COVID-19: A Study to Evaluate Safety, Reactogenicity and Immunogenicity of the SARS-CoV-2 mRNA Vaccine CVnCoV in Adults With Co-morbidities
Condition: Coronavirus; Covid19; SARS-CoV-2; Severe Acute Respiratory Syndrome
MeSH terms: COVID-19; Severe Acute Respiratory Syndrome
Intervention: CVnCoV Vaccine
Intervention description: Intramuscular (IM) injection in the deltoid area, preferably in the non-dominant arm.
Phase: Phase 3
Study type: Interventional
Primary purpose: Prevention
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 129.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Covid19; CVnCoV; SARS-CoV-2 mRNA vaccine; Vaccine; SARS; COVID; Safety; Reactogenicity; Immunogenicity

Summary:

      The primary objectives of this study are to evaluate the safety and reactogenicity profile
      after 1 and 2 dose administrations of investigational SARS-CoV-2 mRNA vaccine CVnCoV, and to
      evaluate the humoral immune responses 14 days after 2 dose administrations of CVnCoV.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Male and female participants ≥18 years of age with 1 or more co-morbidities.

          2. For the co-morbidities chronic kidney disease, chronic obstructive pulmonary disease
             (COPD), chronic cardiovascular disease and diabetes mellitus, the first 25
             participants per co-morbidity should include only mild to moderate cases. Thereafter,
             more severe conditions may be recruited following Internal Safety Review Committee
             (iSRC) and Data Safety Monitoring Board (DSMB) Chair approval.

          3. Participant has no overt clinical signs or symptoms of COVID-19.

          4. Participant has to sign the informed consent form (ICF) before any trial procedures.

          5. Participants with a life expectancy of at least 1 year as per the Investigator's
             assessment.

          6. Expected to be compliant with protocol procedures and available for clinical follow-up
             through the last planned visit.

          7. Physical examination without acute clinically significant findings according to the
             Investigator's assessment.

          8. Female participants: At the time of enrollment, negative human chorionic gonadotropin
             (hCG) pregnancy test (serum) for women presumed to be of childbearing potential on the
             day of enrollment. On Day 1 (pre vaccination): negative urine pregnancy test (hCG)
             (only required if serum pregnancy test was performed more than 3 days before).

             Note: Women that are postmenopausal (defined as amenorrhea for ≥ 12 consecutive months
             prior to screening without an alternative medical cause) or permanently sterilized
             will be considered as not having reproductive potential.

          9. Female participants 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:

          1. A previous clinical and laboratory-confirmed diagnosis of COVID-19 within the last six
             months prior to screening.

          2. Use of any investigational or non-registered product (vaccine or drug) other than the
             trial vaccine within 28 days preceding the administration of the trial vaccine, or
             planned use during the trial period.

          3. Receipt of any other vaccines within 28 days prior to enrollment in this trial or
             planned receipt of any vaccine within 28 days of trial vaccine administration. Planned
             vaccination with an inactivated influenza vaccine is permitted.

          4. Receipt of any investigational, authorized or licensed SARS-CoV-2, other coronavirus
             vaccine or any other lipid nanoparticles (LNP)-containing messenger ribonucleic acid
             vaccine prior to the administration of the trial vaccine. For authorized or licensed
             SARS-CoV-2: planned administration during the trial up to 6 weeks after the foreseen
             date of second dose administration of CVnCoV.

          5. Any treatment with immunosuppressants or other immune-modifying drugs (including, but
             not limited to, corticosteroids, biologicals, and methotrexate) for >14 days in total
             within 6 months prior to the administration of the 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.

             Note: This exclusion does not apply to the renal transplant cases and is at the
             Investigator's discretion for participants with other co-morbidities (e.g., COPD).

          6. Participants with chronic human immunodeficiency virus (HIV) infection with controlled
             Hepatitis B infection with therapy or aviremic Hepatitis C may be eligible for the
             trial, based on the Investigator's judgment.

          7. History of immune-mediated or autoimmune disease.

          8. History of anaphylaxis or allergy to any component of CVnCoV or aminoglycoside
             antibiotics.

          9. History of or current alcohol and/or drug abuse.

         10. History of confirmed severe acute respiratory syndrome (SARS) or Middle East
             respiratory syndrome (MERS) disease.

         11. Administration of immunoglobulins and/or any blood products within the 3 months
             preceding the administration of any dose of the trial vaccine.

         12. Presence or evidence of significant uncontrolled acute or chronic medical or
             psychiatric illness, excluding the co-morbidities specified in the protocol.
             Significant medical or psychiatric illnesses include but are not limited to:

               -  Uncontrolled respiratory disease.

               -  Uncontrolled neurological disorders or Guillain-Barré syndrome or history of
                  seizure, except for febrile seizures during childhood.

               -  Current or past malignancy, unless completely resolved without sequelae for >5
                  years

         13. Foreseeable non-compliance with protocol, as judged by the Investigator.

         14. For female participants: pregnancy or lactation.

         15. Participants with impaired coagulation or any bleeding disorder in whom an IM
             injection or a blood draw is contraindicated. This includes participants on treatment
             with anticoagulants (e.g., vitamin K antagonists, novel oral anticoagulants, and
             heparin). Use of platelet aggregation inhibitors is not exclusionary. However, use of
             anticoagulants is accepted in certain co-morbidities according to the clinical
             Investigator's judgment and if the international normalized ratio (INR) remains ≤3.

         16. Participants employed by the Sponsor, Investigator, or trial site, or relatives of
             research staff working on this trial.