A Study of Safety and Immune Response to Different Doses of a Cytomegalovirus Vaccine in Healthy Adults

Sponsor

GlaxoSmithKline (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05089630

Collaborator

(none)

320

Enrollment

Locations

Arms

37.4

Anticipated Duration (Months)

21.3

Patients Per Site

0.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to assess the safety, reactogenicity and immunogenicity 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.

Condition or Disease	Intervention/Treatment	Phase
Cytomegalovirus Infections	Biological: Pentamer (low)/gB(low)/Adjuvant vaccine Biological: Pentamer (med)/gB(low)/Adjuvant vaccine Biological: Pentamer (med)/gB(med)/Adjuvant vaccine Biological: Pentamer (high)/gB(med)/Adjuvant vaccine Drug: Placebo (saline)	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

320 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Prevention

Official Title:

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

Actual Study Start Date :

Oct 14, 2021

Anticipated Primary Completion Date :

Aug 14, 2023

Anticipated Study Completion Date :

Nov 25, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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 the study end (Day 546).	Biological: Pentamer (low)/gB(low)/Adjuvant vaccine Three doses of the candidate CMVsu vaccine consisting of a combination of low dose pentamer and low dose gB antigens, adjuvanted are administered intramuscularly in the deltoid region of the non-dominant arm in a 0, 2, 6-month schedule.
Experimental: 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 the study end (Day 546).	Biological: Pentamer (med)/gB(low)/Adjuvant vaccine Three doses of the candidate CMVsu vaccine consisting of a combination of medium dose pentamer and low dose gB antigens, adjuvanted are administered intramuscularly in the deltoid region of the non-dominant arm in a 0, 2, 6-month schedule.
Experimental: 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 the study end (Day 546).	Biological: Pentamer (med)/gB(med)/Adjuvant vaccine Three doses of the candidate CMVsu vaccine consisting of a combination of medium dose pentamer and medium dose gB antigens, adjuvanted are administered intramuscularly in the deltoid region of the non-dominant arm in a 0, 2, 6-month schedule.
Experimental: 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 the study end (Day 546).	Biological: Pentamer (high)/gB(med)/Adjuvant vaccine Three doses of the candidate CMVsu vaccine consisting of a combination of high dose pentamer and medium dose gB antigens, adjuvanted are administered intramuscularly in the deltoid region of the non-dominant arm in a 0, 2, 6-month schedule.
Placebo Comparator: Placebo Group Participants receive placebo (saline) at 0, 2 and 6 months and are followed up until the study end (Day 546).	Drug: Placebo (saline) Three doses of placebo (saline) are administered intramuscularly in the deltoid region of the non-dominant arm in a 0, 2, 6-month schedule.

Outcome Measures

Primary Outcome Measures

Number of participants reporting solicited administration site events [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 solicited systemic events [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 [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 [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 unsolicited AEs up to 30 days after each dose [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 SAEs up to 30 days after each dose [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 medically attended AEs (MAEs) up to 30 days after each dose [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 1 [At Day 1]
The number 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 8 [At Day 8]
The number 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 61 [At Day 61]
The number 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 68 [At Day 68]
The number 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 [At Day 181]
The number 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 [Day 188]
The number of participants having hematology and biochemistry results below or above the laboratory normal ranges are tabulated by time point.

Secondary Outcome Measures

Number of participants reporting unsolicited AEs from Dose 1 to end of study [From Dose 1 (Day 1) to end of study (Day 546)]
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 MAEs from Dose 1 to end of study [From Dose 1 (Day 1) to end of study (Day 546)]
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 SAEs from Dose 1 to end of study [From Dose 1 (Day 1) to end of study (Day 546)]
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 potential immune-mediated disease (pIMDs) from Dose 1 to end of study [From Dose 1 (Day 1) to end of study (Day 546)]
PIMDs include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune etiology.
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)]
The humoral immune response is measured in terms of nAbs against epithelial cell infection and expressed as geometric mean titers (GMT). Serological assays for the determination of antibodies against CMV are performed by neutralization assay.
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)]
The vaccine-induced anti-gB and anti-pentamer humoral immune response is measured in terms of anti-pentamer IgG and anti-gB IgG geometric mean concentrations (GMCs) determined by enzyme linked immunosorbent assay (ELISA) and expressed in EU/ml.
CMV specific cluster of differentiation (CD)4+ T-cells frequency [Before each dose (Day 1, Day 61, Day 181), 1-month post-dose 2 and dose 3 (Day 91, Day 211), 6- and 12-months post-dose 3 (Day 361, Day 546)]
The vaccine-induced cellular immune response is measured in terms of CD4+ T-cells frequency per million PBMCs.
CMV specific CD8+ T-cells frequency [Before each dose (Day 1, Day 61, Day 181), 1-month post-dose 2 and dose 3 (Day 91, Day 211), 6- and 12-months post-dose 3 (Day 361, Day 546)]
The vaccine-induced cellular immune response is measured in terms of cytokine expressing CD4+ T-cells per million PBMCs.
Anti-CMV IgG antibody concentration [At screening (Day -29) and 1-month post-dose 1 and 2 (Day 31, Day 91)]
The clinical performance is measured in terms of anti-CMV IgG antibody concentration obtained with a serodiagnostic kit / commercial CMV lysate i.e. (LIAISON® CMV IgG - chemoluminescent immuno assay [CLIA] assay) and expressed as GMCs
Number of concordant CMV sero-status results [At screening (Day -29)]
The number of concordant CMV sero-status results (positive/negative) obtained with both assays will be assessed at screening visit (Day -29).

