A Dose-Confirmation Study to Evaluate the Safety, Reactogenicity and Immunogenicity of Vaccine CVnCoV in Healthy Adults for COVID-19

• ClinicalTrials.gov Identifier: NCT04515147
• Recruitment Status: Completed
• First Posted: August 17, 2020
• Last Update Posted: March 24, 2022
• Sponsor: CureVac AG
• Collaborator: German Federal Ministry of Education and Research
• Information provided by (Responsible Party): CureVac AG

Tracking Information

• First Submitted Date: August 13, 2020
• First Posted Date: August 17, 2020
• Last Update Posted Date: March 24, 2022
• Actual Study Start Date: September 28, 2020
• Actual Primary Completion Date: February 21, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 13, 2020)

• 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 Solicited Systemic Adverse Events Considered Related to Trial Vaccine [ 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 FDA Toxicity Grading Scale [ Time Frame: 28 days after vaccination ]
• Number of Participants with Unsolicited Adverse Events Considered Related to Trial Vaccine [ Time Frame: 28 days after vaccination ]
• Number of Participants with One or More Serious Adverse Events (SAEs) [ Time Frame: Baseline to Day 393 ]
• Number of Participants with One or More Serious Adverse Events (SAEs) Considered Related to Trial Vaccine [ Time Frame: Baseline to Day 393 ]
• Number of Participants with One or More Adverse Events of Special Interest (AESIs) [ Time Frame: Baseline to Day 393 ]
• Number of Participants with One or More Adverse Events of Special Interest (AESIs) Considered Related to Trial Vaccine [ Time Frame: Baseline to Day 393 ]
• Number of Participants Seroconverting for SARS-CoV-2 Spike Protein Antibodies [ Time Frame: Day 29 ]
  Measured using Enzyme-Linked Immunosorbent Assay (ELISA).
• Number of Participants Seroconverting for SARS-CoV-2 Spike Protein Antibodies [ Time Frame: Day 43 ]
  Measured using Enzyme-Linked Immunosorbent Assay (ELISA).
• Individual SARS-CoV-2 Spike Protein-Specific Antibody Levels in Serum [ Time Frame: Day 29 ]
  Measured using Enzyme-Linked Immunosorbent Assay (ELISA).
• Individual SARS-CoV-2 Spike Protein-Specific Antibody Levels in Serum [ Time Frame: Day 43 ]
  Measured using Enzyme-Linked Immunosorbent Assay (ELISA).
• Geometric Mean Titers (GMTs) of Serum SARS-CoV-2 Spike Protein Antibodies [ Time Frame: Day 29 ]
  Measured using Enzyme-Linked Immunosorbent Assay (ELISA).
• Geometric Mean Titers (GMTs) of Serum SARS-CoV-2 Spike Protein Antibodies [ Time Frame: Day 43 ]
  Measured using Enzyme-Linked Immunosorbent Assay (ELISA).
• Number of Participants Seroconverting for SARS-CoV-2 Neutralizing Antibodies [ Time Frame: Day 29 ]
  Measured using an activity assay.
• Number of Participants Seroconverting for SARS-CoV-2 Neutralizing Antibodies [ Time Frame: Day 43 ]
  Measured using an activity assay.
• Individual SARS-CoV-2 Neutralizing Antibody Levels in Serum [ Time Frame: Day 29 ]
  Measured using an activity assay.
• Individual SARS-CoV-2 Neutralizing Antibody Levels in Serum [ Time Frame: Day 43 ]
  Measured using an activity assay.
• Geometric Mean Titers (GMTs) of Serum SARS-CoV-2 Neutralizing Antibodies [ Time Frame: Day 29 ]
  Measured using an activity assay.
• Geometric Mean Titers (GMTs) of Serum SARS-CoV-2 Neutralizing Antibodies [ Time Frame: Day 43 ]
  Measured using an activity assay.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: August 23, 2021)

