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
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 333
- 试验地点
- 18
- 主要终点
- Number of participants reporting hematological and biochemical laboratory abnormalities on Day 1
研究概览
简要总结
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 is conducted in healthy adults 18 to 50 years of age, in which the 4 dose levels of the vaccine are administered in a step-wise dose escalation manner, based upon safety adjudication.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Placebo Group
Participants received a dose of placebo at Day 1, Day 61 and Day 181 intramuscularly.
干预措施: Placebo (saline solution) (Combination Product)
Pentamer (low dose)/glycoprotein B (gB) (low dose)/Adjuvant group
Participants received a dose of the candidate cytomegalovirus (CMV) vaccine consisting of a combination of low dose of pentamer and low dose of gB antigens, adjuvanted, at Day 1, Day 61 and Day 181 intramuscularly.
干预措施: Pentamer (low)/gB(low)/Adjuvant vaccine (Biological)
Pentamer (medium dose)/gB (low dose)/Adjuvant group
Participants received a dose of the candidate CMV vaccine consisting of a combination of medium dose of pentamer and low dose of gB antigens, adjuvanted, at Day 1, Day 61 and Day 181 intramuscularly.
干预措施: Pentamer (med)/gB(low)/Adjuvant vaccine (Biological)
Pentamer (medium dose)/gB (medium dose)/Adjuvant group
Participants received a dose of the candidate CMV vaccine consisting of a combination of medium dose of pentamer and medium dose of gB antigens, adjuvanted, at Day 1, Day 61 and Day 181 intramuscularly.
干预措施: Pentamer (med)/gB(med)/Adjuvant vaccine (Biological)
Pentamer (high dose)/gB (medium dose)/Adjuvant group
Participants received a dose of the candidate CMV vaccine consisting of a combination of high dose of pentamer and medium dose of gB antigens, adjuvanted, at Day 1, Day 61 and Day 181 intramuscularly.
干预措施: Pentamer (high)/gB(med)/Adjuvant vaccine (Biological)
结局指标
主要结局
Number of participants reporting hematological and biochemical laboratory abnormalities on Day 1
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: At Day 61
The percentage of participants having hematology and biochemistry results below or above the laboratory normal ranges are tabulated by time point.
Number of Participants With Solicited Administration Site Adverse Events Post Each Dose Administration
时间窗: Within 7 days post each dose (doses administered on Day 1, Day 61 and Day 181)
The assessed solicited administration site adverse events were erythema (injection site redness), pain and swelling.
Number of Participants With Solicited Systemic Adverse Events Post Each Dose Administration
时间窗: Within 7 days post each dose (doses administered on Day 1, Day 61 and Day 181)
The assessed solicited administration site adverse events were arthralgia, fatigue, headache, fever and myalgia. Fever was defined as body temperature ≥38.0°Celsius/100.4°Fahrenheit.
Number of Participants With Unsolicited Adverse Events (AEs) Within 7 Days Post Each Dose Administration
时间窗: Within 7 days post each dose (doses administered on Day 1, Day 61 and Day 181)
An unsolicited AE is defined as an AE that was not included in a list of solicited events using a Participant Diary. Unsolicited AEs include both serious and non-serious AEs.
Number of Participants With Unsolicited Serious Adverse Events (SAEs) Within 7 Days Post Each Dose Administration
时间窗: Within 7 days post each dose (doses administered on Day 1, Day 61 and Day 181)
An SAE is defined as any untoward medical occurrence that, at any dose, resulted in death, was life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity, caused a congenital anomaly/birth defect, or was any other situation identified according to medical or scientific judgment. An unsolicited SAE is defined as an SAE that was not included in a list of solicited events using a Participant Diary.
Number of Participants With Hematological and Biochemical Laboratory Abnormalities on Day 61
时间窗: On Day 61
The hematological and biochemical parameters included ALT, AST, creatinine, eosinophils, hemoglobin, lymphocytes, neutrophils, platelets, WBC. Categories reported when comparing normal range and Day 61 hematological and biochemical laboratory results are defined as follows: \<parameter\>, \<range at timing\> (e.g. Hemoglobin, Below). Below = value below the laboratory reference range defined for the specified visit and laboratory parameter; Within = value within the laboratory reference range defined for the specified visit and laboratory parameter; Above = value above the laboratory reference range defined for the specified visit and laboratory parameter. Missing = No results are available for the corresponding laboratory parameter at the specific timepoint.
Number of Participants With Unsolicited AEs up to 30 Days Post Each Dose Administration
时间窗: Within 30 days post each dose (doses administered on Day 1, Day 61 and Day 181)
An unsolicited AE is defined as an AE that was not included in a list of solicited events using a Participant Diary. The solicited AEs that had an onset after 7 days post each dose administration are considered unsolicited AEs. Unsolicited AEs include both serious and non-serious AEs.
Number of Participants With Unsolicited SAEs up to 30 Days Post Each Dose Administration
时间窗: Within 30 days post each dose (doses administered on Day 1, Day 61 and Day 181)
Number of Participants With Medically Attended Events (MAEs) up to 30 Days Post Each Dose Administration
时间窗: Within 30 days post each dose (doses administered on Day 1, Day 61 and Day 181)
MAE is defined as an AE for which the participant received medical attention defined as hospitalization, an emergency room visit or a visit to or from medical personnel (i.e., nurse practitioner or physician assistant or medical doctor) for any reason.
