A Phase 3, Randomized, Controlled, Partially Blind, Immuno-bridging Study to Evaluate Immunogenicity, Reactogenicity, Safety and the Occurrence of RSV Associated Respiratory Tract Illness After Administration of a Single Dose of GSK's RSVPreF3 OA Investigational Vaccine in Adults Aged 60 Years and Older
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 2,620
- 试验地点
- 39
- 主要终点
- RSV-A neutralization titers expressed as geometric mean titers (GMTs) in RSV OA vaccine Group (Overseas) and RSV OA vaccine Group (China), and between-group GMT ratios
研究概览
简要总结
The purpose of the current study is to evaluate the immune response of the RSVPreF3 OA investigational vaccine in older adults (OA) at least (>=) 60 years of age (YOA) in China compared to OA in the same age range to be enrolled from overseas countries that participated in the RSV OA=ADJ-006 (NCT04886596) study, since the vaccine efficacy against lower respiratory tract disease (LRTD) has been demonstrated following a single dose of the RSVPreF3 OA investigational vaccine in the global efficacy study RSV OA=ADJ-006. In addition, the safety (in all participants) , reactogenicity and occurrence of RSV-associated acute respiratory illness (ARI) (in study participants in China only) after administration of the vaccine are also assessed in the current study. No ARI surveillance will be conducted for the overseas participants.
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)
盲法说明
Data from study participants in China is collected in an observer-blind manner. The study is open labelled for overseas participants.
入排标准
- 年龄范围
- 60 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Adult male or female of ≥60 YOA at the time of study intervention administration, who live in the community dwelling (CD participants).
- •Participants who, in the opinion of the investigator, can and will comply with the requirements of the protocol (e.g., completion of the diary cards, attend regular phone calls/study site visits, perform self-swabbing (study participants in China only), ability to access and utilize a phone or other electronic communications).
- •Participants who are medically stable in the opinion of the investigator at the time of vaccination. Participants with chronic stable medical conditions with or without specific treatment, such as diabetes, hypertension or cardiac disease, are allowed to participate in this study if considered by the investigator as medically stable.
- •Written or witnessed informed consent obtained from the participant (participant must be able to understand the informed consent) prior to performance of any study specific procedure.
排除标准
- •Medical Conditions:
- •History of any reaction or hypersensitivity likely to be exacerbated by any component of the study intervention(s).
- •Any clinical conditions for which serum samples would be prohibited for transfer to local central lab for testing. These clinical conditions include hepatitis B, hepatitis C, HIV and Syphilis based on medical history and physical examination (all participants) and laboratory screening tests (overseas participants).
- •Any confirmed or suspected immunosuppressive or immunodeficient condition resulting from disease (e.g., current malignancy, human immunodeficiency virus) or immunosuppressive/cytotoxic therapy (e.g., medication used during cancer chemotherapy, organ transplantation, or to treat autoimmune disorders), based on medical history and physical examination (no laboratory testing required).
- •Any history of dementia or any medical condition that moderately or severely impairs cognition.
- •Recurrent history or uncontrolled neurological disorders or seizures. Participants with medically controlled active or chronic neurological diseases can be enrolled in the study as per investigator assessment, provided that their condition will allow them to comply with the requirements of the protocol (e.g. completion of the diary cards, attend regular phone calls/study site visits, perform self-swabbing (study participants in China only).
- •Significant underlying illness that in the opinion of the investigator would be expected to prevent completion of the study (e.g., life-threatening disease likely to limit survival to less than 1 year).
- •Serious or unstable chronic illness.
- •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:
- •Previous vaccination with RSV vaccine.
- •Use of any investigational or non-registered product (drug, vaccine or invasive medical device) other than the study intervention(s) during the period beginning 30 days before the dose of study intervention(s), or their planned use during the study period.
- •Planned or actual administration of a vaccine not foreseen by the study protocol in the period starting 30 days before and ending 30 days after study intervention administration, with the exception of COVID-19 and inactivated/subunit influenza vaccines which can be administered up to 14 days before or from 14 days after each study intervention.
- •Administration of long-acting immune-modifying drugs or planned administration at any time during the study period (e.g., infliximab).
