Clinical trial NCT04515147: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Coronavirus
Covid19
SARS-CoV-2
Severe Acute Respiratory Syndrome
Keywords: Vaccine
SARS
COVID
Safety
Reactogenicity
Immunogenicity
Lead sponsor: CureVac
Sponsor class: INDUSTRY
Collaborators: name: German Federal Ministry of Education and Research
First posted: 2020-08-17
Enrollment: 668
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: PREVENTION

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.).

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.

Primary outcomes:
measure: Number of Participants Who Experienced a Solicited Adverse Event (AE) Occurring on the Day of Vaccination and the Following 7 Days After Dose 1 and Dose 2
timeFrame: Up to 7 days after Dose 1 (Days 1 to 8) and Dose 2 (Days 29 to 36)
measure: Intensity of Solicited AEs Per US Food and Drug Administration (FDA) Toxicity Grading Scale Occurring on the Day of Vaccination and the Following 7 Days After Dose 1 and Dose 2
timeFrame: Up to 7 days after Dose 1 (Days 1 to 8) and Dose 2 (Days 29 to 36)
measure: Duration of Solicited AEs Occurring on the Day of Vaccination and the Following 7 Days After After Dose 1 and Dose 2
timeFrame: Up to 7 days after Dose 1 (Days 1 to 8) and Dose 2 (Days 29 to 36)
measure: Number of Participants Who Experienced an Unsolicited AE Occurring on the Day of Vaccination and the Following 28 Days After Dose 1 and Dose 2
timeFrame: Up to 28 days after Dose 1 (Days 1 to 29) and Dose 2 (Days 29 to 57)
measure: Intensity of Unsolicited AEs Per the Investigator's Assessment Occurring on the Day of Vaccination and the Following 28 Days After Dose 1 and Dose 2
timeFrame: Up to 28 days after Dose 1 (Days 1 to 29) and Dose 2 (Days 29 to 57)
measure: Number of Participants Who Experienced a Serious Adverse Event (SAE) During the Trial
timeFrame: Up to Day 393
measure: Number of Participants Who Experienced an Adverse Event of Special Interest (AESI) During the Trial
timeFrame: Up to Day 393
measure: Percentage of Participants Seroconverting for SARS-CoV-2 Spike Protein Receptor-Binding Domain (RBD) Antibodies on Day 29 and Day 43
timeFrame: Baseline, Day 29 and Day 43
measure: Geometric Mean Titers (GMTs) of SARS-CoV-2 Spike Protein RBD Antibodies on Day 29 and Day 43
timeFrame: Day 29 and Day 43
measure: Percentage of Participants Seroconverting for SARS-CoV-2 Neutralizing Antibodies on Day 29 and Day 43
timeFrame: Baseline, Day 29 and Day 43
measure: GMTs of SARS-CoV-2 Neutralizing Antibodies on Day 29 and Day 43
timeFrame: Day 29 and Day 43
Secondary outcomes:
measure: Number of Participants Who Experienced a Solicited Adverse Event (AE) Occurring on the Day of Booster Vaccination and the Following 7 Days
timeFrame: Up to 7 days after booster vaccination (Days 57 to 64 and Days 180 to 187)
measure: Intensity of Solicited AEs Per FDA Toxicity Grading Scale Occurring on the Day of Booster Vaccination and the Following 7 Days
timeFrame: Up to 7 days after booster vaccination (Days 57 to 64 and Days 180 to 187)
measure: Duration of Solicited AEs Occurring on the Day of Booster Vaccination and the Following 7 Days
timeFrame: Up to 7 days after booster vaccination (Days 57 to 64 and Days 180 to 187)
measure: Number of Participants Who Experienced an Unsolicited AE Occurring on the Day of Booster Vaccination and the Following 28 Days
timeFrame: Up to 28 days after booster vaccination (Days 57 to 85 and Days 180 to 208)
measure: Intensity of Unsolicited AEs Per the Investigator's Assessment Occurring on the Day of Booster Vaccination and the Following 28 Days
timeFrame: Up to 28 days after booster vaccination (Days 57 to 85 and Days 180 to 208)
measure: Percentage of Participants Seroconverting for SARS-CoV-2 Spike Protein RBD Antibodies on Day 57, Day 85, Day 180, Day 208 and Day 393
timeFrame: For participants who received the booster vaccination on Day 57: Baseline, Day 57, Day 85 and Day 180. For participants who received the booster vaccination on Day 180: Baseline, Day 180, Day 208 and Day 393
measure: GMTs of SARS-CoV-2 Spike Protein RBD Antibodies on Day 57, Day 85, Day 180, Day 208 and Day 393
timeFrame: For participants who received the booster vaccination on Day 57: Day 57, Day 85 and Day 180. For participants who received the booster vaccination on Day 180: Day 180, Day 208 and Day 393
measure: Percentage of Participants Seroconverting for SARS-CoV-2 Neutralizing Antibodies on Day 57, Day 85, Day 180, Day 208 and Day 393
timeFrame: For participants who received the booster vaccination on Day 57: Baseline, Day 57, Day 85 and Day 180. For participants who received the booster vaccination on Day 180: Baseline, Day 180, Day 208 and Day 393
measure: GMTs of SARS-CoV-2 Neutralizing Antibodies on Day 57, Day 85, Day 180, Day 208 and Day 393
timeFrame: For participants who received the booster vaccination on Day 57: Day 57, Day 85 and Day 180. For participants who received the booster vaccination on Day 180: Day 180, Day 208 and Day 393
Other outcomes:
Locations:
city: Panama city
country: Panama
facility: Centro de vacunación internacional - CEVAXIN Panama Clinic
city: Lima
country: Peru
facility: Instituto de Investigación Nutricional
Study officials:
References: