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

NCT04515147 | Completed Phase 2 Results DMC

• 1 other identifier: CV-NCOV-002
• Study Type: interventional
• Target: 668
• Locations: 2 countries
• Sites: 2

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.

Conditions

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

Keywords

Vaccine; SARS; COVID; Safety; Reactogenicity; Immunogenicity

Outcome Measures

Primary Outcomes (11)

• 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

  Solicited local AEs (injection site pain, redness, swelling, and itching) and solicited systemic AEs (fever, headache, fatigue, chills, myalgia, arthralgia, nausea/vomiting, and diarrhea) were recorded on the day of vaccination and the following 7 days using a diary (electronic or paper). By definition, all solicited local AEs occurring from the time of first vaccination were considered related to trial vaccination. For solicited systemic AEs, the Investigator assessed the relationship between trial vaccine and each occurrence of each AE.

  Up to 7 days after Dose 1 (Days 1 to 8) and Dose 2 (Days 29 to 36)

• 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

  Solicited local AEs (injection site pain, redness, swelling, and itching) and solicited systemic AEs (fever, headache, fatigue, chills, myalgia, arthralgia, nausea/vomiting, and diarrhea) were recorded on the day of vaccination and the following 7 days using a diary (electronic or paper). 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 Dose 1 (Days 1 to 8) and Dose 2 (Days 29 to 36)

• Duration of Solicited AEs Occurring on the Day of Vaccination and the Following 7 Days After After Dose 1 and Dose 2

  Solicited local AEs (injection site pain, redness, swelling, and itching) and solicited systemic AEs (fever, headache, fatigue, chills, myalgia, arthralgia, nausea/vomiting, and diarrhea) were recorded on the day of vaccination and the following 7 days using a diary (electronic or paper). Duration is calculated as consecutive days with a respective solicited AE regardless of the grade of the AE. AEs ongoing after day 8 are included.

  Up to 7 days after Dose 1 (Days 1 to 8) and Dose 2 (Days 29 to 36)

• 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

  Diaries were used for collection of unsolicited AEs on each vaccination day and the following 28 days. In addition, participants received a prompt (by e.g., a phone call or text message) to verify whether the participants 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 Dose 1 (Days 1 to 29) and Dose 2 (Days 29 to 57)

• 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

  Diaries were used for collection of unsolicited AEs on each vaccination day and the following 28 days. In addition, participants received a prompt (by e.g., a phone call or text message) to verify whether the participants had any health concerns since the last visit. 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 Dose 1 (Days 1 to 29) and Dose 2 (Days 29 to 57)

• Number of Participants Who Experienced a Serious Adverse Event (SAE) During the Trial

  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.

  Up to Day 393

• Number of Participants Who Experienced an Adverse Event of Special Interest (AESI) During the Trial

  AESIs included: * AEs with a suspected immune-medicated etiology. * COVID-19 disease. * Other AEs relevant to SARS-CoV-2 vaccine development or the target disease. Participants who became unblinded and/or received a licensed/authorized vaccine were censored at the day after unblinding or at the day after receiving the licensed/authorized vaccine, whichever was earlier. The Investigator assessed the relationship between trial vaccine and each occurrence of each AE.

  Up to Day 393

• Percentage of Participants Seroconverting for SARS-CoV-2 Spike Protein Receptor-Binding Domain (RBD) Antibodies on Day 29 and Day 43

  As measured by enzyme-linked immunosorbent assay (ELISA). In participants not exposed to SARS-CoV-2 before the trial seroconversion was defined as any increase in titer in antibodies against SARS-CoV-2 RBD versus baseline. Participants who received a licensed/authorized vaccine were censored at the day after receiving the licensed/authorized vaccine.

  Baseline, Day 29 and Day 43

• Geometric Mean Titers (GMTs) of SARS-CoV-2 Spike Protein RBD Antibodies on Day 29 and Day 43

  As measured by ELISA. The SARS-CoV-2 spike RBD protein-specific antibodies are expressed as GMT (geometric mean of reciprocal duplicate dilutions). Concentration/titers marked as below the lower limit of quantification (LLOQ) were arbitrary replaced by half of the LLOQ for GMT computations purpose. Participants who received a licensed/authorized vaccine were censored at the day after receiving the licensed/authorized vaccine.

  Day 29 and Day 43

• Percentage of Participants Seroconverting for SARS-CoV-2 Neutralizing Antibodies on Day 29 and Day 43

  As measured by an activity assay. In participants not exposed to SARS-CoV-2 before the trial, seroconversion was defined as any increase in titer in SARS-CoV-2 neutralizing antibodies versus baseline. Participants who received a licensed/authorized vaccine were censored at the day after receiving the licensed/ authorized vaccine.