- •Administration of immunoglobulins and/or any blood products or plasma derivatives during the period starting 90 days before the study intervention administration or planned administration during the study period.
- •Chronic administration (defined as more than 14 consecutive days in total) of immunosuppressants or other immune-modifying drugs during the period starting 90 days prior to the study intervention administration or planned administration during the study period. For corticosteroids, this will mean prednisone >=20 mg/day, or equivalent. Inhaled and topical steroids are allowed.
- •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 (drug/invasive medical device).
- •Other Exclusion Criteria:
- •History of chronic alcohol consumption and/or drug abuse as deemed by the investigator to render the potential participant unable/unlikely to provide accurate safety reports or comply with study procedures.
- •Bedridden participants.
- •Planned move during the study conduct that prohibits participation until study end.
- •Participation of any study personnel or their immediate dependents, family, or household members.
研究组 & 干预措施
RSV OA vaccine Group (China)
Chinese OA participants received a single dose of RSVPreF3 OA investigational vaccine at Day 1 and were followed up until end of study (Month 6 or last acute respiratory illness (ARI) visit/contact, whichever was later).
干预措施: RSVPreF3 OA investigational vaccine (Biological)
RSV OA vaccine Group (Overseas)
Overseas older adults (OA) participants received a single dose of RSVPreF3 OA investigational vaccine at Day 1 and were followed up until end of study (Month 6).
干预措施: RSVPreF3 OA investigational vaccine (Biological)
Placebo Group (China)
Chinese OA participants received a single dose of placebo at Day 1 and were followed up until end of study (Month 6 or last ARI visit/contact, whichever was later).
干预措施: Placebo (Saline solution) (Drug)
结局指标
主要结局
RSV-A neutralization titers expressed as geometric mean titers (GMTs) in RSV OA vaccine Group (Overseas) and RSV OA vaccine Group (China), and between-group GMT ratios
时间窗: At 1 month after the RSVPreF3 OA investigational vaccine administration (Day 31)
RSV-A neutralization titers are determined by neutralization assay and expressed as GMTs.
Percentage of participants showing group seroresponse for RSV-A in RSV OA vaccine Group (Overseas) and RSV OA vaccine Group (China), and between-group differences
时间窗: At 1 month after the RSVPreF3 OA investigational vaccine administration (Day 31)
A participant with seroresponse for RSV-A is defined as a participant having at least a 4-fold increase in RSV-A neutralizing titers (1 month post-study intervention administration over pre-study intervention administration \>=4).
RSV-B neutralization titers expressed as geometric mean titers (GMTs) in RSV OA vaccine Group (Overseas) and RSV OA vaccine Group (China), and between-group GMT ratios)
时间窗: At 1 month after the RSVPreF3 OA investigational vaccine administration (Day 31)
RSV-B neutralization titers are determined by neutralization assay and expressed as GMTs.
Percentage of participants showing group seroresponse for RSV-B in RSV OA vaccine Group (Overseas) and RSV OA vaccine Group (China), and between-group differences
时间窗: At 1 month after the RSVPreF3 OA investigational vaccine administration (Day 31)
A participant with seroresponse for RSV-B is defined as a participant having at least a 4-fold increase in RSV-B neutralizing titers (1 month post-study intervention administration over pre-study intervention administration \>=4).
RSV-A Neutralizing Titers Expressed as Adjusted Geometric Mean Titers (GMTs) at 1 Month Post RSVPreF3 OA Vaccination
时间窗: At Day 31
RSV-A neutralizing titers were determined by neutralization assay and the results were expressed as GMTs. Adjusted GMTs are derived using an ANCOVA model on log10-transformed titers for the neutralization assay. The final ANCOVA model includes treatment group as fixed effect, and the pre-dose log10-transformed titers as a covariate.
Percentage of Participants With Seroresponse for RSV-A Neutralizing Titers at 1 Month Post RSVPreF3 OA Vaccination
时间窗: At Day 31 compared to baseline (Day 1)
Seroresponse was defined as at least a 4 fold (≥4) increase in neutralizing titers (1 month post-study intervention administration over pre-study intervention administration).
