vital neutralizing antibodies to SARS-CoV-2 virus | Serum vital neutralizing antibodies to SARS-CoV-2 virus will be measured by a viral neutralizing antibody assay. | Days 1, 29, 43, 120 and 211 | 
| Number of participants who experience seroconversion to SARS-CoV-2 virus | Seroconversion to SARS-CoV-2 virus will be measured by a viral neutralizing antibody assay. Seroconversion is defined as detectable SARS-CoV-2 viral neutralizing antibodies in the serum of participants who tested seronegative on Day 1. | Days 1, 29, 43, 120 and 211 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vaccine