A Study to Evaluate the Safety and Immunogenicity of Vaccine CVnCoV in Healthy Adults in Germany for COVID-19

• ClinicalTrials.gov Identifier: NCT04674189
• Recruitment Status: Completed
• First Posted: December 19, 2020
• Last Update Posted: June 22, 2022
• Sponsor: CureVac AG
• Collaborator: German Federal Ministry of Education and Research
• Information provided by (Responsible Party): CureVac AG

Tracking Information

• First Submitted Date: December 14, 2020
• First Posted Date: December 19, 2020
• Last Update Posted Date: June 22, 2022
• Actual Study Start Date: December 23, 2020
• Actual Primary Completion Date: June 8, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 8, 2022)

• Number of Participants with Medically-attended Adverse Events [ Time Frame: Day 29 to Day 211 ]
• Intensity of Medically-attended Adverse Events per Investigator's Assessment [ Time Frame: Day 29 to Day 211 ]
• Number of Participants with Medically-attended Adverse Events Considered Related to Trial Vaccine [ Time Frame: Day 29 to Day 211 ]
• Number of Participants with One or More Serious Adverse Events (SAEs) [ Time Frame: Day 29 to Day 393 ]
• Intensity of Serious Adverse Events (SAEs) per Investigator's Assessment [ Time Frame: Day 29 to Day 393 ]
• Number of Participants with One or More Serious Adverse Events (SAEs) Considered Related to Trial Vaccine [ Time Frame: Day 29 to Day 393 ]
• Number of Participants with One or More Adverse Events of Special Interest (AESIs) [ Time Frame: Day 29 to Day 393 ]
• Intensity of Adverse Events of Special Interest (AESIs) per Investigator's Assessment [ Time Frame: Day 29 to Day 393 ]
• Number of Participants with One or More Serious Adverse Events of Special Interest (AESIs) Considered Related to Trial Vaccine [ Time Frame: Day 29 to Day 393 ]
• Number of Participants with Death due to a Serious Adverse Event (SAE) [ Time Frame: Day 29 to Day 393 ]
• Number of Participants with Adverse Events (AEs) Leading to Vaccine Withdrawal or Study Discontinuation [ Time Frame: Day 29 to Day 393 ]
• Number of Participants with Solicited Local Adverse Events [ Time Frame: 7 days after vaccination ]
• Intensity of Solicited Local Adverse Events per the FDA Toxicity Grading Scale [ Time Frame: 7 days after vaccination ]
• Duration of Solicited Local Adverse Events [ Time Frame: 7 days after vaccination ]
• Number of Participants with Solicited Systemic Adverse Events [ Time Frame: 7 days after vaccination ]
• Intensity of Solicited Systemic Adverse Events per the FDA Toxicity Grading Scale [ Time Frame: 7 days after vaccination ]
• Duration of Solicited Systemic Adverse Events [ Time Frame: 7 days after vaccination ]
• Number of Participants with Unsolicited Adverse Events [ Time Frame: 28 days after vaccination ]
• Intensity of Unsolicited Adverse Events per the Investigator's Assessment [ Time Frame: 28 days after vaccination ]
• Number of Participants with Unsolicited Adverse Events Considered Related to Trial Vaccine [ Time Frame: 28 days after vaccination ]
• Individual SARS-CoV-2 Spike (S) Protein-Specific Antibody Levels in Serum [ Time Frame: Days 1, 29 and 43 ]
  Measured using Enzyme-Linked Immunosorbent Assay (ELISA).
• Number of Participants Seroconverting for SARS-CoV-2 Spike (S) Protein Antibodies [ Time Frame: Days 1, 29 and 43 ]
  Measured using Enzyme-Linked Immunosorbent Assay (ELISA). Seroconversion is defined as detectable SARS-CoV-2 RBD of S protein antibodies in the serum of participants who tested seronegative on prior to vaccination on Day 1.

Original Primary Outcome Measures (submitted: December 14, 2020)

• Number of Participants with Medically-attended Adverse Events [ Time Frame: Day 29 to Day 211 ]
• Intensity of Medically-attended Adverse Events per Investigator's Assessment [ Time Frame: Day 29 to Day 211 ]
• Number of Participants with Medically-attended Adverse Events Considered Related to Trial Vaccine [ Time Frame: Day 29 to Day 211 ]
• Number of Participants with One or More Serious Adverse Events (SAEs) [ Time Frame: Day 29 to Day 393 ]
• Intensity of Serious Adverse Events (SAEs) per Investigator's Assessment [ Time Frame: Day 29 to Day 393 ]
• Number of Participants with One or More Serious Adverse Events (SAEs) Considered Related to Trial Vaccine [ Time Frame: Day 29 to Day 393 ]
• Number of Participants with One or More Adverse Events of Special Interest (AESIs) [ Time Frame: Day 29 to Day 393 ]
• Intensity of Adverse Events of Special Interest (AESIs) per Investigator's Assessment [ Time Frame: Day 29 to Day 393 ]
• Number of Participants with One or More Serious Adverse Events of Special Interest (AESIs) Considered Related to Trial Vaccine [ Time Frame: Day 29 to Day 393 ]
• Number of Participants with Death due to a Serious Adverse Event (SAE) [ Time Frame: Day 29 to Day 393 ]
• Number of Participants with Adverse Events (AEs) Leading to Vaccine Withdrawal or Study Disctontinuation [ Time Frame: Day 29 to Day 393 ]
• Number of Participants with Solicited Local Adverse Events [ Time Frame: 7 days after vaccination ]
• Intensity of Solicited Local Adverse Events per the FDA Toxicity Grading Scale [ Time Frame: 7 days after vaccination ]
• Duration of Solicited Local Adverse Events [ Time Frame: 7 days after vaccination ]
• Number of Participants with Solicited Systemic Adverse Events [ Time Frame: 7 days after vaccination ]
• Intensity of Solicited Systemic Adverse Events per the FDA Toxicity Grading Scale [ Time Frame: 7 days after vaccination ]
• Duration of Solicited Systemic Adverse Events [ Time Frame: 7 days after vaccination ]
• Number of Participants with Unsolicited Adverse Events [ Time Frame: 28 days after vaccination ]
• Intensity of Unsolicited Adverse Events per the Investigator's Assessment [ Time Frame: 28 days after vaccination ]
• Number of Participants with Unsolicited Adverse Events Considered Related to Trial Vaccine [ Time Frame: 28 days after vaccination ]
• Individual SARS-CoV-2 Spike (S) Protein-Specific Antibody Levels in Serum [ Time Frame: Days 1, 29, 43, 57, 120, 211 and 393 ]
  Measured using Enzyme-Linked Immunosorbent Assay (ELISA).
• Number of Participants Seroconverting for SARS-CoV-2 Spike (S) Protein Antibodies [ Time Frame: Days 1, 29, 43, 57, 120, 211 and 393 ]
  Measured using Enzyme-Linked Immunosorbent Assay (ELISA). Seroconversion is defined as detectable SARS-CoV-2 RBD of S protein antibodies in the serum of participants who tested seronegative on prior to vaccination on Day 1.

Current Secondary Outcome Measures (submitted: February 8, 2022)

• Number of Participants that Contract COVID-19 of Any Severity [ Time Frame: Day 1 to Day 393 ]
• Number of Participants that Contract Mild, Moderate, Severe and Moderate to Severe COVID-19 [ Time Frame: Day 1 to Day 393 ]
• Burden of Disease (BoD) Score Based on First Episodes of Virologically-confirmed Cases of COVID-19 [ Time Frame: Day 1 to Day 393 ]
• Individual SARS-CoV-2 Neutralizing Antibody Levels in Serum [ Time Frame: Days 1, 29 and 43 ]
  Measured by a virus neutralizing assay in a subset of participants.
• Number of Participants Seroconverting to SARS-CoV-2 [ Time Frame: Days 1, 29 and 43 ]
  Measured by a virus neutralizing assay in a subset of participants.
• Individual Serum Antibodies to Spike (S) Protein of SARS-CoV-2 [ Time Frame: Day 43 ]
  Measured by a virus neutralizing assay in a subset of participants.

Original Secondary Outcome Measures (submitted: December 14, 2020)

