Safety and Immunogenicity Study of a Booster Dose of the Investigational CV0501 mRNA COVID-19 Vaccine in Adults at Least 18 Years Old

Phase 1

Completed

Conditions: COVID-19
SARS-CoV-2

Interventions: Biological: CV0501 (12 μg)
Biological: CV0501 (25 μg)
Biological: CV0501 (50 μg)
Biological: CV0501 (100 μg)
Biological: CV0501 (200 μg)
Biological: CV0501 (6 μg)
Biological: CV0501 (3 μg)
Biological: CV0501 (75 μg)
Biological: CV0501 (150 μg)

Registration Number: NCT05477186

Lead Sponsor: GlaxoSmithKline

Brief Summary: Prevention of COVID-19 caused by SARS-CoV-2.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 185

Inclusion Criteria

Must provide documented informed consent prior to any study procedures being performed
Is capable of understanding and agrees to comply with planned study procedures and to be available for all study visits
Has received at least 2 doses of Comirnaty or Moderna COVID-19 Vaccine (Spikevax®\), with the last dose of vaccine received at least 6 months prior to screening
Negative for SARS-CoV-2 infection by RT-PCR test at screening
Is a male or nonpregnant female >= 18 years old
If the participant is a woman of childbearing potential, the participant agrees to use at least 1 highly effective form of contraception for at least 30 days prior to the study vaccination up to 3 months after study vaccination.
Agrees to refrain from blood or plasma donation from the first study vaccination through end of study.
Has a body mass index of 18 to 40 kg/m^2, inclusive, at screening.
Is healthy or medically stable as determined by investigator judgment based on medical history, clinical laboratory tests, vital sign measurements, and physical examination findings

Exclusion Criteria

Participant is female and has a positive pregnancy test result at screening.
Participant is female and is breastfeeding or will (re)start breastfeeding from the study vaccination to 3 months after vaccination.
Has an acute febrile illness with temperature >=38.0°C or >=100.4°F within 72 hours before study vaccination. Individuals with suspected COVID-19 symptoms should be excluded and referred for medical care.
Has a history of documented SARS-CoV-2 infection or COVID-19 within 6 months before screening.
Has a documented medical history of HIV, hepatitis B or hepatitis C infection prior to screening, or a positive test for these conditions at screening.
Any confirmed or suspected immunosuppressive or immunodeficient condition resulting from disease (eg, malignancy) or immunosuppressive/cytotoxic therapy (eg, medications used during cancer chemotherapy, organ transplantation or to treat autoimmune disorders). 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 immunotherapy injections, immunoglobulin, interferon, immunomodulators, cytotoxic drugs, or other similar or toxic drugs within 6 months of the first study vaccination. Inclusion of persons who use low dose topical, ophthalmic, inhaled, or intranasal steroid preparations is permitted.
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.
Has a new onset, clinically significant, abnormal biochemistry or hematology finding (defined as >= Grade 1) at screening (adults with Grade 1 laboratory abnormalities that have been stable for at least 6 months before enrollment may be included in the study).
Individuals with a history of autoimmune disease or an active autoimmune disease requiring therapeutic intervention, including but not limited to: systemic or cutaneous lupus erythematosus, autoimmune arthritis/rheumatoid arthritis, Guillain- Barré syndrome, multiple sclerosis, Sjögren's syndrome, idiopathic thrombocytopenia purpura, glomerulonephritis, autoimmune thyroiditis, giant cell arteritis (temporal arteritis), Takayasu arteritis, granulomatosis with polyangiitis, psoriasis, and insulin-dependent diabetes mellitus (Type 1).
Has an unstable chronic medical condition. This refers to a condition requiring a new medication or increase in dose of current medication(s) or a condition requiring hospitalization within 6 months prior to screening.
Has a history of hypersensitivity or severe allergic reaction, including anaphylaxis, generalized urticaria, angioedema, and other significant reactions, to vaccines or to any component of the investigational product.
Has received or plans to receive any licensed vaccine, within 4 weeks before or 4 weeks 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.
Has had known close contact with anyone who had a confirmed SARS-CoV-2 infection within 2 weeks before study vaccination. Rescreening of these participants permitted after quarantine period is complete.
Has participated or plans to participate in another investigational study involving any investigational product or device within 6 months or 5 half-lives, whichever is longer, before the study vaccination through end of study.
Has received or plans to receive immunoglobulins or any blood or blood products within 3 months before the first study vaccination through end of study.
Has a bleeding diathesis or condition associated with prolonged bleeding that would, in the opinion of the investigator, contraindicate intramuscular injection.
Has a history of alcohol abuse or other recreational drug use (excluding cannabis) within 6 months before study vaccination.
Has any abnormal skin condition or permanent body art (eg, tattoo) that would interfere with the ability to observe local reactions at the injection site.
Has a medical disease or psychiatric condition that, in the opinion of the investigator, precludes study participation because it would place the individual at an unacceptable risk of injury, render the individual unable to meet the requirements of the protocol or interfere with the individual's successful completion of the trial.
Participant is an employee or family member of the investigator or study site personnel.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Part A: CV0501 Dose Cohort 1 (12 μg)	CV0501 (12 μg)	Healthy participants received a single dose of 12 microgram (μg) CV0501 vaccine intramuscularly at Day 1.
Part A: CV0501 Dose Cohort 2 (25 μg)	CV0501 (25 μg)	Healthy participants received a single dose of 25 μg CV0501 vaccine intramuscularly at Day 1.
Part A: CV0501 Dose Cohort 3 (50 μg)	CV0501 (50 μg)	Healthy participants received a single dose of 50 μg CV0501 vaccine intramuscularly at Day 1.
Part A: CV0501 Dose Cohort 4 (100 μg)	CV0501 (100 μg)	Healthy participants received a single dose of 100 μg CV0501 vaccine intramuscularly at Day 1.
Part A: CV0501 Dose Cohort 5 (200 μg)	CV0501 (200 μg)	Healthy participants received a single dose of 200 μg CV0501 vaccine intramuscularly at Day 1.
Part B: CV0501 Dose Cohort 6 (3 μg)	CV0501 (6 μg)	Healthy participants received a single dose of 3 μg CV0501 vaccine intramuscularly at Day 1.
Part B: CV0501 Dose Cohort 7 (6 μg)	CV0501 (3 μg)	Healthy participants received a single dose of 6 μg CV0501 vaccine intramuscularly at Day 1.
Part A: CV0501 Dose Cohort 4 (75 μg or 100 μg)	CV0501 (100 μg)	For each of the groups in Cohort 4, Group 4a (younger) and Group 4b (older age),the SRT may recommend a dose specified by the dosing scenarios in the protocol, based on their review of all available safety data. The SRT will use the same approach, independently, to select the dose levels for older participants (Group 4b) and younger participants (Group 4a).
Part A: CV0501 Dose Cohort 3 (50 μg)	CV0501 (50 μg)	For both Group 3a (younger) and Group 3b (older age), initiation of enrollment in the subsequent group at the next dose level for Cohorts 2-5 will depend on SRT review of safety data up to Day 8 from a minimum of 10 participants, from the previous dose level in the same age group.
