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
Overview
- Phase
- Phase 1
- Intervention
- CVnCoV Vaccine
- Conditions
- Severe Acute Respiratory Syndrome
- Sponsor
- CureVac
- Enrollment
- 280
- Locations
- 4
- Primary Endpoint
- 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
- Status
- Completed
- Last Updated
- 3 years ago
Overview
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.).
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
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.
Arms & Interventions
Dose Escalation CVnCoV
Participants will be vaccinated with CVnCoV at escalating dose levels on Day 1 and Day 29. Safety data will inform the decision to continue enrolling at the current dose level, or to proceed to dose escalation. Initially, dose levels of 2, 4 and 8 μg will be evaluated. Dose levels of 2, 4, 6, 8 and 12µg will be evaluated with potential increase to dose levels up to 20 μg.
Intervention: CVnCoV Vaccine
Dose Escalation Placebo
Participants will be given placebo on Day 1 and Day 29.
Intervention: Placebo
Outcomes
Primary Outcomes
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
Time Frame: Up to 60 hours after vaccination on Day 1
Grade 3 refers to the highest grading on the FDA toxicity scale where a higher grade indicates a worse outcome. An SAE was defined as any untoward medical occurrence that, at any dose: * Resulted in death. * Was life-threatening. * Required inpatient hospitalization or prolongation of existing hospitalization. * Resulted in persistent disability/incapacity. * Was a congenital anomaly/birth defect in the offspring of the participant. * Was an important medical event.
Number of Participants With Solicited Local Adverse Events
Time Frame: Up to 7 days after vaccination (Days 1 to 8 and Day 29 to 36)
Reactogenicity was assessed daily via collection of solicited local AEs (injection site pain, redness, swelling, and itching) using paper diary cards.
Intensity of Solicited Local Adverse Events Per the FDA Toxicity Grading Scale
Time Frame: Up to 7 days after vaccination (Days 1 to 8 and Days 29 to 36)
Reactogenicity was assessed daily via collection of solicited local AEs (injection site pain, redness, swelling, and itching) using paper diary cards. Intensity of solicited local AEs and solicited systemic AEs were graded per the FDA Toxicity Grading Scale at Grades 1-3, where higher grades indicate a worse outcome.
Duration of Solicited Local Adverse Events
Time Frame: Up to 7 days after vaccination (Days 1 to 8 and Days 29 to 36)
Reactogenicity was assessed daily via collection of solicited local AEs (injection site pain, redness, swelling, and itching) using paper diary cards. Duration was calculated as consecutive days with a respective solicited AE regardless of the grade of the AE.
Number of Participants With Solicited Systemic Adverse Events
Time Frame: Up to 7 days after vaccination (Days 1 to 8 and Days 29 to 36)
Reactogenicity was assessed daily via collection of solicited systemic AEs (fever, headache, fatigue, chills, myalgia, arthralgia, nausea/vomiting, and diarrhea) using paper diary cards.
Intensity of Solicited Systemic Adverse Events Per the FDA Toxicity Grading Scale
Time Frame: Up to 7 days after vaccination (Days 1 to 8 and Days 29 to 36)
Reactogenicity was assessed daily via collection of solicited systemic AEs (fever, headache, fatigue, chills, myalgia, arthralgia, nausea/vomiting, and diarrhea) using paper diary cards. Intensity of solicited local AEs and solicited systemic AEs were graded per the FDA Toxicity Grading Scale at Grades 1-3, where higher grades indicate a worse outcome.
Duration of Solicited Systemic Adverse Events
Time Frame: Up to 7 days after vaccination (Days 1 to 8 and Days 29 to 36)
Reactogenicity was assessed daily via collection of solicited systemic AEs (fever, headache, fatigue, chills, myalgia, arthralgia, nausea/vomiting, and diarrhea) using paper diary cards. Duration was calculated as consecutive days with a respective solicited AE regardless of the grade of the AE.
Number of Participants With Solicited Systemic Adverse Events Considered Related to Trial Vaccine
Time Frame: Up to 7 days after vaccination (Days 1 to 8 and Days 29 to 36)
Reactogenicity was assessed daily via collection of solicited systemic AEs (fever, headache, fatigue, chills, myalgia, arthralgia, nausea/vomiting, and diarrhea) using paper diary cards. The Investigator assessed the relationship between trial vaccine and each occurrence of each AE.
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
Time Frame: Up to 24 hours after vaccination on Day 1
Grade 3 refers to the highest grading on the FDA toxicity scale where a higher grade indicates a worse outcome. An SAE was defined as any untoward medical occurrence that, at any dose: * Resulted in death. * Was life-threatening. * Required inpatient hospitalization or prolongation of existing hospitalization. * Resulted in persistent disability/incapacity. * Was a congenital anomaly/birth defect in the offspring of the participant. * Was an important medical event.
Number of Participants With Unsolicited Adverse Events
Time Frame: Up to 28 days after vaccination (Days 1 to 29 and Days 29 to 57)
Diaries were used for collection of unsolicited AEs on each vaccination day and the following 28 days. In addition, participants were contacted by phone to verify whether they had any health concerns since the last visit.
Intensity of Unsolicited Adverse Events Assessed by the Investigator
Time Frame: Up to 28 days after vaccination (Days 1 to 29 and Days 29 to 57)
Diaries were used for collection of unsolicited AEs on each vaccination day and the following 28 days. In addition, participants were contacted by phone to verify whether they had any health concerns since the last visit. Participants were included only once, at the maximum severity. The Investigator made an assessment of intensity for each AE reported during the trial and assigned it to one of the following categories: * Mild: an event that was easily tolerated by the participant, causing minimal discomfort and not interfering with everyday activities. * Moderate: an event that caused sufficient discomfort to interfere with normal everyday activities. * Severe: an event that prevented normal everyday activities.
Number of Participants With Unsolicited Adverse Events Considered Related to Trial Vaccine
Time Frame: Up to 28 days after vaccination (Days 1 to 29 and Days 29 to 57)
Diaries were used for collection of unsolicited AEs on each vaccination day and the following 28 days. In addition, participants were contacted by phone to verify whether they had any health concerns since the last visit. The Investigator assessed the relationship between trial vaccine and each occurrence of each AE.
Number of Participants With One or More Serious Adverse Events (SAEs)
Time Frame: Baseline to Day 393
An SAE was defined as any untoward medical occurrence that, at any dose: * Resulted in death. * Was life-threatening. * Required inpatient hospitalization or prolongation of existing hospitalization. * Resulted in persistent disability/incapacity. * Was a congenital anomaly/birth defect in the offspring of the participant. * Was an important medical event.
Number of Participants With One or More Serious Adverse Events (SAEs) Considered Related to Trial Vaccine
Time Frame: Baseline to Day 393
An SAE was defined as any untoward medical occurrence that, at any dose: * Resulted in death. * Was life-threatening. * Required inpatient hospitalization or prolongation of existing hospitalization. * Resulted in persistent disability/incapacity. * Was a congenital anomaly/birth defect in the offspring of the participant. * Was an important medical event. The Investigator assessed the relationship between trial vaccine and each occurrence of each AE.
Number of Participants With One or More Adverse Events of Special Interest (AESIs)
Time Frame: Day 1 to Day 393
The following events will be considered as AESIs: adverse events with a suspected immune-mediated etiology, COVID-19 disease and other adverse events relevant to SARS-CoV vaccine development or the target disease.
Secondary Outcomes
- Number of Participants Seroconverting for SARS-CoV-2 Spike Protein Antibodies(Day 8, Day 15, Day 29, Day 36, Day 43, Day 57, Day 120 and Day 211)
- Geometric Mean Titers (GMTs) of Serum SARS-CoV-2 Spike Protein Antibodies(Day 8, Day 15, Day 29, Day 36, Day 43, Day 57, Day 120 and Day 211)
- Number of Participants Seroconverting for SARS-CoV-2 Spike Protein Receptor-Binding Domain (RBD) Antibodies(Day 8, Day 15, Day 29, Day 36, Day 43, Day 57, Day 120 and Day 211)
- Geometric Mean Titers (GMTs) of Serum SARS-CoV-2 Spike Protein Receptor-Binding Domain (RBD) Antibodies(Day 8, Day 15, Day 29, Day 36, Day 43, Day 57, Day 120 and Day 211)
- Number of Participants Seroconverting for SARS-CoV-2 Neutralizing Antibodies(Day 8, Day 15, Day 29, Day 36, Day 43, Day 57, Day 120 and Day 211)
- Geometric Mean Titers (GMTs) of Serum SARS-CoV-2 Neutralizing Antibodies(Day 8, Day 15, Day 29, Day 36, Day 43, Day 57, Day 120 and Day 211)