• Number of Participants that Contract COVID-19 of Any Severity [ Time Frame: Day 1 to Day 393 ]
• Number of Participants that Contract Mild, Moderate, Severe and Moderate to Severe COVID-19 [ Time Frame: Day 1 to Day 393 ]
• Number of Participants Seroconverting to the Nucleocapsid (N) Protein of SARS-SoV-2 [ Time Frame: Day 1, 43, 211 and 393 ]
  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 prior to vaccination on Day 1 and Day 43.
• Burden of Disease (BoD) Score Based on First Episodes of Virologically-confirmed Cases of COVID-19 [ Time Frame: Day 1 to Day 393 ]
• Individual SARS-CoV-2 Neutralizing Antibody Levels in Serum [ Time Frame: Days 1, 29, 43, 57, 120, 211 and 393 ]
  Measured by a virus neutralizing assay in a subset of participants.
• Number of Participants Seroconverting to SARS-CoV-2 [ Time Frame: Days 1, 29, 43, 57, 120, 211 and 393 ]
  Measured by a virus neutralizing assay in a subset of participants.
• Individual Serum Antibodies to Spike (S) Protein of SARS-CoV-2 [ Time Frame: Days 43, 57, 120, 211 and 393 ]
  Measured by a virus neutralizing assay in a subset of participants.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study to Evaluate the Safety and Immunogenicity of Vaccine CVnCoV in Healthy Adults in Germany for COVID-19
• Official Title: COVID-19: A Phase 3, Randomized, Observer-Blinded, Placebo-Controlled Clinical Study Evaluating the Safety and Immunogenicity of Investigational SARS-CoV-2 mRNA Vaccine CVnCoV in Adult Health Care Workers in Mainz (Germany)
• Brief Summary: This study aims to evaluate the safety (in all participants) and reactogenicity (in a subset of participants) of CVnCoV administered as a 2-dose schedule to adult participants 18 years of age or older. The study also aims to assess antibody responses to the receptor-binding domain (RBD) of spike (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 participants.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Prevention

Condition

• Coronavirus
• Covid19
• SARS-CoV-2
• Severe Acute Respiratory Syndrome

Intervention

• Biological: CVnCoV Vaccine
  Intramuscular injection
  Other Name: CV07050101
• Drug: Placebo
  Intramuscular injection

Study Arms

• Experimental: CVnCoV: Group 1, Lot 1
  Participants in Group 1 will be vaccinated with CVnCoV 12 µg mRNA on Day 1 and Day 29 in the deltoid area, preferably in the non-dominant arm.
  Intervention: Biological: CVnCoV Vaccine
• Experimental: CVnCoV: Group 2, Lot 2
  Participants in Group 2 will be vaccinated with CVnCoV 12 µg mRNA on Day 1 and Day 29 in the deltoid area, preferably in the non-dominant arm.
  Intervention: Biological: CVnCoV Vaccine
• Placebo Comparator: Placebo
  Participants will receive a placebo on Day 1 and Day 29 in the deltoid area, preferably in the non-dominant arm.
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: February 8, 2022): 2351
• Original Estimated Enrollment (submitted: December 14, 2020): 2520
• Actual Study Completion Date: June 8, 2022
• Actual Primary Completion Date: June 8, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Male or female participants 18 years of age or older.
• Health care workers (HCWs), employees or students in clinical training.
• 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 urine pregnancy test (human chorionic gonadotropin 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 (IUDs);
  • Intrauterine hormone-releasing systems (IUSs);
  • Bilateral tubal ligation;
  • Vasectomized 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 SARS-CoV-2 infection or SARS-CoV-2 positive serology.
• For females: pregnancy or lactation.
• 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.
• Receipt of licensed vaccines within 28 days (for live vaccines) or 14 days (for inactivated vaccines) prior to the administration of trial vaccine.
• Prior administration of any investigational SARS-CoV-2 vaccine or other coronavirus (SARS-CoV, MERS-CoV) vaccine or planned use during the trial.
• Any treatment with immunosuppressants or other immune-modifying drugs (including but not limited to 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), 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.
• Active or chronic disease of, or currently on treatment for, hepatitis B virus (HBV) or hepatitis C virus (HCV).
• History of angioedema (hereditary or idiopathic), or a history of any anaphylactic reaction.
• History of Potential immune-mediated disease (pIMD).
• History of allergy to any component of CVnCoV vaccine.
• 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 un-controlled cardiovascular disease, gastrointestinal disease, liver disease, renal disease, respiratory disease, endocrine disorder, and neurological and psychiatric illnesses.
• Participants with impaired coagulation or any bleeding disorder in whom an intramuscular (IM) injection or a blood draw is contraindicated. However, those with controlled and stable cases can be included in the trial.
• Foreseeable non-compliance with protocol as judged by the Investigator.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Germany

Administrative Information

• NCT Number: NCT04674189
• Other Study ID Numbers: CV-NCOV-005
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: CureVac AG
• Original Responsible Party: Same as current
• Current Study Sponsor: CureVac AG
• Original Study Sponsor: Same as current
• Collaborators: German Federal Ministry of Education and Research
• Investigators: Not Provided
• PRS Account: CureVac AG
• Verification Date: February 2022