Part A: CV0501 Dose Cohort 5 (100 μg, 150 μg or 200 μg)	CV0501 (150 μg)	For each of the groups in Cohort 5, Group 5a (younger) and Group 5b (older age), the SRT may recommend a dose specified by the dosing scenarios in the protocol, based on their review of all available safety data. The SRT will use the same approach, independently, to select the dose levels for older participants (Group 5b) and younger participants (Group 5a).
Part B: CV0501 Dose Cohort 7 (6 μg)	CV0501 (3 μg)	Part B, designed to comprise 2 single age group cohorts, Group 7a (≥18 to \<65 years old) will start based on the first interim analysis of safety and immunogenicity data, provided that the SRT assesses the 12 μg dose to be immunogenic and safe.
Part A: CV0501 Dose Cohort 1 (12 μg)	CV0501 (12 μg)	Enrollment will be staggered, beginning with Group 1a (12 μg, younger adults). Initiation of enrollment in Group 1b (12 μg, older adults) will depend on Safety Review Team (SRT) review of safety data up to Day 8 from a minimum of 10 participants in Group 1a.
Part A: CV0501 Dose Cohort 2 (25 μg)	CV0501 (25 μg)	For both Group 2a (younger) and Group 2b (older age), initiation of enrollment in the subsequent group at the next dose level for Cohorts 2-5 will depend on SRT review of safety data up to Day 8 from a minimum of 10 participants, from the previous dose level in the same age group.
Part A: CV0501 Dose Cohort 4 (75 μg or 100 μg)	CV0501 (75 μg)	For each of the groups in Cohort 4, Group 4a (younger) and Group 4b (older age),the SRT may recommend a dose specified by the dosing scenarios in the protocol, based on their review of all available safety data. The SRT will use the same approach, independently, to select the dose levels for older participants (Group 4b) and younger participants (Group 4a).
Part A: CV0501 Dose Cohort 5 (100 μg, 150 μg or 200 μg)	CV0501 (100 μg)	For each of the groups in Cohort 5, Group 5a (younger) and Group 5b (older age), the SRT may recommend a dose specified by the dosing scenarios in the protocol, based on their review of all available safety data. The SRT will use the same approach, independently, to select the dose levels for older participants (Group 5b) and younger participants (Group 5a).
Part A: CV0501 Dose Cohort 5 (100 μg, 150 μg or 200 μg)	CV0501 (200 μg)	For each of the groups in Cohort 5, Group 5a (younger) and Group 5b (older age), the SRT may recommend a dose specified by the dosing scenarios in the protocol, based on their review of all available safety data. The SRT will use the same approach, independently, to select the dose levels for older participants (Group 5b) and younger participants (Group 5a).
Part B: CV0501 Dose Cohort 6 (3 μg)	CV0501 (6 μg)	Part B, designed to comprise 2 single age group cohorts, Group 6a (≥18 to \<65 years old) will start based on the first interim analysis of safety and immunogenicity data, provided that the SRT assesses the 12 μg dose to be immunogenic and safe.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Solicited Local Adverse Events (AE) During 7 Days After Vaccination	From Day 1 to Day 7 (including Day 7)	Assessed solicited local adverse events were injection site pain, redness, swelling, and Lymphadenopathy.
Number of Participants With Solicited Systemic AE During 7 Days After Vaccination	From Day 1 to Day 7 (including Day 7)	Assessed solicited systemic AEs were fever, headache, fatigue, myalgia, arthralgia, and chills.
Number of Participants With Unsolicited AEs for 28 Days After Study Vaccination	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 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 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 serious adverse event (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 Each Abnormal Clinical Safety Laboratory Finding for 8 Days After Study Vaccination	8 days from vaccination at Day 1	An abnormal laboratory is defined as any value outside of the normal range. Normal ranges were: Alanine Aminotransferase: (Female: 10-32 micro (u)/ liter (L); Male: 10-40 u/L); Alkaline Phosphatase: (Female: 30-115 u/L; Male: 43-115 u/L); Aspartate Aminotransferase: (Female: 10-36 u/L; Male: 10-43 u/L); Bilirubin total: 0.1-1.1 milligram (mg)/deciliter (dL); Bilirubin, Direct: 0-0.4 mg/dL ;Creatinine:0.7-1.4 mg/dL; Eosinophils: 0%-7%; Eosinophils/Leukocytes: 0.00-0.80 x 10\^3/uL ; Erythrocytes: (Female: 3.70-5.20 x 10\^6/uL; Male: 4.63-6.08x 10\^6/uL); Hemoglobin: (Female: 11.0-15.5 gram (g)/dL; Male: 12.5-17.0 g/dL); Leukocytes: 3.70-11.00 x 10\^3/uL; Lymphocytes 12.0%-46.0%; Lymphocytes/Leukocytes: 0.90-3.60 x 10\^3/uL; Monocytes/Leukocytes: 0.00-1.20 x 10\^3/uL; Neutrophils: 4.0% - 71.0%; Neutrophils/Leukocytes:1.70-7.90x 10\^3/uL; Platelets: 163-375 x 10\^3/uL; Urea Nitrogen: 5-20 mg/dL.

Secondary Outcome Measures

Name	Time	Method
Geometric Mean Titers (GMTs) of Neutralizing Antibody (Ab) Against Pseudovirus Bearing S Protein From SARS-CoV-2 WT, Omicron, and Delta Variants at Each Collection Timepoint	At Day 1, Day 15, Day 29, Day 91, and Day 181
Geometric Mean Increase (GMI) From Baseline of Neutralizing Ab Titers Against Pseudovirus Bearing S Protein From SARS-CoV-2 WT, Omicron, and Delta Variants at Each Collection Time Point	At Day 15, Day 29, Day 91, and Day 181
Percentage of Participants With Neutralizing Seroresponse of Serum SARS-CoV-2 WT, Omicron BA.1, BA.2 and BA.5 Variants Specific Ab at Day 29	At day 29 (28 days after the booster dose)	Seroresponse was defined as post-boost titers \>= 4 times pre-boost (baseline) titers for participants with titer \>= LLOQ at pre-vaccination and as post-booster titer \>= 4 times LLOQ for participants with titer \< LLOQ at pre vaccination.