A PHASE 3 PROTOCOL TO EVALUATE THE SAFETY, TOLERABILITY, AND IMMUNOGENICITY OF RESPIRATORY SYNCYTIAL VIRUS (RSV) PREFUSION F SUBUNIT VACCINE IN ADULTS AT HIGH RISK OF SEVERE RSV DISEASE
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 885
- 试验地点
- 32
- 主要终点
- SSA: Percentage of Participants With Local Reactions Within 7 Days After Vaccination
研究概览
简要总结
The purpose of this study is to learn about the safety and immunogenicity of a study vaccine (called RSVpreF) in several adult groups. Respiratory Syncytial Virus (RSV) is a common type of virus (germ) that can cause severe illness, where medical help is needed. RSV can lead to airway diseases in all ages. Vaccines help your body make antibodies which help fight against diseases. This is called an immune response. This study will measure how much antibody participants make after receiving RSVpreF (immunogenicity).
The study consists of 2 groups (Substudy A and Substudy B).
Substudy A is seeking approximately 675 participants who are:
- Between 18 and 60 years of age.
- Considered having a high likelihood of severe RSV disease due to certain long-term medical conditions. Such medical conditions do not include immunocompromising conditions.
Participants will need to come to the study clinic at least 2 times. At the first clinic visit, participants will receive 1 shot of RSVpreF or placebo in the arm by chance. A placebo looks like the study vaccine but contains no active ingredients. At each clinic visit, a blood sample will be taken. A third (final) visit can be either completed in clinic or via telephone contact. This study is about 6 months long for each participant.
Substudy B is seeking approximately 200 participants who are:
- At least 18 years of age. About half of the participants will be at least 60 years of age.
- Considered having a weakened immune system (immunocompromised). Participants will need to come to the study clinic at least 3 times. All participants will receive a shot of RSVpreF at the first study clinic visit. The second study clinic visit will be 1 month later. All participants will receive a second shot of the study vaccine at this second study clinic visit. Blood samples will be taken at the 3 study clinic visits. A fourth (final) visit can be either completed in clinic or via telephone contact. This study is about 7 months long for each participant.
详细描述
This is a Phase 3 protocol that will assess the safety, tolerability, and immunogenicity of Pfizer's RSVpreF in adults at high risk of severe RSV disease. Each substudy design is detailed separately, and these substudies may be conducted in parallel, as required by the clinical plan, within the framework of this protocol.
Substudy A Design:
This is a Phase 3, multicenter, randomized, double-blinded, placebo-controlled study that will assess the safety, tolerability, and immunogenicity of Pfizer's RSVpreF in adults 18 to <60 years of age considered to be at high risk of RSV disease due to certain chronic medical conditions.
Approximately 675 participants ≥18 to <60 years of age considered at high risk of RSV disease due to certain chronic medical conditions, excluding immunocompromising conditions, will be randomized to receive a single 120-µg dose of RSVpreF or placebo in a 2:1 ratio. Enrollment will be monitored to help ensure distribution of vaccination across the age range. The duration of study participation for each participant will be 6 months, with 3 scheduled visits.
All participants will have blood drawn at baseline prior to vaccination and at 1 month after vaccination to assess immunogenicity. Immunogenicity elicited at 1 month after vaccination with RSVpreF in Substudy A will be bridged to the immunogenicity of participants 60 years of age and older in the C3671013 study, in which RSVpreF efficacy was demonstrated.
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
- Triple (Participant, Care Provider, Investigator)
盲法说明
Substudy A is double blind therefore all parties (participant, site staff and sponsor) will be blinded to study intervention.
Substudy B is open-label therefore no blinding requirements are in place since all participants will receive RSVpreF.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Capable of giving signed informed consent as described per protocol.
- •Participants ≥18 to <60 years of age at study enrollment.
- •Life expectancy ≥12 months (365 days) in the opinion of the investigator at enrollment.
- •Participants who are willing and able to comply with all scheduled visits, vaccination plan, lifestyle considerations, and other study procedures.
- •Participants who are considered at high risk of RSV disease by virtue of the following:
- •Adults with chronic pulmonary (including asthma), cardiovascular (excluding isolated hypertension), renal, hepatic, neurologic, hematologic, or metabolic disorders (including diabetes mellitus).
- •Chronic medical conditions for this substudy are defined as:
- •Duration greater than 6 months.
