Clinical trial NCT04449276: A Study to Evaluate the Safety, Reactogenicity and Immunogenicity of Vaccine CVnCoV in Healthy Adults for COVID-19
Official title: COVID-19: A Phase 1, Partially Blind, Placebo-controlled, Dose Escalation, First-in-human, Clinical Trial to Evaluate the Safety, Reactogenicity and Immunogenicity After 1 and 2 Doses of the Investigational SARS-CoV-2 mRNA Vaccine CVnCoV Administered Intramuscularly in Healthy Adults
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Severe Acute Respiratory Syndrome
Coronavirus
SARS-CoV-2
COVID-19
Keywords: Safety
Reactogenicity
Immunogenicity
Vaccine
CEPI
Lead sponsor: CureVac
Sponsor class: INDUSTRY
Collaborators: name: Coalition for Epidemic Preparedness Innovations
First posted: 2020-06-26
Enrollment: 280
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: 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 CVnCoV at different dose levels.

Detailed description: Funded by Coalition for Epidemic Preparedness Innovations (CEPI).

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 for all participants:

* Healthy male and female participants aged 18 to 60 years inclusive. Healthy participant is defined as an individual who is in good general health, not having any mental or physical disorder requiring regular or frequent medication.
* Expected to be compliant with protocol procedures and available for clinical follow-up through the last planned visit.
* Physical examination and laboratory results without clinically significant findings according to the Investigator's assessment.
* Body Mass Index (BMI) ≥18.0 and ≤30.0kg/m\^2 (≥18.0 and ≤32.0kg/m2 for participants with SARS-CoV-2 positive serology).
* Females: 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 the serum pregnancy test was performed more than 3 days before).
* Females of childbearing potential must use highly effective methods of birth control from 1 month 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 occlusion;
  * Vasectomized partner;
  * Sexual abstinence (periodic abstinence \[e.g., calendar, ovulation, symptothermal and post-ovulation methods\] and withdrawal are not acceptable).

Exclusion Criteria:

The following criterion applies to all open-label sentinel participants:

* Participants with SARS-CoV-2 positive serology as confirmed by testing at enrollment.

The following criteria apply to all participants, except those with SARS-CoV-2 positive serology:

* Participants considered at the Investigator's discretion to be at increased risk to acquire COVID-19 disease (including, but not limited to, health care workers with direct involvement in patient care or care of long-term care recipients).
* History of confirmed COVID-19 disease or known exposure to an individual with confirmed COVID-19 disease or SARS-CoV-2 infection within the past 2 weeks.

The following criteria apply to all participants:

* 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 14 days (for inactivated vaccines) or 28 days (for live vaccines) prior to enrollment in this trial or planned receipt of any vaccine within 28 days of trial vaccine administration.
* Receipt of any investigational SARS-CoV-2 or other CoV vaccine prior to the administration of the trial vaccine.
* Any treatment with immunosuppressants or other immune-modifying drugs within 6 months prior to the administration of the trial vaccine or planned use during the trial, with the exception of topically-applied steroids. Corticosteroids used in the context of COVID-19 disease of participants with SARS CoV 2 positive serology are not exclusionary.
* 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 a pIMD (potential immune-mediated disease).
* History of angioedema.
* Any known allergy, including allergy to any component of CVnCoV or aminoglycoside antibiotics. A history of hay fever or seasonal allergies (pollinosis) that does not require current treatment (e.g., anti-histamines) during the vaccination period (1 month before first vaccination until 1 month after last vaccination) is not exclusionary.
* 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.
* Active or currently active SARS-CoV-2 infection as confirmed by reactive PCR within 3 days of first trial vaccine administration.
* History of confirmed SARS or MERS
* Administration of immunoglobulins (Igs) and/or any blood products within the 3 months preceding the administration of any dose of the trial vaccine.
* Presence or evidence of significant acute or chronic, medical or psychiatric illness. Significant medical or psychiatric illnesses include but are not limited to:

  * Respiratory disease (e.g., chronic obstructive pulmonary disease \[COPD\], asthma) requiring daily medications currently or any treatment of respiratory disease exacerbations (e.g., asthma exacerbation) in the last 5 years.
  * Respiratory disease with clinically significant dyspnea in the last 5 years (except COVID-19 disease in participants with SARS-CoV-2 positive serology).
  * Asthma medications: inhaled, oral, or intravenous (IV) corticosteroids, leukotriene modifiers, long- and short-acting beta agonists, theophylline, ipratropium, biologics.
  * Significant cardiovascular disease (e.g., congestive heart failure, cardiomyopathy, ischemic heart disease, history of stroke, peripheral artery disease, pulmonary embolism) or history of myocarditis or pericarditis as an adult.
  * Elevated blood pressure or hypertension, even if well-controlled.
  * Diabetes mellitus type 1 or 2.
  * History of any neurological disorders or seizures including Guillain-Barré syndrome, with the exception of 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 females: pregnancy or lactation.
* History of any anaphylactic reactions.
* Participants with impaired coagulation or any bleeding disorder in whom an IM injection or a blood draw is contraindicated.
* Participants employed by the Sponsor, Investigator or trial site, or relatives of research staff working on this trial.

Primary outcomes:
measure: Number of Participants With Grade 3 Adverse Reactions or Any Serious Adverse Event (SAE) Considered Related to Trial Vaccine Within at Least 24 Hours After the First Vaccination
timeFrame: Up to 24 hours after vaccination on Day 1
measure: Number of Participants With Grade 3 Adverse Reactions or Any Serious Adverse Event (SAE) Considered Related to Trial Vaccine Within at Least 60 Hours After the First Vaccination
timeFrame: Up to 60 hours after vaccination on Day 1
measure: Number of Participants With Solicited Local Adverse Events
timeFrame: Up to 7 days after vaccination (Days 1 to 8 and Day 29 to 36)
measure: Intensity of Solicited Local Adverse Events Per the FDA Toxicity Grading Scale
timeFrame: Up to 7 days after vaccination (Days 1 to 8 and Days 29 to 36)
measure: Duration of Solicited Local Adverse Events
timeFrame: Up to 7 days after vaccination (Days 1 to 8 and Days 29 to 36)
measure: Number of Participants With Solicited Systemic Adverse Events
timeFrame: Up to 7 days after vaccination (Days 1 to 8 and Days 29 to 36)
measure: Intensity of Solicited Systemic Adverse Events Per the FDA Toxicity Grading Scale
timeFrame: Up to 7 days after vaccination (Days 1 to 8 and Days 29 to 36)
measure: Duration of Solicited Systemic Adverse Events
timeFrame: Up to 7 days after vaccination (Days 1 to 8 and Days 29 to 36)
measure: Number of Participants With Solicited Systemic Adverse Events Considered Related to Trial Vaccine
timeFrame: Up to 7 days after vaccination (Days 1 to 8 and Days 29 to 36)
measure: Number of Participants With Unsolicited Adverse Events
timeFrame: Up to 28 days after vaccination (Days 1 to 29 and Days 29 to 57)
measure: Intensity of Unsolicited Adverse Events Assessed by the Investigator
timeFrame: Up to 28 days after vaccination (Days 1 to 29 and Days 29 to 57)
measure: Number of Participants With Unsolicited Adverse Events Considered Related to Trial Vaccine
timeFrame: Up to 28 days after vaccination (Days 1 to 29 and Days 29 to 57)
measure: Number of Participants With One or More Serious Adverse Events (SAEs)
timeFrame: Baseline to Day 393
measure: Number of Participants With One or More Serious Adverse Events (SAEs) Considered Related to Trial Vaccine
timeFrame: Baseline to Day 393
measure: Number of Participants With One or More Adverse Events of Special Interest (AESIs)
timeFrame: Day 1 to Day 393
Secondary outcomes:
measure: Number of Participants Seroconverting for SARS-CoV-2 Spike Protein Antibodies
timeFrame: Day 8, Day 15, Day 29, Day 36, Day 43, Day 57, Day 120 and Day 211
measure: Geometric Mean Titers (GMTs) of Serum SARS-CoV-2 Spike Protein Antibodies
timeFrame: Day 8, Day 15, Day 29, Day 36, Day 43, Day 57, Day 120 and Day 211
measure: Number of Participants Seroconverting for SARS-CoV-2 Spike Protein Receptor-Binding Domain (RBD) Antibodies
timeFrame: Day 8, Day 15, Day 29, Day 36, Day 43, Day 57, Day 120 and Day 211
measure: Geometric Mean Titers (GMTs) of Serum SARS-CoV-2 Spike Protein Receptor-Binding Domain (RBD) Antibodies
timeFrame: Day 8, Day 15, Day 29, Day 36, Day 43, Day 57, Day 120 and Day 211
measure: Number of Participants Seroconverting for SARS-CoV-2 Neutralizing Antibodies
timeFrame: Day 8, Day 15, Day 29, Day 36, Day 43, Day 57, Day 120 and Day 211
measure: Geometric Mean Titers (GMTs) of Serum SARS-CoV-2 Neutralizing Antibodies
timeFrame: Day 8, Day 15, Day 29, Day 36, Day 43, Day 57, Day 120 and Day 211
Other outcomes:
Locations:
city: Ghent
country: Belgium
facility: Universitair Ziekenhuis Ghent
city: München
country: Germany
facility: Ludwig-Maximilians-Universität München
state: Bavaria
city: Hannover
country: Germany
facility: Medical University Hannover (MHH)
city: Tübingen
country: Germany
facility: University Hospital Tübingen Institut für Tropenmedizin
Study officials:
References: