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

NCT04449276 | Completed Phase 1 Results DMC

• 2 other identifiers: CV-NCOV-0012020-001286-36
• Study Type: interventional
• Target: 280
• Locations: 2 countries
• Sites: 4

Brief Summary

This study aims to evaluate the safety and reactogenicity profile after 1 and 2 dose administrations of CVnCoV at different dose levels.

Conditions

Severe Acute Respiratory Syndrome; Coronavirus; SARS-CoV-2; COVID-19

Keywords

Safety; Reactogenicity; Immunogenicity; Vaccine; CEPI

Outcome Measures

Primary Outcomes (15)

• 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

  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.

  Up to 24 hours after vaccination on Day 1

• 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

  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.

  Up to 60 hours after vaccination on Day 1

• Number of Participants With Solicited Local Adverse Events

  Reactogenicity was assessed daily via collection of solicited local AEs (injection site pain, redness, swelling, and itching) using paper diary cards.

  Up to 7 days after vaccination (Days 1 to 8 and Day 29 to 36)

• Intensity of Solicited Local Adverse Events Per the FDA Toxicity Grading Scale

  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.

  Up to 7 days after vaccination (Days 1 to 8 and Days 29 to 36)

• Duration of Solicited Local Adverse Events

  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.

  Up to 7 days after vaccination (Days 1 to 8 and Days 29 to 36)

• Number of Participants With Solicited Systemic Adverse Events

  Reactogenicity was assessed daily via collection of solicited systemic AEs (fever, headache, fatigue, chills, myalgia, arthralgia, nausea/vomiting, and diarrhea) using paper diary cards.

  Up to 7 days after vaccination (Days 1 to 8 and Days 29 to 36)

• Intensity of Solicited Systemic Adverse Events Per the FDA Toxicity Grading Scale

  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.

  Up to 7 days after vaccination (Days 1 to 8 and Days 29 to 36)

• Duration of Solicited Systemic Adverse Events

  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.

  Up to 7 days after vaccination (Days 1 to 8 and Days 29 to 36)

• Number of Participants With Solicited Systemic Adverse Events Considered Related to Trial Vaccine

  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.

  Up to 7 days after vaccination (Days 1 to 8 and Days 29 to 36)

• Number of Participants With Unsolicited Adverse Events

  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.

  Up to 28 days after vaccination (Days 1 to 29 and Days 29 to 57)

• Intensity of Unsolicited Adverse Events Assessed by the Investigator

  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.

  Up to 28 days after vaccination (Days 1 to 29 and Days 29 to 57)

• Number of Participants With Unsolicited Adverse Events Considered Related to Trial Vaccine

  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.

  Up to 28 days after vaccination (Days 1 to 29 and Days 29 to 57)

• Number of Participants With One or More Serious Adverse Events (SAEs)

  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.

  Baseline to Day 393

• Number of Participants With One or More Serious Adverse Events (SAEs) Considered Related to Trial Vaccine

  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.

  Baseline to Day 393

• Number of Participants With One or More Adverse Events of Special Interest (AESIs)

  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.

  Day 1 to Day 393

Secondary Outcomes (6)

• 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

Study Arms (2)

Dose Escalation CVnCoV

EXPERIMENTAL

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.

Biological: CVnCoV Vaccine

Dose Escalation Placebo

PLACEBO COMPARATOR

Participants will be given placebo on Day 1 and Day 29.

Drug: Placebo

Interventions

CVnCoV Vaccine BIOLOGICAL

Participants will receive an intramuscular injection by needle in the deltoid area.

Also known as: CV07050101

Dose Escalation CVnCoV

Placebo DRUG

Participants will receive an intramuscular injection by needle in the deltoid area.

Dose Escalation Placebo

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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).

You may not qualify if:

• 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 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.
• 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.

Sponsors & Collaborators

• CureVac: lead
• Coalition for Epidemic Preparedness Innovations: collaborator

Study Sites (4)

Universitair Ziekenhuis Ghent

Ghent, 9000, Belgium

Location

Ludwig-Maximilians-Universität München

München, Bavaria, 80802, Germany

Location

Medical University Hannover (MHH)

Hanover, 30625, Germany

Location

University Hospital Tübingen Institut für Tropenmedizin

Tübingen, 72074, Germany

Location

MeSH Terms

Conditions

Severe Acute Respiratory Syndrome; Coronavirus Infections; COVID-19

Interventions

CVnCoV COVID-19 vaccine

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases

Results Point of Contact

• Title: Clinical Trial Information
• Organization: CureVac AG

clinicaltrials@curevac.com

+49 6976805870

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: In the initial part of the dose escalation, participants will be enrolled in sentinel groups in an open manner. In the second part, participants will be enrolled in placebo-controlled groups in an observer-blind manner.
• Purpose: PREVENTION
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 18, 2020
• First Posted: June 26, 2020
• Study Start: June 18, 2020
• Primary Completion: December 21, 2021
• Study Completion: December 21, 2021
• Last Updated: January 30, 2023
• Results First Posted: January 30, 2023

Record last verified: 2022-04

Locations

DE (3); BE (1)