RSV-B Neutralizing Titers Expressed as Adjusted GMTs at 1 Month Post RSVPreF3 OA Vaccination
时间窗: At Day 31
RSV-B neutralizing titers were determined by neutralization assay and the results were expressed as GMTs. Adjusted GMTs are derived using an ANCOVA model on log10-transformed titers for the neutralization assay. The final ANCOVA model includes treatment group as fixed effect, and the pre-dose log10-transformed titers as a covariate.
Percentage of Participants With Seroresponse for RSV-B Neutralizing Titers at 1 Month Post RSVPreF3 OA Vaccination
时间窗: At Day 31 compared to baseline (Day 1)
次要结局
- RSV-A neutralization titers expressed as group GMTs in the immunogenicity subset of RSV OA=ADJ-006 study and in RSV OA vaccine Group (China)(At 1 month after the RSVPreF3 OA investigational vaccine administration (Day 31))
- Percentage of participants showing seroresponse for RSV-B in the immunogenicity subset of RSV OA=ADJ-006 study and in RSV OA vaccine Group (China)(At 1 month after the RSVPreF3 OA investigational vaccine administration (Day 31))
- Number of participants with solicited administration site events in RSV OA Group (China) and Placebo Group (China)(Within 7 days after study intervention administration (the day of study intervention administration and the subsequent 6 days))
- Number of participants with serious adverse events (SAEs) in all study groups(From the study intervention administration (Day 1) to Month 6)
- Percentage of participants showing seroresponse for RSV-A in RSV OA vaccine Group (Overseas) and RSV OA vaccine Group (China)(At 1 month (Day 31) and at 6 months (Day 181) after the RSVPreF3 OA investigational vaccine administration)
- RSV-A neutralization titers expressed as GMTs in RSV OA vaccine Group (Overseas) and RSV OA vaccine Group (China)(At Baseline (Day 1), at 1 month (Day 31) and at 6 months (Day 181) after the RSVPreF3 OA investigational vaccine administration)
- RSV-B neutralization titers expressed as group GMTs in the immunogenicity subset of RSV OA=ADJ-006 study and in RSV OA vaccine Group (China)(At 1 month after the RSVPreF3 OA investigational vaccine administration (Day 31))
- Number of participants with pIMDs related to study interventions in all study groups(From the RSVPreF3 OA investigational vaccine administration (Day 1) to study end (approximately 6 months post dose administration))
- Percentage of participants showing seroresponse for RSV-B in RSV OA vaccine Group (Overseas) and RSV OA vaccine Group (China)(At 1 month (Day 31) and at 6 months (Day 181) after the RSVPreF3 OA investigational vaccine administration)
- Percentage of participants showing seroresponse for RSV-A in the immunogenicity subset of RSV OA=ADJ-006 study and in RSV OA vaccine Group (China)(At 1 month after the RSVPreF3 OA investigational vaccine administration (Day 31))
- Number of participants with real time polymerase chain reaction (RT-PCR) confirmed RSV-A associated ARI and LRTD in RSV OA vaccine Group (China) and Placebo Group (China)(From the RSVPreF3 OA investigational vaccine administration (Day 1) to Month 6)
- Number of participants with RT-PCR confirmed RSV-B associated ARI and LRTD RSV OA vaccine Group (China) and Placebo Group (China)(From the RSVPreF3 OA investigational vaccine administration (Day 1) to Month 6)
- Number of participants with solicited systemic events in RSV OA Group (China) and Placebo Group (China)(Within 7 days after study interventions (the day of study intervention administration and the subsequent 6 days))
- Number of participants with unsolicited adverse events (AEs) in RSV OA Group (China) and Placebo Group (China)(Within 30 days after study interventions (the day of study intervention administration and the subsequent 29 days))
- Number of participants with any fatal SAEs in all study groups(From the RSVPreF3 OA investigational vaccine administration (Day 1) to study end (approximately 6 months post dose administration))
- RSV-B neutralization titres expressed as GMTs in RSV OA vaccine Group (Overseas) and RSV OA vaccine Group (China)(At Baseline (Day 1), at 1 month (Day 31) and at 6 months (Day 181) after the RSVPreF3 OA investigational vaccine administration)
- Number of participants with potential immune-mediated disease (pIMDs) in all study groups(From the study intervention administration (Day 1) to Month 6)
- Number of participants with SAEs related to study intervention in all study groups(From the study intervention administration (Day 1) to study end (approximately 6 months post dose administration))
- Number of Participants With RSV-confirmed ARI and LRTD Episodes by Severity(From Day 15 and up to study end (6 months post dose [dose administered at Day 1]))
- RSV-A Neutralizing Titers Expressed as Unadjusted GMTs at Baseline and 1 Month Post RSVPreF3 OA Vaccination(At Day 1 (baseline) and Day 31 (1 month post RSVPreF3 OA vaccination))
- RSV-B Neutralizing Titers Expressed as Unadjusted GMTs at Baseline and 1 Month Post RSVPreF3 OA Vaccination(At Day 1 (baseline) and Day 31 (1 month post RSVPreF3 OA vaccination))
- RSV-A and RSV-B Neutralizing Titers Expressed as Unadjusted GMTs at 6 Months Post RSVPreF3 OA Vaccination(At Day 181 (6 months post RSVPreF3 OA vaccination))
- Percentage of Participants With Seroresponse for RSV-A and RSV-B Neutralizing Titers at 1 Month Post RSVPreF3 OA Vaccination(At Day 31 compared to baseline (Day 1))
- Percentage of Participants With Seroresponse for RSV-A and RSV-B Neutralizing Titers at 6 Months Post RSVPreF3 OA Vaccination(At Day 181 compared to baseline (Day 1))
- RSV-A and RSV-B Neutralizing Titers Expressed as Adjusted GMTs at 1 Month Post RSVPreF3 OA Vaccination Between RSV OA Overseas (RSV OA=ADJ-006 Study) vs RSV OA Vaccine Group (China) Group(At Day 31)
- Percentage of Participants With Seroresponse for RSV-A and RSV-B Neutralizing Titers at 1 Month Post RSVPreF3 OA Vaccination Between RSV OA Overseas (RSV OA=ADJ-006 Study) vs RSV OA Vaccine Group (China) Group(At Day 31 compared to baseline (Day 1))
- Number of Participants With Real Time Polymerase Chain Reaction (RT-PCR) Confirmed RSV-A/B Associated Acute Respiratory Illness (ARI) and Lower Respiratory Tract Disease (LRTD) Cases(From Day 15 and up to study end (6 months post dose [dose administered at Day 1]))
- Duration of Episodes for RSV-confirmed ARI and LRTD Cases(From Day 15 and up to study end (6 months post dose [dose administered at Day 1]))
- Number of Episodes of Each of the Symptoms/Signs Associated to RSV-confirmed ARI Cases(From Day 15 and up to study end (6 months post dose [dose administered at Day 1]))
- Number of Episodes of Each of the Symptoms/Signs Associated With RSV-confirmed LRTD Cases(From Day 15 and up to study end (6 months post dose [dose administered at Day 1]))
- Number of Participants With RSV-confirmed ARI and LRTD Cases by Frailty Status(From Day 15 and up to study end (6 months post dose [dose administered at Day 1]))
- Number of Participants Reporting Any Solicited Administration Site Adverse Events(Day 1 (baseline) to Day 7)
- Number of Participants Reporting Any Solicited Systemic Adverse Events(Day 1 (baseline) to Day 7)
- Number of Participants Reporting Any Unsolicited Adverse Events (AEs)(Day 1 (baseline) to Day 30)
- Number of Participants Reporting Any Serious Adverse Events (SAEs), Related SAEs and Fatal SAEs up to Data Lock Point of Primary Analysis(Day 1 (baseline) up to data lock point of primary analysis (median follow-up: 229 days [min.: 28 days, max.: 338 days))
- Number of Participants Reporting Any SAEs, Related SAEs and Fatal SAEs up to End of Study(Throughout the study period (up to 6 months post dose [administered at Day 1 (baseline)]))
- Number of Participants Reporting Any Potential Immune-mediated Disease (pIMDs) and Related pIMDs up to Data Lock Point for Primary Analysis(Day 1 (baseline) up to data lock point of primary analysis (median follow-up: 229 days [min.: 28 days, max.: 338 days))
- Number of Participants Reporting Any pIMDs and Related pIMDs up to End of Study(Throughout the study period (up to 6 months post dose [administered at Day 1 (baseline)]))