Safety, Reactogenicity, and Immunogenicity Trial of CV2CoV mRNA Vaccine Against SARS-CoV-2 in Seropositive Adult Participants

A Phase 1, Open-label, Safety, Reactogenicity, and Immunogenicity Trial of the CV2CoV mRNA Vaccine Against SARS CoV 2 in Seropositive Adult Participants

Prevention of COVID-19 caused by SARS-CoV-2.

Study Overview

• Status: Completed
• Conditions: SARS-CoV-2
• Intervention / Treatment: Biological: CV2CoV (2 µg); Biological: CV2CoV (4 µg); Biological: CV2CoV (8 µg); Biological: CV2CoV (12 µg); Biological: CV2CoV (16 µg); Biological: CV2CoV (20 µg)

• Study Type: Interventional
• Enrollment (Actual): 98
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80012-4520
      • Lynn Institute of Denver - ERN
  • Florida
    • Hallandale Beach, Florida, United States, 33009
      • MD Clinical - Velocity
    • Lakeland, Florida, United States, 33803
      • Accel Research Sites
    • Miami, Florida, United States, 33173
      • Suncoast Research Group LLC - ERN-PPDS
  • Illinois
    • Oak Brook, Illinois, United States, 60523
      • Affinity Health Corp
  • Ohio
    • Cleveland, Ohio, United States, 44122
      • Velocity Clinical Research - Cleveland
  • Oklahoma
    • Norman, Oklahoma, United States, 73072
      • Lynn Institute of Norman - ERN - PPDS
    • Oklahoma City, Oklahoma, United States, 73112
      • Lynn Health Science Institute
  • Texas
    • Plano, Texas, United States, 75093
      • Research Your Health - Elite
    • Tomball, Texas, United States, 77375
      • DM Clinical - Cyfair Clinical Research Center
  • Utah
    • West Jordan, Utah, United States, 84088
      • Velocity Clinical Research - Salt Lake City - Jordan Valley-ERN-PPDS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Must provide documented informed consent prior to any study procedures being performed.
2. Is capable of understanding and agrees to comply with planned study procedures and to be available for all study visits, including being willing and able to use electronic devices during the study.
3. Has received at least 2 doses of Pfizer-BioNTech (Comirnaty) or Moderna (Spikevax) mRNA COVID-19 vaccine with the last dose of vaccine received at least 6 months prior to Screening and has provided documentation of receiving the vaccination series.
4. Negative for SARS-CoV-2 infection by RT-PCR test at Screening.
5. Is a male or nonpregnant female 18 to <65 years of age (younger adult group) or ≥65 years of age (older adult group) at Screening.
6. Has a body mass index of 18 to 34.9 kg/m^2, inclusive, at Screening.
7. If the participant is a woman of child bearing potential the participant agrees to practice true abstinence or use at least 1 highly effective form of contraception for at least 30 days prior to study vaccination up to 3 months after study vaccination.
8. Agrees to refrain from blood or plasma donation from Screening and throughout the end of the study.
9. Is healthy or medically stable as determined by medical history, clinical laboratory tests, vital sign measurements, and physical examination findings, as determined by investigator judgment.

Exclusion Criteria:

1. Participant is female and has a positive serum pregnancy test result at Screening or plans to become pregnant during the study.
2. Participant is female and is breastfeeding or plans to breastfeed from study vaccination to 3 months after study vaccination.
3. Has any clinically significant abnormal biochemistry or hematology finding (defined as ≥Grade 1) at Screening.
4. Has any medical disease or condition that, in the opinion of the investigator, precludes study participation. This includes any acute, subacute, intermittent, or chronic medical disease or condition that would place the participant at an unacceptable risk of injury, render the participant unable to meet the requirements of the protocol, or may interfere with the evaluation of responses or the participant's successful completion of the trial.
5. Any confirmed or suspected immunosuppressive or immunodeficient condition resulting from disease or immunosuppressive/cytotoxic therapy.
6. History of myocarditis, pericarditis, or idiopathic cardiomyopathy, or presence of any medical condition that increases risk of myocarditis or pericarditis, including cocaine abuse, cardiomyopathy, endomyocardial fibrosis, hypereosinophilic syndrome, hypersensitivity myocarditis, eosinophilic granulomatosis with polyangiitis, persistent myocardial viral infection (eg, due to enterovirus or adenovirus), and celiac disease.
7. Has an acute febrile illness with a temperature ≥38.0°C or ≥100.4°F observed by the participant or at the study site within 72 hours prior to study vaccination. Participants with suspected COVID-19 symptoms should be excluded and referred for medical care.
8. Has a prior confirmed diagnosis of chronic hepatitis B, hepatitis C, or HIV 1/2 infection or evidence of active infection at Screening.
9. Has participated or plans to participate in another investigational study involving any investigational drug or device within 60 days or 5 half-lives, whichever is longer, before study vaccination and throughout the end of the study.
10. Has previously participated in an investigational vaccine study with investigational vaccine administered within 6 months of study vaccination OR has received the last dose of >1 COVID-19 vaccine series (investigational and/or authorized) in the last 12 months.
11. Has received or plans to receive any licensed vaccine within 4 weeks before or after study vaccination. Inactivated vaccines for influenza are permitted during the study if they are administered at least 14 days before or after study vaccination.
12. Is planning to receive a COVID-19 booster vaccination for the duration of the study (for adults who are not covered by local recommendations to receive booster per current standard of care) or is planning to receive a COVID-19 booster vaccination on or before Day 29 of the study (for adults covered by local recommendations to receive booster).
13. Has received or plans to receive immunoglobulins or any blood or blood products within 90 days before study vaccination and throughout the study.
14. Has a history of hypersensitivity or severe allergic reaction, including anaphylaxis, generalized urticaria, angioedema, and other significant reactions to any previous vaccine or any component of the IP.
15. Has a history of hypersensitivity or severe allergic reaction (including anaphylaxis, generalized urticaria, angioedema, and other significant reactions) to beta lactam antibiotics.
16. Reports chronic use (more than 14 continuous days) of any medication that may be associated with changes in immune function including, but not limited to, systemic corticosteroids exceeding 10 mg/day of prednisone equivalent, allergy injections, immunoglobulins, interferons, immunomodulators, cytotoxic drugs, or other similar or toxic drugs within 6 months of study vaccination.
17. Has a bleeding disorder or prior history of significant bleeding or bruising after IM injections or venipuncture.
18. Has a history of alcohol abuse or other recreational drug use (excluding cannabis) within 6 months before study vaccination.
19. Has any abnormal skin condition or permanent body art that would interfere with the ability to observe local reactions at the study vaccination injection site.
20. Has had known close contact with anyone who had a confirmed SARS-CoV-2 infection within 14 days before study vaccination.
21. Participant is an employee or family member of the investigator or study site personnel.

22. Has any self-reported or medically-documented significant medical or psychiatric condition. Significant medical conditions include, but are not limited to, the following:

    1. Moderate or severe respiratory disease
    2. Uncontrolled hypertension, defined as an average systolic blood pressure ≥140 mmHg for participants ≤60 years old, and ≥150 mmHg for participants >60 years old, or a diastolic blood pressure ≥90 mmHg for any age
    3. Significant cardiovascular disease or history of myocarditis or pericarditis
    4. Neurological or neurodevelopmental conditions
    5. Ongoing malignancy or recent diagnosis of malignancy in the last 5 years (excluding basal cell and squamous cell carcinoma of the skin)
    6. Tuberculosis or nontuberculosis mycobacterial infection
    7. Autoimmune disease, including hypothyroidism without a defined nonautoimmune cause
    8. Immunodeficiency of any cause, including from solid organ transplant, blood or bone marrow transplant, use of corticosteroids, or use of other immune weakening medicines
    9. Type 1 or 2 diabetes mellitus regardless of disease control