Number of Participants With Hematological and Biochemical Laboratory Abnormalities on Day 1
时间窗: On Day 1
The hematological and biochemical parameters included alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine, eosinophils, hemoglobin, lymphocytes, neutrophils, platelets, white blood cells (WBC). Categories reported when comparing normal range and Day 1 hematological and biochemical laboratory results are defined as follows: \<parameter\>, \<range at timing\> (e.g. Hemoglobin, Below). Below = value below the laboratory reference range defined for the specified visit and laboratory parameter; Within = value within the laboratory reference range defined for the specified visit and laboratory parameter; Above = value above the laboratory reference range defined for the specified visit and laboratory parameter. Missing = No results are available for the corresponding laboratory parameter at the specific timepoint.
Number of Participants With Hematological and Biochemical Laboratory Abnormalities on Day 8
时间窗: On Day 8
The hematological and biochemical parameters included ALT, AST, creatinine, eosinophils, hemoglobin, lymphocytes, neutrophils, platelets, WBC. Categories reported when comparing normal range and Day 8 hematological and biochemical laboratory results are defined as follows: \<parameter\>, \<range at timing\> (e.g. Hemoglobin, Below). Below = value below the laboratory reference range defined for the specified visit and laboratory parameter; Within = value within the laboratory reference range defined for the specified visit and laboratory parameter; Above = value above the laboratory reference range defined for the specified visit and laboratory parameter. Missing = No results are available for the corresponding laboratory parameter at the specific timepoint.
Number of Participants With Hematological and Biochemical Laboratory Abnormalities on Day 68
时间窗: On Day 68
The hematological and biochemical parameters included ALT, AST, creatinine, eosinophils, hemoglobin, lymphocytes, neutrophils, platelets, WBC. Categories reported when comparing normal range and Day 68 hematological and biochemical laboratory results are defined as follows: \<parameter\>, \<range at timing\> (e.g. Hemoglobin, Below). Below = value below the laboratory reference range defined for the specified visit and laboratory parameter; Within = value within the laboratory reference range defined for the specified visit and laboratory parameter; Above = value above the laboratory reference range defined for the specified visit and laboratory parameter. Missing = No results are available for the corresponding laboratory parameter at the specific timepoint.
Number of Participants With Hematological and Biochemical Laboratory Abnormalities on Day 181
时间窗: On Day 181
The hematological and biochemical parameters included ALT, AST, creatinine, eosinophils, hemoglobin, lymphocytes, neutrophils, platelets, WBC. Categories reported when comparing normal range and Day 181 hematological and biochemical laboratory results are defined as follows: \<parameter\>, \<range at timing\> (e.g. Hemoglobin, Below). Below = value below the laboratory reference range defined for the specified visit and laboratory parameter; Within = value within the laboratory reference range defined for the specified visit and laboratory parameter; Above = value above the laboratory reference range defined for the specified visit and laboratory parameter. Missing = No results are available for the corresponding laboratory parameter at the specific timepoint.
Number of Participants With Hematological and Biochemical Laboratory Abnormalities on Day 188
时间窗: On Day 188
The hematological and biochemical parameters included ALT, AST, creatinine, eosinophils, hemoglobin, lymphocytes, neutrophils, platelets, WBC. Categories reported when comparing normal range and Day 188 hematological and biochemical laboratory results are defined as follows: \<parameter\>, \<range at timing\> (e.g. Hemoglobin, Below). Below = value below the laboratory reference range defined for the specified visit and laboratory parameter; Within = value within the laboratory reference range defined for the specified visit and laboratory parameter; Above = value above the laboratory reference range defined for the specified visit and laboratory parameter. Missing = No results are available for the corresponding laboratory parameter at the specific timepoint.
次要结局
- 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))
- GMT of nAbs Against Epithelial Cell Infection (CMV Status: Sero-negative)(On Day 1, Day 31, Day 61, Day 91, Day 181, Day 211, Day 361 and Day 546)
- Number of Participants With Unsolicited Events, SAEs, MAEs and Potential Immune Mediated Diseases (pIMDs) From Day 1 to Day 546 (End of Study)(Day 1 to Day 546)
- Geometric Mean Titers (GMT) of Neutralizing Antibodies (nAbs) Against Epithelial Cell Infection (CMV Status: Sero-positive)(On Day 1, Day 31, Day 61, Day 91, Day 181, Day 211, Day 361 and Day 546)
- Geometric Mean Concentration (GMC) of Anti-pentamer Immunoglobulin G (IgG) (CMV Serostaus: Sero-positive)(On Day 1, Day 31, Day 61, Day 91, Day 181, Day 211, Day 361 and Day 546)
- GMC of Anti-pentamer IgG (CMV Serostatus: Sero-negative)(On Day 1, Day 31, Day 61, Day 91, Day 181, Day 211, Day 361 and Day 546)
- GMC of Anti-glycoprotein B (gB) IgG (CMV Serostaus: Sero-positive)(On Day 1, Day 31, Day 61, Day 91, Day 181, Day 211, Day 361 and Day 546)
- GMC of Anti-gB IgG (CMV Serostatus: Sero-negative)(On Day 1, Day 31, Day 61, Day 91, Day 181, Day 211, Day 361 and Day 546)