- •Stable disease not requiring a significant change in therapy in the previous 6 weeks or hospitalization for worsening disease within 12 weeks before receipt of study intervention.
- •Requires regular medical follow-up or ongoing medication or hospitalization in the previous year.
- •Additional groups at high risk include:
- •Residents of nursing homes and other long-term care facilities.
排除标准
- •Bleeding diathesis or condition associated with prolonged bleeding that would, in the opinion of the investigator, contraindicate intramuscular injection.
- •History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (eg, anaphylaxis) to any component of the study intervention(s) or any related vaccine.
- •Participants who do not have adequate deltoid muscle mass to allow intramuscular vaccination, in the opinion of the investigator.
- •Serious chronic disorder, including metastatic malignancy, end-stage renal disease with or without dialysis, clinically unstable cardiac disease, or any other disorder that, in the investigator's opinion, excludes the participant from participating in the study.
- •Immunocompromised individuals with known or suspected immunodeficiency, as determined by history and/or laboratory/physical examination.
- •Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study.
- •Note: Specific criteria for participants with known stable infection with HIV can be found in protocol.
- •Individuals who receive chronic systemic treatment with immunosuppressive therapy, including cytotoxic agents, immunosuppressive monoclonal antibodies, systemic corticosteroids*, eg, for cancer or an autoimmune disease, or radiotherapy, from 60 days before study intervention administration or planned receipt throughout the study.
- •*Applies to systemic corticosteroids administered for ≥14 days at a dose of ≥20 mg/day of prednisone or equivalent (eg, for cancer or an autoimmune disease). Systemic corticosteroids administered at a dose of <20 mg/day of prednisone or equivalent are permitted. Inhaled/nebulized, intra-articular, intrabursal, or topical (skin, eyes, or ears) corticosteroids are permitted.
- •Receipt of blood/plasma products or immunoglobulin within 60 days before study intervention administration or planned receipt of these medications prior to the final blood draw.
- •Note: Monoclonal antibodies with targeted mechanisms of action used in the management of chronic illnesses (eg, migraine headaches, osteoporosis) are permitted, provided they do not meet exclusion criterion
- •Previous vaccination with any licensed or investigational RSV vaccine or planned receipt during study participation.
- •Participation in other studies involving an investigational product within 28 days prior to consent and/or through and including the 6-month follow-up visit.
- •Investigator site staff directly involved in the conduct of the study and their family members, site staff otherwise supervised by the investigator, and sponsor and sponsor delegate employees directly involved in the conduct of the study and their family members.
- •Substudy B Inclusion Criteria
- •Capable of giving signed informed consent as described per protocol.
- •Participants ≥18 years of age at study enrollment.
- •Life expectancy ≥12 months (365 days) in the opinion of the investigator at enrollment.
- •Participants who are willing and able to comply with all scheduled visits, vaccination plan, lifestyle considerations, and other study procedures.
- •Participants who are immunocompromised by virtue of the following:
- •Having known advanced NSCLC with at least 1 of the following:
- •Has received initial or maintenance chemotherapy at least 2 weeks (14 days) before enrollment (or is treatment-naïve), and is not expected to receive chemotherapy within at least 2 weeks (14 days) after dose administration of initial vaccination or second vaccination; and/or
- •Is receiving checkpoint inhibitor treatment (PD-1/PD-L1 inhibitor, CTLA-4 inhibitor) and has undergone at least 1 treatment cycle prior to enrollment; or
- •Is receiving targeted drug therapy (EGFR, ALK, ROS1, BRAF, RET, MET, NTRK inhibitors) and has undergone at least 1 treatment cycle prior to enrollment.
- •OR - Is currently undergoing maintenance hemodialysis treatment secondary to end-stage renal disease . OR - Is on active immunomodulator therapy (eg, TNFα inhibitor, tofacitinib, or MTX) for an autoimmune inflammatory disorder (eg, inflammatory arthritis, such as rheumatoid arthritis, psoriatic arthritis, and juvenile idiopathic arthritis, or inflammatory bowel disease, such as ulcerative colitis or Crohn's disease) at a stable*dose.
- •*Stable dose is defined as receiving the same dose for at least 3 months (84 days) with no changes in the 28 days prior to enrollment. See protocol for details on stable dose for MTX.
- •OR - Is receiving an SOT (kidney, liver, lung, or heart) at least 3 months (84 days) prior to enrollment (Visit 201) and with no acute rejection episodes within 2 months (60 days) prior to enrollment (Visit 201).