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 50 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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.
Participants who initially fail screening due to COVID-19 infection may be re-screened and included in the study, within the screening window period.
Participants who are diagnosed with COVID-19 may receive their subsequent CMVsu vaccination dose provided they have no fever, and their condition is considered stable by the investigator (e.g. there may be mild lingering cough, but no shortness of breath or difficulty breathing) within 30 days of the original schedule.
Participants who initially fail screening due to other active infections may be re screened within the screening window period and included in the study, if they no longer have signs or symptoms of active infection in the judgment of the site investigator.
If a participant has equivocal results on CMV diagnostic ELISA screening, they are permitted to be re-screened if within the 28-day screening window. Flexibility in safety blood evaluations will be permitted within the Schedule of activities time intervals.

Exclusion Criteria:

Medical conditions

Known documented medical history of human immunodeficiency virus 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, based on medical history and physical examination.
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, as assessed by the investigator.
Acute or chronic clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by physical examination or laboratory screening tests.
Recurrent history or uncontrolled neurological disorders.
Any hematological or biochemical abnormality*.
*Participants with Food and Drug Administration (FDA) toxicity Grade 1 differential cell counts and considered not clinically significant may be enrolled at the discretion of the investigator, and with the review and approval of the medical monitor.
Participants with hematological / biochemical values out of normal range which are not clinically significant and expected to be temporary may be re-screened within the allowed window period.
Any acute or chronic, clinically significant disease, as determined by physical examination or laboratory screening tests.
Any medical condition that in the judgment of the investigator would make intramuscular injection unsafe.
Participants with symptoms suggestive of active COVID-19 infection are excluded.
Participants with known COVID-19 positive contacts within the past 14 days should be excluded for at least 14 days since the exposure and the participant remains symptom free.
Any other clinical condition that, in the opinion of the investigator, might pose additional risk to the participant due to participation in the study.

Prior/Concomitant therapy

Any history of or planned receipt of a CMV vaccine other than the study intervention (CMVsu) at any time point.
Use of other investigational or non-registered product during the period beginning 30 days before the first dose, or their planned use during the study period.
Planned administration or administration of any vaccine not foreseen by the study protocol 30 days before and 30 days after each study vaccination administration, with the exception of any licensed influenza vaccine which may be administered > 15 days before or after vaccination.
In case of emergency mass vaccination for an unforeseen public health threat) organized by public health authorities outside the routine immunization program, the time period can be reduced if necessary, for that mass vaccination vaccine, which may be under emergency use authorization.
COVID-19 vaccines should be given at least 30 days before or after administration of a GSK study vaccine. However, this interval can be reduced to > 14 days, if emergency vaccination is recommended by public health authorities, in line with the applicable local/national guidance per COVID-19 vaccine platform type under emergency use authorization.
Candidate COVID-19 vaccines that have not received limited, accelerated, or full authorization, and are only in use as part of a clinical trial, are not allowed.
Chronic administration of immunosuppressants or other immune-modifying drugs within 3 months prior to the vaccine dose. Inhaled and topical steroids are allowed.
Administration of long-acting immune-modifying drugs at any time during the study period.
Administration of immunoglobulins and/or any blood products during the period starting 3 months before the administration of the first dose of study intervention(s) or planned administration during the study period.

Prior/Concurrent clinical study experience

• Concurrently participating in another clinical study, at any time during the study period, in which the participant has been or will be exposed to an investigational or a non-investigational intervention

Other exclusions

Pregnant or lactating women. If a woman becomes pregnant/lactating during the study, she will be excluded from subsequent vaccine doses but will be followed for safety.
Women planning to become pregnant or planning to discontinue contraceptive precautions before 3 months after last study vaccination.
Participants with known high exposure risk for CMV transmission, to enable distinction of true vaccine effect from natural infection during the study.
Planned move to a location that will prohibit participating in the trial until study end.
Participants with current chronic alcohol consumption and/or drug abuse as defined by Diagnostic and Statistical Manual of Mental Disorders 5th edition.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Long Beach	California	United States	90806
2	GSK Investigational Site	Los Angeles	California	United States	90017
3	GSK Investigational Site	Hallandale Beach	Florida	United States	33009
4	GSK Investigational Site	Hollywood	Florida	United States	33024
5	GSK Investigational Site	Miami	Florida	United States	33143
6	GSK Investigational Site	Lenexa	Kansas	United States	66219
7	GSK Investigational Site	Lexington	Kentucky	United States	40536-0084
8	GSK Investigational Site	Dearborn	Michigan	United States	48124
9	GSK Investigational Site	Springfield	Missouri	United States	65802
10	GSK Investigational Site	Lincoln	Nebraska	United States	68510
11	GSK Investigational Site	Omaha	Nebraska	United States	68134
12	GSK Investigational Site	Las Vegas	Nevada	United States	89109
13	GSK Investigational Site	Austin	Texas	United States	78705
14	GSK Investigational Site	Cedar Park	Texas	United States	78613
15	GSK Investigational Site	League City	Texas	United States	77573