• Number of Participants with Solicited Local Adverse Events Following the Booster Vaccine [ Time Frame: 7 days after booster vaccination ]
  During Part 1, booster vaccinations will be administered to participants in Group 3 and a sub-group of participants in Group 4.
• Intensity of Solicited Local Adverse Events per the FDA Toxicity Grading Scale Following the Booster Vaccine [ Time Frame: 7 days after booster vaccination ]
  During Part 1, booster vaccinations will be administered to participants in Group 3 and a sub-group of participants in Group 4.
• Duration of Solicited Local Adverse Events Following the Booster Vaccine [ Time Frame: 7 days after booster vaccination ]
  During Part 1, booster vaccinations will be administered to participants in Group 3 and a sub-group of participants in Group 4.
• Number of Participants with Solicited Systemic Adverse Events Following the Booster Vaccine [ Time Frame: 7 days after booster vaccination ]
  During Part 1, booster vaccinations will be administered to participants in Group 3 and a sub-group of participants in Group 4.
• Intensity of Solicited Systemic Adverse Events per the FDA Toxicity Grading Scale Following the Booster Vaccine [ Time Frame: 7 days after booster vaccination ]
  During Part 1, booster vaccinations will be administered to participants in Group 3 and a sub-group of participants in Group 4.
• Duration of Solicited Systemic Adverse Events Following the Booster Vaccine [ Time Frame: 7 days after booster vaccination ]
  During Part 1, booster vaccinations will be administered to participants in Group 3 and a sub-group of participants in Group 4.
• Number of Participants with Solicited Systemic Adverse Events Considered Related to Trial Vaccine Following the Booster Vaccine [ Time Frame: 7 days after booster vaccination ]
  During Part 1, booster vaccinations will be administered to participants in Group 3 and a sub-group of participants in Group 4.
• Number of Participants with Unsolicited Adverse Events Following the Booster Vaccine [ Time Frame: 28 days after booster vaccination ]
  During Part 1, booster vaccinations will be administered to participants in Group 3 and a sub-group of participants in Group 4.
• Intensity of Unsolicited Adverse Events per the FDA Toxicity Grading Scale Following the Booster Vaccine [ Time Frame: 28 days after booster vaccination ]
  During Part 1, booster vaccinations will be administered to participants in Group 3 and a sub-group of participants in Group 4.
• Number of Participants with Unsolicited Adverse Events Considered Related to Trial Vaccine Following the Booster Vaccine [ Time Frame: 28 days after booster vaccination ]
  During Part 1, booster vaccinations will be administered to participants in Group 3 and a sub-group of participants in Group 4.
• Number of Participants Seroconverting for SARS-CoV-2 Spike Protein Antibodies [ Time Frame: Day 57, Day 85, Day 180, Day 208 and Day 393 ]
  Measured using Enzyme-Linked Immunosorbent Assay (ELISA).
• Individual SARS-CoV-2 Spike Protein-Specific Antibody Levels in Serum [ Time Frame: Day 57, Day 85, Day 180, Day 208 and Day 393 ]
  Measured using Enzyme-Linked Immunosorbent Assay (ELISA).
• Geometric Mean Titers (GMTs) of Serum SARS-CoV-2 Spike Protein Antibodies [ Time Frame: Day 57, Day 85, Day 180, Day 208 and Day 393 ]
  Measured using Enzyme-Linked Immunosorbent Assay (ELISA).
• Number of Participants Seroconverting for SARS-CoV-2 Neutralizing Antibodies [ Time Frame: Day 57, Day 85, Day 180, Day 208 and Day 393 ]
  Measured using an activity assay.
• Individual SARS-CoV-2 Neutralizing Antibody Levels in Serum [ Time Frame: Day 57, Day 85, Day 180, Day 208 and Day 393 ]
  Measured using an activity assay.
• Geometric Mean Titers (GMTs) of Serum SARS-CoV-2 Neutralizing Antibodies [ Time Frame: Day 57, Day 85, Day 180, Day 208 and Day 393 ]
  Measured using an activity assay.
• 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 in all age Groups [ Time Frame: 15 days after second vaccination ]
• 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 per age Group [ Time Frame: 15 days after second vaccination ]
• 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 in all age Groups [ Time Frame: Day 1 up 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 per age Group [ Time Frame: Day 1 up to Day 393 ]

Original Secondary Outcome Measures (submitted: August 13, 2020)

• Number of Participants Seroconverting for SARS-CoV-2 Spike Protein Antibodies [ Time Frame: Day 180, Day 208 and Day 393 ]
  Measured using Enzyme-Linked Immunosorbent Assay (ELISA).
• Individual SARS-CoV-2 Spike Protein-Specific Antibody Levels in Serum [ Time Frame: Day 180, Day 208 and Day 393 ]
  Measured using Enzyme-Linked Immunosorbent Assay (ELISA).
• Geometric Mean Titers (GMTs) of Serum SARS-CoV-2 Spike Protein Antibodies [ Time Frame: Day 180, Day 208 and Day 393 ]
  Measured using Enzyme-Linked Immunosorbent Assay (ELISA).
• Number of Participants Seroconverting for SARS-CoV-2 Neutralizing Antibodies [ Time Frame: Day 180, Day 208 and Day 393 ]
  Measured using an activity assay.
• Individual SARS-CoV-2 Neutralizing Antibody Levels in Serum [ Time Frame: Day 180, Day 208 and Day 393 ]
  Measured using an activity assay.
• Geometric Mean Titers (GMTs) of Serum SARS-CoV-2 Neutralizing Antibodies [ Time Frame: Day 180, Day 208 and Day 393 ]
  Measured using an activity assay.

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

Descriptive Information

• Brief Title: A Dose-Confirmation Study to Evaluate the Safety, Reactogenicity and Immunogenicity of Vaccine CVnCoV in Healthy Adults for COVID-19
• Official Title: COVID-19: A Phase 2a, Partially Observer-blind, Multicenter, Controlled, Dose-confirmation Clinical Trial to Evaluate the Safety, Reactogenicity and Immunogenicity of the Investigational SARS-CoV-2 mRNA Vaccine CVnCoV in Adults >60 Years of Age and 18 to 60 Years of Age
• Brief Summary: This study aims to evaluate the safety and reactogenicity profile after 1 and 2 dose administrations of investigational SARS-CoV-2 mRNA vaccine (CVnCoV) at different dose levels and to evaluate the humoral immune response after 1 and 2 dose administrations of CVnCoV.
• Detailed Description: 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.).
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Sequential Assignment; Masking: Triple (Participant, Investigator, Outcomes Assessor); Primary Purpose: Prevention

Condition

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

Intervention

• Biological: CVnCoV 6 μg
  Participants will receive an intramuscular injection by needle in the deltoid area.
  Other Name: CV07050101
• Biological: CVnCoV 12 μg
  Participants will receive an intramuscular injection by needle in the deltoid area.
  Other Name: CV07050101
• Biological: Hepatitis A vaccine
  Participants will receive an intramuscular injection by needle in the deltoid area.
• Biological: Pneumococcal vaccine
  Participants will receive an intramuscular injection by needle in the deltoid area.
• Biological: CVnCoV 12μg
  Participants will receive an intramuscular injection by needle in the deltoid area.
  Other Name: CV07050101

Study Arms

• Experimental: Part 1, Group 1: CVnCoV 6 μg
  Participants will be vaccinated with CVnCoV on Day 1 and Day 29. Participants in this group will be aged between 18 and 60 years old.
  Intervention: Biological: CVnCoV 6 μg
• Experimental: Part 1, Group 2: CVnCoV 6 μg
  Participants will be vaccinated with CVnCoV on Day 1 and Day 29. Participants in this group will be aged over 60 years old.
  Intervention: Biological: CVnCoV 6 μg
• Experimental: Part 1, Group 3: CVnCoV 12 μg

  Participants will be vaccinated with CVnCoV on Day 1 and Day 29. Participants in this group will be between the ages of 18 to 60 years old.

  CVnCoV will be administered again as a booster vaccination on Day 180 in a sub-group of participants.

  Intervention: Biological: CVnCoV 12 μg
• Experimental: Part 1, Group 4: CVnCoV 12 μg

  Participants will be vaccinated with CVnCoV on Day 1 and Day 29. Participants in this group will be aged over 60 years old.

  CVnCoV will be administered again as a booster vaccination on Day 57 or Day 180 in a sub-group of participants.

  Intervention: Biological: CVnCoV 12 μg
• Active Comparator: Part 1, Group 5: Hepatitis A vaccine
  Participants will be vaccinated with a hepatitis A vaccine on Day 1 and Day 29. Participants in this group will be aged between 18 and 60 years old.
  Intervention: Biological: Hepatitis A vaccine
• Active Comparator: Part 1, Group 6: Pneumococcal vaccine
  Participants will be vaccinated with a pneumococcal vaccine on Day 1 and Day 29. Participants in this group will be aged over 60 years old.
  Intervention: Biological: Pneumococcal vaccine
• Experimental: Part 2, Group 1: CVnCoV 12 µg
  Participants will be vaccinated with CVnCoV 12 µg on Day 1 and Day 29. Participants in this group will be aged between 18 and 60 years old.
  Intervention: Biological: CVnCoV 12μg
• Active Comparator: Part 2, Group 2: Hepatitis A vaccine
  Participants will be vaccinated with a hepatitis A vaccine on Day 1 and Day 29. Participants in this group will be aged between 18 and 60 years old.
  Intervention: Biological: Hepatitis A vaccine
• Experimental: Part 2, Group 3: CVnCoV 12 µg
  Participants will be vaccinated with CVnCoV 12 µg on Day 1 and Day 29. Participants in this group will be aged over 60 years old.
  Intervention: Biological: CVnCoV 12μg
• Active Comparator: Part 2, Group 4: Pneumococcal vaccine
  Participants will be vaccinated with a pneumococcal vaccine on Day 1 and Day 29. Participants in this group will be aged over 60 years old.
  Intervention: Biological: Pneumococcal vaccine

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: January 11, 2021): 674
• Original Estimated Enrollment (submitted: August 13, 2020): 691
• Actual Study Completion Date: February 21, 2022
• Actual Primary Completion Date: February 21, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Healthy male and female participants ≥18 years of age. A healthy participant is defined as an individual who is in good general health, according to the Investigator's assessment. Chronic health conditions are acceptable if the condition is considered well controlled with treatment according to the discretion of the Investigator.
• Expected to be compliant with protocol procedures and available for clinical follow-up through the last planned visit.
• Participants are able to understand and willing to provide informed consent.
• Physical examination without clinically significant findings according to the Investigator's assessment.
• Body mass index (BMI) ≥18.0 and ≤32.0 kg/m^2.
• Female participants of childbearing potential: at the time of enrollment, negative human chorionic gonadotropin (hCG) pregnancy test (serum) for female participants presumed to be of childbearing potential on the day of enrollment. On Day 1 (pre-vaccination): negative urine pregnancy test (required if serum pregnancy test was performed more than 3 days before).

• 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. 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 occlusion;
  • Vasectomized partner;
  • Sexual abstinence (periodic abstinence [e.g., calendar, ovulation, symptothermal and post-ovulation methods] and withdrawal are not acceptable).
• Male participants should be instructed not to get their partners pregnant until 3 months after the last administration.

Exclusion Criteria:

• 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.
• 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 (primary dose or booster dose).
• Receipt of any investigational or licensed/authorized SARS-CoV-2 or other coronavirus vaccine prior to the administration of the trial vaccine.
• Any treatment with immunosuppressants or other immune-modifying drugs (including, but not limited to, corticosteroids, biologicals, and methotrexate) within 6 months prior to the administration of the trial vaccine or planned use during the trial, with the exception of topically-applied, inhaled, or intranasal steroids.
• Use of hormonal therapy for gender reassignment.
• Any medically diagnosed or suspected immunosuppressive or immunodeficient condition based on medical history and physical examination, including known human immunodeficiency virus infection, hepatitis B virus infection, and hepatitis C virus infection.
• History of immune-mediated or autoimmune disease.
• History of angioedema (known C1 inhibitor deficiency).
• History of anaphylaxis or allergy to any component of CVnCoV or aminoglycoside antibiotics.
• History of or current alcohol and/or drug abuse.
• Participants who are active smokers, were active smokers within the last year (including any vaping in the last year), or have a total smoking history ≥10 pack years. A pack year is calculated by multiplying the number of packs of cigarettes smoked per day by the number of years the person has smoked.
• History of virologically-confirmed Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS), or COVID-19 disease or known exposure (without any personal protective equipment) to an individual with confirmed COVID-19 disease or SARS-CoV-2 infection within the past 2 weeks.
• Administration of immunoglobulins and/or any blood products within the 3 months preceding the administration of any dose of the trial vaccine.

• Presence or evidence of significant uncontrolled acute or chronic medical or psychiatric illness. Significant medical or psychiatric illnesses include but are not limited to:

  • Uncontrolled respiratory disease (e.g., chronic obstructive pulmonary disease, asthma), including use of the following asthma medications: intravenous corticosteroids, leukotriene modifiers, biologics.
  • Uncontrolled cardiovascular disease (e.g., congestive heart failure, cardiomyopathy, ischemic heart disease, history of stroke, peripheral artery disease, pulmonary embolism).
  • History of myocarditis or pericarditis as an adult.
  • Diabetes mellitus (insulin-dependent).
  • 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.
• Foreseeable non-compliance with protocol, as judged by the Investigator.
• For female participants: pregnancy or lactation.
• Participants with impaired coagulation or any bleeding disorder in whom an intramuscular 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.
• Participants employed by the Sponsor, Investigator, or trial site, or relatives of research staff working on this trial.
• Participants considered at the Investigator's discretion to be at increased risk of exposure to COVID-19 disease.

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: Panama, Peru

Administrative Information

• NCT Number: NCT04515147
• Other Study ID Numbers: CV-NCOV-002
• 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
• Responsible Party: CureVac AG
• Study Sponsor: CureVac AG
• Collaborators: German Federal Ministry of Education and Research
• Investigators: Not Provided
• PRS Account: CureVac AG
• Verification Date: December 2021