- •Substudy B Exclusion Criteria:
- •1.Bleeding diathesis or condition associated with prolonged bleeding that would, in the opinion of the investigator, contraindicate intramuscular injection.
- •2.History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (eg, anaphylaxis) to any component of the study intervention(s) or any related vaccine.
- •3.Participants with a history of transplant rejection, or PTLD, or participants who have had treatment for these conditions within 3 months (84 days) prior to study enrollment.
- •4.Participants who do not have adequate deltoid muscle mass to allow intramuscular vaccination, in the opinion of the investigator.
- •5.Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study.
- •Note: Specific criteria for participants with known stable infection with HIV can be found in protocol.
- •6.Receipt of investigational or approved monoclonal antibodies against RSV within 6 months before study intervention administration.
- •7.Receipt of blood/plasma products or immunoglobulin (IVIG, SCIG) within 60 days before study intervention administration or planned receipt of these medications prior to the final blood draw.
- •Note: Please see the inclusion criteria in the protocol regarding criteria for targeted immunoglobulin therapies for underlying medical conditions.
- •Note: Monoclonal antibodies with targeted mechanisms of action used in the management of chronic illnesses (eg, migraine headaches, osteoporosis) are permitted.
- •8.Previous vaccination with any licensed or investigational RSV vaccine or planned receipt during study participation.
- •9.Participation in other studies involving an investigational product within 28 days prior to consent and/or through and including the 6-month follow-up visit.
- •10.Investigator site staff directly involved in the conduct of the study and their family members, site staff otherwise supervised by the investigator, and sponsor and sponsor delegate employees directly involved in the conduct of the study and their family members.
研究组 & 干预措施
Substudy A - RSVpreF
Participants will receive a single 120-µg dose of RSVpreF at Visit 1
干预措施: RSVpreF (Biological)
Substudy A - Placebo
Participants will receive placebo at Visit 1
干预措施: Placebo (Other)
Substudy B - RSVpreF
Participants will receive 120-µg doses of RSVpreF at Visit 1 and Visit 2 (open label, single arm only)
干预措施: RSVpreF (Biological)
结局指标
主要结局
SSA: Percentage of Participants With Local Reactions Within 7 Days After Vaccination
时间窗: Within 7 Days after Vaccination (Vaccination on Day 1)
Local reactions included pain at injection site, redness and swelling, recorded by participants in an electronic diary (e-diary). Pain at injection site was graded as mild: did not interfere with activity; moderate: interfered with activity and severe: prevented daily activity. Redness and swelling were measured and recorded in measuring device units, where 1 measuring device unit =0.5 centimeter (cm). Redness and swelling were graded as mild: \>2.5 cm to 5.0 cm; moderate: \>5.0 cm to 10.0 cm; severe: \>10 cm.
SSA: Percentage of Participants With Systemic Events Within 7 Days After Vaccination
时间窗: Within 7 Days after Vaccination (Vaccination on Day 1)
Systemic events included fever, fatigue, headache, vomiting, nausea, diarrhea, muscle pain and joint pain. These were recorded by participants in an e-diary. Fever defined as oral temperature \>=38.0 degrees Celsius (deg C) and categorized as mild: \>=38.0 to 38.4 deg C, moderate: \>38.4 to 38.9 deg C and severe: \>38.9 to 40.0 deg C. Vomiting categorized as mild: 1-2 times in 24 hours (h); moderate: \>2 times in 24h; severe: required intravenous (IV) hydration. Diarrhea categorized as mild: 2-3 loose stools in 24h; moderate: 4-5 loose stools in 24h; severe: 6 or more loose stools in 24h. Headache, fatigue, nausea, muscle pain and joint pain were categorized as mild: didn't interfere with activity; moderate: some interference with activity; severe: prevented daily routine activity.
SSA: Percentage of Participants With Adverse Events (AEs) From Vaccination Through 1 Month After Vaccination
时间窗: Within 1 Month after Vaccination (Vaccination on Day 1)
An AE was defined as any untoward medical occurrence in a participant temporally associated with the use of study intervention, whether or not considered related to the study intervention. Only AEs collected by non-systematic assessment (i.e. excluding local reactions and systemic events) were included. AEs included both serious and all non-serious adverse events.
SSA: Percentage of Participants With Newly Diagnosed Chronic Medical Conditions (NDCMCs) From Vaccination Throughout the Study
时间窗: Within 6 Months after Vaccination (Vaccination on Day 1)
A NDCMC was defined as a disease or medical condition that was not identified prior to study start and was expected to be persistent or otherwise long-lasting in its effects. Newly diagnosed chronic medical condition did not include illnesses considered to be temporary conditions.
SSA: Percentage of Participants With Serious Adverse Events (SAEs) Throughout the Study
时间窗: Within 6 Months after Vaccination (Vaccination on Day 1)
An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention. An SAE was defined as any untoward medical occurrence that, at any dose, met one or more of the following criteria - resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect and was a suspected transmission via a Pfizer product of an infectious agent, pathogenic or non-pathogenic and other important medical event were included in this outcome measure.
SSA: Geometric Mean Ratio (GMR) Estimated by Ratio of the Geometric Mean Titers (GMTs) at 1 Month After Vaccination in Study C3671023 Participants Compared to Study C3671013 Adults >= 60 Years
时间窗: At 1 Month after Vaccination (Vaccination on Day 1)
In this outcome measure, GMTs for RSV A and RSV B neutralizing titers (NTs) are reported. In statistical section, GMT ratio estimated by the ratio of the GMTs for RSV A and RSV B serum NTs at 1 month after vaccination with RSVpreF in current study C3671023 participants to that in study C3671013 adults \>=60 years of age, is reported. GMTs and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on Student t distribution).
SSA: Percentage of Participants With Seroresponse Rate and Difference in Seroresponse Rates of RSV A and RSV B Serum NTs at 1 Month After Vaccination for Participants in Study C3671023 and C3671013 Adults >= 60 Years
时间窗: At 1 Month after Vaccination (Vaccination on Day 1)
Seroresponse was defined as achieving a \>=4-fold rise from baseline (before vaccination), if the baseline measurement was above the lower limit of quantitation (LLOQ). If the baseline measurement was below the LLOQ, a postvaccination assay result \>=4\* LLOQ was considered a seroresponse.
SSB: Percentage of Participants With Local Reactions Within 7 Days After Vaccination 1
时间窗: Within 7 Days after Vaccination 1 (Vaccination 1 on Day 1)
Local reactions included pain at injection site, redness and swelling, recorded by participants in an e-diary. Pain at injection site was graded as mild: did not interfere with activity; moderate: interfered with activity and severe: prevented daily activity. Redness and swelling were measured and recorded in measuring device units, where 1 measuring device unit=0.5 cm. Redness and swelling were graded as mild: \> 2.0 cm to 5.0 cm; moderate: \> 5.0 cm to 10.0 cm and severe: \> 10 cm.
SSB: Percentage of Participants With Local Reactions Within 7 Days After Vaccination 2
时间窗: Within 7 Days after Vaccination 2 (Vaccination 2: 1-month post-vaccination 1 on Day 1)
Local reactions included pain at injection site, redness and swelling, recorded by participants in an e-diary. Pain at injection site was graded as mild: did not interfere with activity; moderate: interfered with activity and severe: prevented daily activity. Redness and swelling were measured and recorded in measuring device units, where 1 measuring device unit = 0.5 cm. Redness and swelling were graded as mild: \>2.0 cm to 5.0 cm; moderate: \>5.0 cm to 10.0 cm and severe: \>10 cm.
SSB: Percentage of Participants With Systemic Events Within 7 Days After Vaccination 1
时间窗: Within 7 Days after Vaccination 1 (Vaccination 1 on Day 1)
Systemic events included fever, fatigue, headache, vomiting, nausea, diarrhea, muscle pain and joint pain. These were recorded by participants in an e-diary. Fever defined as oral temperature \>=38.0 degrees Celsius (deg C) and categorized as mild: \>=38.0 to 38.4 deg C, moderate: \>38.4 to 38.9 deg C and severe: \>38.9 to 40.0 deg C. Vomiting categorized as mild: 1-2 times in 24 hours (h); moderate: \>2 times in 24h; severe: required intravenous (IV) hydration. Diarrhea categorized as mild: 2-3 loose stools in 24h; moderate: 4-5 loose stools in 24h; severe: 6 or more loose stools in 24h. Headache, fatigue, nausea, muscle pain and joint pain were categorized as mild: didn't interfere with activity; moderate: some interference with activity; severe: prevented daily routine activity.