23. Has any of the following self-reported or medically-documented risk factors for severe COVID-19:

    1. Cancer
    2. Chronic kidney disease
    3. Sickle cell disease
    4. Cerebrovascular disease
    5. Cystic fibrosis
    6. Chronic liver disease
    7. Pulmonary fibrosis
    8. Thalassemia
    9. Smoking or other inhaled substance use, including tobacco, cannabis, or nicotine vapors, with an average of ≥5 cigarettes a day or equivalent (currently or within 1 year of Screening).
24. Has a history of documented SARS-CoV-2 infection or COVID-19 within 6 months before Screening.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CV2CoV Dose Cohort 1 (2µg or 4µg); Group 1a will receive CV2CoV dose level 2 µg; Group 1b will receive CV2CoV dose level 4 µg	Biological: CV2CoV (2 µg); Study vaccine will be administered as a single intramuscular injection in the deltoid area, preferably in the nondominant arm.; Biological: CV2CoV (4 µg); Study vaccine will be administered as a single intramuscular injection in the deltoid area, preferably in the nondominant arm.
Experimental: CV2CoV Dose Cohort 2 (8 µg); Cohort 2 will receive CV2CoV dose level 8 µg Enrollment into Cohort 2 will begin after the Safety Review Team (SRT) has reviewed safety data from 2 sentinel participants from the previous dose cohort.	Biological: CV2CoV (8 µg); Study vaccine will be administered as a single intramuscular injection in the deltoid area, preferably in the nondominant arm.
Experimental: CV2CoV Dose Cohort 3 (12 µg); Cohort 3 will receive CV2CoV dose level 12 µg Enrollment into Cohort 3 will begin after the SRT has reviewed safety data from 2 sentinel participants from the previous dose cohort.	Biological: CV2CoV (12 µg); Study vaccine will be administered as a single intramuscular injection in the deltoid area, preferably in the nondominant arm.
Experimental: CV2CoV Dose Cohort 4 (16 µg); Cohort 4 will receive CV2CoV dose level 16 µg Enrollment into Cohort 4 will begin after the SRT has reviewed safety data from all participants in the previous dose cohort.	Biological: CV2CoV (16 µg); Study vaccine will be administered as a single intramuscular injection in the deltoid area, preferably in the nondominant arm.
Experimental: CV2CoV Dose Cohort 5 (20 µg); Cohort 5 will receive CV2CoV dose level 20 µg Enrollment into Cohort 5 will begin after the SRT has reviewed safety data from all participants in the previous dose cohort.	Biological: CV2CoV (20 µg); Study vaccine will be administered as a single intramuscular injection in the deltoid area, preferably in the nondominant arm.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of participants with adverse events of special interest (AESIs) from study vaccination through the end of the study	An AESI (serious or nonserious) is defined as an AE or SAE of scientific and medical concern specific to the sponsor's product or program, for which ongoing monitoring and rapid communication by the investigator to the sponsor could be appropriate.	180 days after the study vaccine administration
Percentage of participants with serious adverse events (SAEs) from study vaccination through the end of the study	An SAE is defined as any event that: Results in death; Is immediately life-threatening; Requires inpatient hospitalization or prolongation of existing hospitalization; Results in persistent or significant disability/incapacity; Is a congenital anomaly/birth defect; Is a spontaneous miscarriage Important medical events that may not result in death, be life-threatening, or require hospitalization may be considered SAEs when, based upon appropriate medical judgment, they may jeopardize the participant or may require medical or surgical intervention to prevent one of the outcomes listed in this definition. Examples of such medical events include allergic bronchospasm requiring intensive treatment in an emergency room or at home, blood dyscrasias or convulsions that do not result in inpatient hospitalization, or the development of drug dependency or drug abuse.	180 days after the study vaccine administration
Percentage of participants with medically attended adverse events (MAAEs) from study vaccination through the end of the study	An MAAE is defined as an AE that results in a visit to a medical professional. Medically attended visits are defined as a telemedicine visit, physician's office visit, urgent care visit, emergency room visit, hospitalization, or death.	180 days after the study vaccine administration
Percentage of participants with solicited local adverse events (AEs) up to 7 days after study vaccination	Local solicited AEs will include injection site pain, redness, swelling, and lymphadenopathy.	Days 1 to 7
Percentage of participants with each solicited systemic AEs up to 7 days after study vaccination	Systemic solicited events will include fever, headache, fatigue, myalgia, arthralgia, and chills.	Days 1 to 7
Percentage of participants with unsolicited AEs up to 28 days after study vaccination, including clinically relevant abnormal clinical safety laboratory findings	An unsolicited AE is defined as any AE that is volunteered from the participant and occurs within 28 days after vaccination.	28 days after the study vaccine administration

Secondary Outcome Measures

Outcome Measure	Time Frame
Geometric Mean Titers (GMTs) of neutralizing antibody titers against pseudovirus bearing spike protein from SARS CoV 2 wild type (WT) at each collection time point	Days 1, 8, 15, 29, 85, and 180
Percentage of participants with seroresponse (≥4 fold rise from baseline) at Day 29 after the booster dose	29 days post booster dose
Geometric Mean Increase (GMI) from baseline of neutralizing antibody titers against pseudovirus bearing spike protein from SARS CoV 2 WT at each collection time point	Days 8, 15, 29, 85, and 180
GMTs of binding Immunoglobulin G (IgG) against SARS CoV-2 S protein and Receptor-Binding Domain (RBD) at each collection time point.	Days 8, 15, 29, 85, 180
GMI from baseline of binding IgG against SARS CoV-2 S protein and RBD at each collection time point	Day 8, 15, 29, 85, 180

Collaborators and Investigators

• Sponsor: GlaxoSmithKline
• Collaborators: CureVac

Study record dates

Study Major Dates

• Study Start (Actual): March 24, 2022
• Primary Completion (Actual): March 7, 2023
• Study Completion (Actual): March 7, 2023

Study Registration Dates

• First Submitted: February 25, 2022
• First Submitted That Met QC Criteria: February 25, 2022
• First Posted (Actual): March 2, 2022

Study Record Updates

• Last Update Posted (Actual): April 10, 2023
• Last Update Submitted That Met QC Criteria: April 7, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: COVID-19; Pandemic; Booster vaccination
• Other Study ID Numbers: 217741

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
• IPD Sharing Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data of the study.
• IPD Sharing Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No