  Baseline, Day 29 and Day 43

• GMTs of SARS-CoV-2 Neutralizing Antibodies on Day 29 and Day 43

  The SARS-CoV-2 neutralizing antibodies are expressed as GMT (geometric mean of reciprocal duplicate dilutions). Concentration/titers marked as below the lower limit of quantification (LLOQ) were arbitrary replaced by half of the LLOQ for GMT computations purpose. Participants who received a licensed/authorized vaccine were censored at the day after receiving the licensed/authorized vaccine.

  Day 29 and Day 43

Secondary Outcomes (9)

• Number of Participants Who Experienced a Solicited Adverse Event (AE) Occurring on the Day of Booster Vaccination and the Following 7 Days

  Up to 7 days after booster vaccination (Days 57 to 64 and Days 180 to 187)

• Intensity of Solicited AEs Per FDA Toxicity Grading Scale Occurring on the Day of Booster Vaccination and the Following 7 Days

  Up to 7 days after booster vaccination (Days 57 to 64 and Days 180 to 187)

• Duration of Solicited AEs Occurring on the Day of Booster Vaccination and the Following 7 Days

  Up to 7 days after booster vaccination (Days 57 to 64 and Days 180 to 187)

• Number of Participants Who Experienced an Unsolicited AE Occurring on the Day of Booster Vaccination and the Following 28 Days

  Up to 28 days after booster vaccination (Days 57 to 85 and Days 180 to 208)

• Intensity of Unsolicited AEs Per the Investigator's Assessment Occurring on the Day of Booster Vaccination and the Following 28 Days

  Up to 28 days after booster vaccination (Days 57 to 85 and Days 180 to 208)

Study Arms (10)

Part 1, Group 1: CVnCoV 6 μg

EXPERIMENTAL

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.

Biological: CVnCoV 6 μg

Part 1, Group 2: CVnCoV 6 μg

EXPERIMENTAL

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

Biological: CVnCoV 6 μg

Part 1, Group 3: CVnCoV 12 μg

EXPERIMENTAL

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.

Biological: CVnCoV 12 μg

Part 1, Group 4: CVnCoV 12 μg

EXPERIMENTAL

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.

Biological: CVnCoV 12 μg

Part 1, Group 5: Hepatitis A vaccine

ACTIVE COMPARATOR

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.

Biological: Hepatitis A vaccine

Part 1, Group 6: Pneumococcal vaccine

ACTIVE COMPARATOR

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.

Biological: Pneumococcal vaccine

Part 2, Group 1: CVnCoV 12 µg

EXPERIMENTAL

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.

Biological: CVnCoV 12μg

Part 2, Group 2: Hepatitis A vaccine

ACTIVE COMPARATOR

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.

Biological: Hepatitis A vaccine

Part 2, Group 3: CVnCoV 12 µg

EXPERIMENTAL

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.

Biological: CVnCoV 12μg

Part 2, Group 4: Pneumococcal vaccine

ACTIVE COMPARATOR

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.

Biological: Pneumococcal vaccine

Interventions

CVnCoV 6 μg BIOLOGICAL

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

Also known as: CV07050101

Part 1, Group 1: CVnCoV 6 μg; Part 1, Group 2: CVnCoV 6 μg

CVnCoV 12 μg BIOLOGICAL

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

Also known as: CV07050101

Part 1, Group 3: CVnCoV 12 μg; Part 1, Group 4: CVnCoV 12 μg

Hepatitis A vaccine BIOLOGICAL

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

Part 1, Group 5: Hepatitis A vaccine; Part 2, Group 2: Hepatitis A vaccine

Pneumococcal vaccine BIOLOGICAL

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

Part 1, Group 6: Pneumococcal vaccine; Part 2, Group 4: Pneumococcal vaccine

CVnCoV 12μg BIOLOGICAL

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

Also known as: CV07050101

Part 2, Group 1: CVnCoV 12 µg; Part 2, Group 3: CVnCoV 12 µg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• CureVac: lead
• German Federal Ministry of Education and Research: collaborator

Study Sites (2)

Centro de vacunación internacional - CEVAXIN Panama Clinic

Panama City, 0831, Panama

Location

Instituto de Investigación Nutricional

Lima, Lima - 12, Peru

Location

MeSH Terms

Conditions

Coronavirus Infections; COVID-19; Severe Acute Respiratory Syndrome

Interventions

CVnCoV COVID-19 vaccine; Hepatitis A Vaccines; Pneumococcal Vaccines

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Viral Hepatitis Vaccines; Viral Vaccines; Vaccines; Biological Products; Complex Mixtures; Streptococcal Vaccines; Bacterial Vaccines

Results Point of Contact

• Title: Clinical Trial Information
• Organization: CureVac AG

clinicaltrials@curevac.com

0049 6976805870

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 13, 2020
• First Posted: August 17, 2020
• Study Start: September 21, 2020
• Primary Completion: February 21, 2022
• Study Completion: February 21, 2022
• Last Updated: September 28, 2023
• Results First Posted: September 28, 2023

Record last verified: 2023-09

Locations

PE (1); PA (1)