SSB: Percentage of Participants With Systemic Events Within 7 Days After Vaccination 2
时间窗: Within 7 Days after Vaccination 2 (Vaccination 2: 1-month post-vaccination 1 on Day 1)
Systemic events included fever, fatigue, headache, vomiting, nausea, diarrhea, muscle pain and joint pain. These were recorded by participants in an e-diary. Fever defined as oral temperature \>=38.0 degrees Celsius (deg C) and categorized as mild: \>=38.0 to 38.4 deg C, moderate: \>38.4 to 38.9 deg C and severe: \>38.9 to 40.0 deg C. Vomiting categorized as mild: 1-2 times in 24 hours (h); moderate: \>2 times in 24h; severe: required intravenous (IV) hydration. Diarrhea categorized as mild: 2-3 loose stools in 24h; moderate: 4-5 loose stools in 24h; severe: 6 or more loose stools in 24h. Headache, fatigue, nausea, muscle pain and joint pain were categorized as mild: didn't interfere with activity; moderate: some interference with activity; severe: prevented daily routine activity.
SSB: Percentage of Participants With AEs From Vaccination 1 Through 1 Month After Vaccination 2
时间窗: From Vaccination 1 (on Day 1) through 1 month after Vaccination 2 (1 month after Vaccination 1) [approximately up to maximum of 2 months]
An AE was defined as any untoward medical occurrence in a participant temporally associated with the use of study intervention, whether or not considered related to the study intervention. Only AEs collected by non-systematic assessment (i.e. excluding local reactions and systemic events) were included. AEs included both serious and all non-serious adverse events.
SSB: Percentage of Participants With NDCMCs From Vaccination Throughout the Study
时间窗: From Vaccination 1 (on Day 1) through 6 months after Vaccination 2 (1 month after Vaccination 1) [approximately up to maximum of 7 months]
A NDCMC was defined as a disease or medical condition that was not identified prior to study start and was expected to be persistent or otherwise long-lasting in its effects. Newly diagnosed chronic medical condition did not include illnesses considered to be temporary conditions.
SSB: Percentage of Participants With SAEs Throughout the Study
时间窗: From Vaccination 1 (on Day 1) through 6 months after Vaccination 2 (1 month after Vaccination 1) [approximately up to maximum of 7 months]
An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention. An SAE was defined as any untoward medical occurrence that, at any dose, met one or more of the following criteria - resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect and was a suspected transmission via a Pfizer product of an infectious agent, pathogenic or non-pathogenic and other important medical event were included in this outcome measure.
SSB: GMT of NT for RSV A and RSV B Before Vaccination 1
时间窗: Before Vaccination 1 (on Day 1)
GMT of RSV A and RSV B before vaccination were reported in this outcome measure. Assay results below the lower limit of quantification (LLOQ) were set to 0.5\*LLOQ. GMTs and 2-sided 95% CIs were calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on the Student t distribution).
SSB: GMT of NT for RSV A and RSV B 1 Month After Vaccination 1
时间窗: 1 Month After Vaccination 1 (on Day 1)
GMT of RSV A and RSV B before vaccination were reported in this outcome measure. Assay results below the lower limit of quantification (LLOQ) were set to 0.5\*LLOQ. GMTs and 2-sided 95% CIs were calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on the Student t distribution).
SSB: GMT of NT for RSV A and RSV B 1 Month After Vaccination 2
时间窗: 1 Month After Vaccination 2 (1-month post Vaccination 1)
GMT of RSV A and RSV B before vaccination were reported in this outcome measure. Assay results below the lower limit of quantification (LLOQ) were set to 0.5\*LLOQ. GMTs and 2-sided 95% CIs were calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on the Student t distribution).
次要结局
- SSA: GMFR of NTs for RSV A and RSV B From Before Vaccination to 1 Month After Vaccination(SSA: Before Vaccination (on Day 1) and 1 Month After Vaccination)
- SSB: Geometric Mean Fold Rise (GMFR) of NTs for RSV A and RSV B From Vaccination 1 to 1 Month Post-Vaccination 1(At 1 Month After Vaccination 1 (on Day 1) to 1 Month Post-Vaccination 1)
- SSB: GMFR of NTs for RSV A and RSV B From Vaccination 1 to 1 Month Post-Vaccination 2(At 1 Month After Vaccination 1 (on Day 1) to 1 Month Post-Vaccination 2)
- SSA: GMT of NTs for RSV A and RSV B Before Vaccination and 1 Month After Vaccination(SSA: Before Vaccination (on Day 1) and 1 Month After Vaccination)