A Phase 1/2, First-Time-in Human (FTiH), Randomized, Observer-blind, Placebo-controlled, Dose Escalation Study to Assess Safety, Reactogenicity and Immunogenicity of a Candidate Cytomegalovirus (CMV) Vaccine Comprising Recombinant Protein and Adjuvant When Administered Intramuscularly in Healthy Adults
Overview
- Phase
- Phase 1
- Intervention
- Pentamer (low)/gB(low)/Adjuvant vaccine
- Conditions
- Cytomegalovirus Infections
- Sponsor
- GlaxoSmithKline
- Enrollment
- 339
- Locations
- 18
- Primary Endpoint
- Number of participants reporting hematological and biochemical laboratory abnormalities on Day 1
- Status
- Completed
- Last Updated
- 2 months ago
Overview
Brief Summary
The purpose of this study is to assess the safety, reactogenicity and immune response of the candidate CMV recombinant protein subunit (CMVsu) vaccine consisting of a combination of glycoproteins B (gB) and pentamer antigens adjuvanted, regardless of baseline CMV sero-status. This FTiH study will be conducted in healthy adults 18 to 50 years of age, in which the 4 dose levels of the vaccine will be administered in a step-wise dose escalation manner, based upon safety adjudication.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Participants who, in the opinion of the investigator, can and will comply with the requirements of the protocol.
- •Written informed consent obtained from the participant prior to performance of any study specific procedure.
- •A healthy adult (woman or man), 18 to 50 years of age at the time of the first study intervention administration.
- •Healthy participants as established by medical history and clinical examination before entering the study.
- •Participants who are women of non-childbearing potential may be enrolled in the study.
- •Participants who are women of child-bearing potential may be enrolled in the study, if the participant:
- •has practiced adequate contraception for 30 days prior to study intervention administration, and
- •has a negative pregnancy test on the day of study intervention administration and
- •has agreed to continue adequate contraception during the entire treatment period and for 3 months after completion of the study intervention administration series.
- •Participants who agree to take appropriate infection control measures to prevent becoming infected with SARS-CoV2 during the study.
Exclusion Criteria
- •Medical conditions
- •Known documented medical history of or viral hepatitis B or C infection.
- •History of any reaction or hypersensitivity likely to be exacerbated by any component of the study intervention(s).
- •Any confirmed or suspected immunosuppressive or immunodeficient condition.
- •Family history of congenital or hereditary immunodeficiency.
- •History of or current autoimmune disease.
- •Lymphoproliferative disorder or malignancy within previous 5 years (excluding effectively treated non-melanotic skin cancer).
- •Hypersensitivity to latex.
- •Major congenital defects
- •Acute or chronic clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality.
Arms & Interventions
Pentamer(low)/gB(low)/Adjuvant Group
Participants receive the candidate CMVsu vaccine consisting of a combination of low dose pentamer and low dose gB antigens, adjuvanted at 0, 2 and 6 months and are followed up until end of study (Day 546).
Intervention: Pentamer (low)/gB(low)/Adjuvant vaccine
Pentamer (med)/gB(low)/Adjuvant Group
Participants receive the candidate CMVsu vaccine consisting of a combination of medium dose pentamer and low dose gB antigens, adjuvanted at 0, 2 and 6 months and are followed up until end of study (Day 546).
Intervention: Pentamer (med)/gB(low)/Adjuvant vaccine
Pentamer (med)/gB(med)/Adjuvant Group
Participants receive the candidate CMVsu vaccine consisting of a combination of medium dose pentamer and medium dose gB antigens, adjuvanted at 0, 2 and 6 months and are followed up until end of study (Day 546).
Intervention: Pentamer (med)/gB(med)/Adjuvant vaccine
Pentamer (high)/gB(med)/Adjuvant Group
Participants receive the candidate CMVsu vaccine consisting of a combination of high dose pentamer and medium dose gB antigens, adjuvanted at 0, 2 and 6 months and are followed up until end of study (Day 546).
Intervention: Pentamer (high)/gB(med)/Adjuvant vaccine
Placebo Group
Participants receive placebo (saline) at 0,2 and 6 months and are followed up until end of study (Day 546).
Intervention: Placebo (saline)
Outcomes
Primary Outcomes
Number of participants reporting hematological and biochemical laboratory abnormalities on Day 1
Time Frame: At Day 1
The percentage of participants having hematology and biochemistry results below or above the laboratory normal ranges are tabulated by time point.
Number of participants reporting solicited administration site events
Time Frame: Within 7 days (the day of dose and 6 subsequent days) after each dose (vaccines administered on Day 1, Day 61 and Day 181)
The solicited administration site events include pain, redness and swelling.
Number of participants reporting hematological and biochemical laboratory abnormalities on Day 68
Time Frame: At Day 68
The percentage of participants having hematology and biochemistry results below or above the laboratory normal ranges are tabulated by time point.
Number of participants reporting hematological and biochemical laboratory abnormalities on Day 181
Time Frame: At Day 181
The percentage of participants having hematology and biochemistry results below or above the laboratory normal ranges are tabulated by time point.
Number of participants reporting solicited systemic events
Time Frame: Within 7 days (the day of dose and 6 subsequent days) after each dose (vaccines administered on Day 1, Day 61 and Day 181)
The solicited systemic events include fever, myalgia, fatigue, arthralgia and headache. The preferred location for measuring temperature is the oral cavity. Fever is defined as body temperature ≥38.0°C/100.4°F by any route.
Number of participants reporting unsolicited adverse events (AEs) within 7 days after each dose
Time Frame: Within 7 days (the day of dose and 6 subsequent days) after each dose (vaccines administered on Day 1, Day 61 and Day 181)
An unsolicited AE is an AE that was not included in a list of solicited events using a Participant Diary. Also, any 'solicited' symptom with onset outside the specified period of follow-up for solicited symptoms is reported as an unsolicited adverse event.
Number of participants reporting serious adverse events (SAEs) within 7 days after each dose
Time Frame: Within 7 days (the day of dose and 6 subsequent days) after each dose (vaccines administered on Day 1, Day 61 and Day 181)
A SAE is any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study participant or is an abnormal pregnancy outcome.
Number of participants reporting SAEs up to 30 days after each dose
Time Frame: Up to 30 days after each dose (vaccines administered on Day 1, Day 61 and Day 181)
A SAE is any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study participant or is an abnormal pregnancy outcome.
Number of participants reporting unsolicited AEs up to 30 days after each dose
Time Frame: Up to 30 days after each dose (vaccines administered on Day 1, Day 61 and Day 181)
An unsolicited AE is an AE that was not included in a list of solicited events using a Participant Diary. Unsolicited events must have been spontaneously communicated by a participant who has signed the informed consent. Also, any 'solicited' symptom with onset outside the specified period of follow-up for solicited symptoms is reported as an unsolicited adverse event.
Number of participants reporting hematological and biochemical laboratory abnormalities on Day 8
Time Frame: At Day 8
The percentage of participants having hematology and biochemistry results below or above the laboratory normal ranges are tabulated by time point.
Number of participants reporting hematological and biochemical laboratory abnormalities on Day 188
Time Frame: Day 188
The percentage of participants having hematology and biochemistry results below or above the laboratory normal ranges are tabulated by time point.
Number of participants reporting medically attended AEs (MAEs) up to 30 days after each dose
Time Frame: Up to 30 days after each dose (vaccines administered on Day 1, Day 61 and Day 181)
A MAE is an AE for which the participants received medical attention defined as hospitalization, an emergency room visit or a visit to or from medical personnel for any reason.
Number of participants reporting hematological and biochemical laboratory abnormalities on Day 61
Time Frame: At Day 61
The percentage of participants having hematology and biochemistry results below or above the laboratory normal ranges are tabulated by time point.
Secondary Outcomes
- Number of participants reporting unsolicited AEs from Dose 1 to end of study (Month 18)(From Dose 1 (Day 1) to end of study (Month 18))
- Number of participants reporting MAEs from Dose 1 to end of study (Month 18)(From Dose 1 (Day 1) to end of study (Month 18))
- Number of participants reporting SAEs from Dose 1 to end of study (Month 18)(From Dose 1 (Day 1) to end of study (Month 18))
- Number of participants reporting potential immune-mediated disease (pIMDs) from Dose 1 to end of study (Month 18)(From Dose 1 (Day 1) to end of study (Month 18))
- Neutralizing antibodies (nAbs) titers against epithelial cell infection(On the day of each dose (Day 1, Day 61, Day 181), 30 days post each dose (Day 31, Day 91 and Day 211), 6- and 12-months post-Dose 3 (Day 361, Day 546))
- Anti-pentamer immunoglobulin G (IgG) and anti-gB IgG concentrations(On the day of each dose (Day 1, Day 61, Day 181), 30 days post each dose (Day 31, Day 91 and Day 211), 6- and 12-months post-Dose 3 (Day 361, Day 546))