Clinical trial NCT05089630: A Study of Safety and Immune Response to Different Doses of a Cytomegalovirus Vaccine in Healthy Adults
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Cytomegalovirus Infections
Keywords: Cytomegalovirus
First-Time-in Human
Safety
Reactogenicity
Immunogenicity
Healthy adults
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2021-10-22
Enrollment: 339
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.


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.
* 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 with signs/symptoms suggestive of active COVID-19 (i.e., fever, cough, etc.) should be isolated for the time period recommended by CDC since the signs/symptoms started, and symptoms have resolved.
* Participants with known COVID-19 positive contacts should be quarantined for the time period since exposure recommended by CDC since the exposure and the participant remains symptom free or COVID test negative.
* 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 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 serodiagnostic screening test, they are permitted to be re-screened if within the 60-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 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.
* Recurrent history or uncontrolled neurological disorders.
* Any hematological or biochemical abnormality.
* Any acute or chronic, clinically significant disease or pulmonary, cardiovascular, hepatic, or renal functional abnormalities.
* 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, 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 at any time point.
* Use of other investigational/non-registered product during the period beginning 30 days before the first dose, or their planned use during the study period.
* Planned administration of any vaccine not foreseen by the study protocol 30 days before and 30 days after each study vaccination administration any licensed influenza vaccine administered \> 15 days before/ after vaccination.
* In case of extraordinary emergency mass vaccination for an unforeseen public health threat 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. This interval can be reduced to \> 14 days, if emergency vaccination is recommended by public health authorities.
  * Candidate COVID-19 vaccines 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.

Primary outcomes:
measure: Number of participants reporting solicited administration site events
timeFrame: Within 7 days (the day of dose and 6 subsequent days) after each dose (vaccines administered on Day 1, Day 61 and Day 181)
measure: Number of participants reporting solicited systemic events
timeFrame: Within 7 days (the day of dose and 6 subsequent days) after each dose (vaccines administered on Day 1, Day 61 and Day 181)
measure: Number of participants reporting unsolicited adverse events (AEs) within 7 days after each dose
timeFrame: Within 7 days (the day of dose and 6 subsequent days) after each dose (vaccines administered on Day 1, Day 61 and Day 181)
measure: Number of participants reporting serious adverse events (SAEs) within 7 days after each dose
timeFrame: Within 7 days (the day of dose and 6 subsequent days) after each dose (vaccines administered on Day 1, Day 61 and Day 181)
measure: Number of participants reporting unsolicited AEs up to 30 days after each dose
timeFrame: Up to 30 days after each dose (vaccines administered on Day 1, Day 61 and Day 181)
measure: Number of participants reporting SAEs up to 30 days after each dose
timeFrame: Up to 30 days after each dose (vaccines administered on Day 1, Day 61 and Day 181)
measure: Number of participants reporting medically attended AEs (MAEs) up to 30 days after each dose
timeFrame: Up to 30 days after each dose (vaccines administered on Day 1, Day 61 and Day 181)
measure: Number of participants reporting hematological and biochemical laboratory abnormalities on Day 1
timeFrame: At Day 1
measure: Number of participants reporting hematological and biochemical laboratory abnormalities on Day 8
timeFrame: At Day 8
measure: Number of participants reporting hematological and biochemical laboratory abnormalities on Day 61
timeFrame: At Day 61
measure: Number of participants reporting hematological and biochemical laboratory abnormalities on Day 68
timeFrame: At Day 68
measure: Number of participants reporting hematological and biochemical laboratory abnormalities on Day 181
timeFrame: At Day 181
measure: Number of participants reporting hematological and biochemical laboratory abnormalities on Day 188
timeFrame: Day 188
Secondary outcomes:
measure: Number of participants reporting unsolicited AEs from Dose 1 to end of study (Month 18)
timeFrame: From Dose 1 (Day 1) to end of study (Month 18)
measure: Number of participants reporting MAEs from Dose 1 to end of study (Month 18)
timeFrame: From Dose 1 (Day 1) to end of study (Month 18)
measure: Number of participants reporting SAEs from Dose 1 to end of study (Month 18)
timeFrame: From Dose 1 (Day 1) to end of study (Month 18)
measure: Number of participants reporting potential immune-mediated disease (pIMDs) from Dose 1 to end of study (Month 18)
timeFrame: From Dose 1 (Day 1) to end of study (Month 18)
measure: Neutralizing antibodies (nAbs) titers against epithelial cell infection
timeFrame: 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)
measure: Anti-pentamer immunoglobulin G (IgG) and anti-gB IgG concentrations
timeFrame: 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)
Other outcomes:
Locations:
city: Anaheim
country: United States
facility: GSK Investigational Site
state: California
city: Long Beach
country: United States
facility: GSK Investigational Site
state: California
city: Los Angeles
country: United States
facility: GSK Investigational Site
state: California
city: Hallandale Beach
country: United States
facility: GSK Investigational Site
state: Florida
city: Miami
country: United States
facility: GSK Investigational Site
state: Florida
city: Lexington
country: United States
facility: GSK Investigational Site
state: Kentucky
city: Dearborn
country: United States
facility: GSK Investigational Site
state: Michigan
city: Springfield
country: United States
facility: GSK Investigational Site
state: Missouri
city: Lincoln
country: United States
facility: GSK Investigational Site
state: Nebraska
city: Omaha
country: United States
facility: GSK Investigational Site
state: Nebraska
city: Las Vegas
country: United States
facility: GSK Investigational Site
state: Nevada
city: Newark
country: United States
facility: GSK Investigational Site
state: New Jersey
city: Secaucus
country: United States
facility: GSK Investigational Site
state: New Jersey
city: New York
country: United States
facility: GSK Investigational Site
state: New York
city: Austin
country: United States
facility: GSK Investigational Site
state: Texas
city: Cedar Park
country: United States
facility: GSK Investigational Site
state: Texas
city: Galveston
country: United States
facility: GSK Investigational Site
state: Texas
city: Puyallup
country: United States
facility: GSK Investigational Site
state: Washington
Study officials:
References: