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

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT05260437

Enrollment

Registered

2022-03-02

Start date

2022-03-24

Completion date

2023-03-07

Last updated

2024-08-12

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

COVID-19, SARS-CoV-2

Keywords

COVID-19, Pandemic, Booster vaccination

Brief summary

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

Interventions

BIOLOGICALCV2CoV (2 µg)

Study vaccine was administered as a single intramuscular injection.

BIOLOGICALCV2CoV (4 µg)

Study vaccine was administered as a single intramuscular injection.

BIOLOGICALCV2CoV (8 µg)

Study vaccine was administered as a single intramuscular injection.

BIOLOGICALCV2CoV (12 µg)

Study vaccine was administered as a single intramuscular injection.

BIOLOGICALCV2CoV (16 µg)

Study vaccine was administered as a single intramuscular injection.

BIOLOGICALCV2CoV (20 µg)

Study vaccine was planned to be administered intramuscularly. No vaccine was administered in the CV2CoV (20 µg) Group, since there were no participants enrolled in it.

Study design

Allocation

NON_RANDOMIZED

Intervention model

SEQUENTIAL

Primary purpose

PREVENTION

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Yes

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.

Design outcomes

Primary

Measure	Time frame	Description
Number of Participants With Unsolicited AEs up to 28 Days After Study Vaccination, Including Clinically Relevant Abnormal Clinical Safety Laboratory Findings	From Day 1 to Day 28 (including Day 28)	An unsolicited AE is defined as any AE that is volunteered from the participant and occurs within 28 days after vaccination.
Number of Participants With Adverse Events of Special Interest (AESIs) From Study Vaccination Through the End of the Study	From Day 1 up to Day 180 (including Day 180)	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.
Number of Participants With Serious Adverse Events (SAEs) From Study Vaccination Through the End of the Study	From Day 1 up to Day 180 (including Day 180)	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.
Number of Participants With Medically Attended Adverse Events (MAAEs) From Study Vaccination Through the End of the Study	From Day 1 up to Day 180 (including Day 180)	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.
Number of Participants With Solicited Local Adverse Events (AEs) up to 7 Days After Study Vaccination	From Day 1 to Day 7 (including Day 7)	Assessed solicited local reactions were injection site pain, redness, swelling, and lymphadenopathy.
Number of Participants With Each Solicited Systemic AEs up to 7 Days After Study Vaccination	From Day 1 to Day 7 (including Day 7)	Assessed solicited systemic reactions were fever, headache, fatigue, myalgia, arthralgia, and chills.

Secondary

Measure	Time frame	Description
Percentage of Participants With Seroresponse (>= 4 Fold Rise From Baseline) at Day 29 After the Booster Dose	At Day 29 (29 days post booster dose)	Percentage of participants with seroresponse against antigen SARS-CoV-2 WT, Beta, Omicron BA.1, Omicron BA.2, Delta assessed were reported. Seroresponse was defined as greater than equal to (\>=) 4-fold increase from Day 1 (Baseline) to the Day 29. The fold rise was calculated as the ratio of the post-vaccination Neutralizing Antibody Titers to the pre-vaccination Neutralizing Antibody Titers.
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	At Day 8, Day 15, Day 29, Day 85, and Day 180	—
GMTs of Binding Immunoglobulin G (IgG) Against SARS CoV-2 S Protein and Receptor-Binding Domain (RBD)	At Day 8, Day 15, Day 29, Day 85 and Day 180	—
GMI From Baseline of Binding IgG Against SARS CoV-2 S Protein and RBD	At Day 8, Day 15, Day 29, Day 85, and Day 180	—
Geometric Mean Titers (GMTs) of Neutralizing Antibody Titers Against Pseudovirus Bearing Spike Protein From SARS CoV 2 Wild Type (WT)	At Day 1, Day 8, Day 15, Day 29, Day 85, and Day 180	—

Countries

United States

Participant flow

Recruitment details

The study was conducted at 13 centers in the United States.

Pre-assignment details

Escalation to the next higher dose cohorts was based on the Safety Review Team (SRT) review of safety data from the same age group. GlaxoSmithKline Biologicals SA (GSK) and CureVac decided to stop further enrollment or vaccination in the CV2-SARS-CoV-2-002 (217741) dose escalation study. This decision was taken because the data accumulated were considered sufficient to determine next steps in vaccine platform development. Therefore, enrollment in CV2CoV Dose Cohort 5 (20 µg) was never opened.

Participants by arm

Arm	Count
CV2CoV Dose Cohort 1 (Group 1a 2µg) Participants received 2 µg CV2CoV intramuscularly.	24
CV2CoV Dose Cohort 1 (Group 1b 4µg) Participants received 4 µg CV2CoV intramuscularly.	23
CV2CoV Dose Cohort 2 (8 µg) Participants received 8 µg CV2CoV intramuscularly.	20
CV2CoV Dose Cohort 3 (12 µg) Participants received 12 µg CV2CoV intramuscularly.	21
CV2CoV Dose Cohort 4 (16 µg) Participants received 16 µg CV2CoV intramuscularly.	11
Total	99

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003	FG004
Overall Study	Lost to Follow-up	5	2	1	2	2
Overall Study	Vaccine Not Administered	0	1	0	0	0
Overall Study	Withdrawal by Subject	3	0	4	5	0

Baseline characteristics

Characteristic	CV2CoV Dose Cohort 1 (Group 1a 2µg)	CV2CoV Dose Cohort 1 (Group 1b 4µg)	CV2CoV Dose Cohort 2 (8 µg)	CV2CoV Dose Cohort 3 (12 µg)	CV2CoV Dose Cohort 4 (16 µg)	Total
Age, Continuous	42.5 Years STANDARD_DEVIATION 15.46	44.8 Years STANDARD_DEVIATION 14.87	43.9 Years STANDARD_DEVIATION 15.77	39.7 Years STANDARD_DEVIATION 12.37	37.6 Years STANDARD_DEVIATION 10.69	42.2 Years STANDARD_DEVIATION 14.24
Ethnicity (NIH/OMB) Hispanic or Latino	8 Participants	8 Participants	11 Participants	15 Participants	5 Participants	47 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	16 Participants	15 Participants	9 Participants	6 Participants	5 Participants	51 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	1 Participants
Sex: Female, Male Female	17 Participants	10 Participants	8 Participants	10 Participants	3 Participants	48 Participants
Sex: Female, Male Male	7 Participants	13 Participants	12 Participants	11 Participants	8 Participants	51 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk
deaths Total, all-cause mortality	0 / 24	0 / 22	0 / 20	0 / 21	0 / 11
other Total, other adverse events	18 / 24	17 / 22	16 / 20	18 / 21	9 / 11
serious Total, serious adverse events	0 / 24	2 / 22	0 / 20	0 / 21	0 / 11

Outcome results

Primary

Number 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.

Time frame: From Day 1 up to Day 180 (including Day 180)