Randomised Controlled Trials to Assess Approved SARS-CoV-2 Vaccines in Immunocompromised Patients: A Master Protocol for the Set-up of a Swiss Cohorts Based Trial Platform
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 610
- 试验地点
- 8
- 主要终点
- SARS-CoV-2-specific titers
研究概览
简要总结
This study is to set up a flexible trial platform using two existing national cohorts of immunocompromised patients (i.e. Swiss HIV Cohort Study [SHCS] and Swiss Transplant Cohort Study [STCS]) to assess the comparative effectiveness and safety of approved SARS-CoV-2 vaccines in immunocompromised patients.
This platform will be tested in the frame of an exploratory pilot trial and a framework will be set up to conduct a larger, flexible, randomized controlled trial (RCT) to test approved SARS-CoV-2 vaccines to prevent SARS-CoV-2 infections.
The first sub-protocol for a pilot trial is to investigate the operability of a platform trial that is nested into two existing cohort studies and compare immune response, safety and clinical efficacy of the first two mRNA vaccines (Comirnaty® by Pfizer / BioNTech and COVID-19 mRNA Vaccine Moderna®, by Moderna) in immune compromised patients in the Swiss HIV and Swiss Transplant Cohort studies.
The second sub-protocol (observational study) is to collect a blood sample before the third vaccination and 8 weeks after vaccination to analyze an additional benefit of a third SARS-CoV-2 vaccine in these immunocompromised patients.
In the third sub-protocol (substudy-3; observational) we will recruit patients who have received m-RNA-1273.214 by Moderna in the frame of clinical routine. We will start a second arm of our observational study as soon as another bivalent mRNA vaccine (from Pfizer-BioNTech) has been approved by Swissmedic. We aim to compare the immunologic response and safety of the bivalent mRNA-1273.214 vaccine from Moderna among immunocompromised persons (persons living with HIV or kidney or lung transplant recipients) to the immunologic response of immunocompromised persons who received the bivalent mRNA vaccine from Pfizer-BioNTech.
详细描述
The aim of this study is to set up a flexible trial platform using two existing national cohorts of immunocompromised patients (i.e. Swiss HIV Cohort Study [SHCS] and Swiss Transplant Cohort Study [STCS]) to assess the comparative effectiveness and safety of approved SARS-CoV-2 vaccines in immunocompromised patients. Nesting this trial into cohorts with highly standardized data collection allows for a rapid, efficient and cost-saving trial conduct.
This platform will be tested in the frame of a pilot trial and a framework will be set up to conduct a larger, flexible, randomized controlled trial (RCT) to test approved SARS-CoV-2 vaccines to prevent SARS-CoV-2 infections.
The pilot study will primarily assess the functionality of the trial platform and early immunogenicity, efficacy and safety data. At a later stage, the platform might also be used to enlarge the pilot trial or to develop sub-protocols to deal with patients with no or insufficient immune response to Sars-CoV-2 vaccines.
Since January 12, 2021 two mRNA vaccines against Sars-CoV-2 by Pfizer / BioNTech (Comirnaty®) and COVID-19 mRNA Vaccine Moderna® by Moderna have been licensed in Switzerland and roll-out of vaccines has started
The first sub-protocol for a pilot trial is to investigate the operability of a platform trial that is nested into two existing cohort studies and compare immune response, safety and clinical efficacy of the first two mRNA vaccines (Comirnaty® by Pfizer / BioNTech and COVID-19 mRNA Vaccine Moderna®, by Moderna) in immune compromised patients in the Swiss HIV and Swiss Transplant Cohort studies.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- None
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
- •All patients registered with informed consent from participating cohorts aged ≥18 years
- •Additional consent for participation in the specific sub-protocol trial
- •Inclusion criteria for pilot trial:
- •All patients with either a chronic HIV infection or recipients of solid organs registered with informed consent from the SHCS and STCS cohorts aged ≥18 years
- •Patients with solid organ transplantation of lungs or kidneys at least one month post-transplantation with a prednisone dose of 20mg or less.
- •Covid-19 vaccination recommended by treating physician
- •Inclusion criteria for
- •sub protocol (observational study):
- •Third covid-19 vaccination recommended by treating physician and administered in the frame of clinical routine
- •Inclusion criteria for
- •Patients receiving a new bivalent (Wuhan/Omicron BA.1) mRNA SARS-CoV-2 vaccine in the frame of clinical routine, according to the treating physician
排除标准
- •Acute symptomatic SARS-CoV-2 infection, influenza or other acute respiratory tract infection
- •Known allergy or contra-indications for vaccines or any vaccine components
- •Any emergency condition requiring immediate hospitalization for any condition
- •Patients with previous PCR documented SARS-CoV-2 infection and, or documented antibodies less than 3 months prior to screening visit (day 0)
- •Exclusion criteria for pilot trial:
- •Pregnancy
- •Acute symptomatic SARS-CoV-2 infection, influenza or other acute respiratory tract infection
- •Known allergy or contra-indications for vaccines or any vaccine components
- •Any emergency condition requiring immediate hospitalization for any condition
- •Patients with previous PCR documented SARS-CoV-2 infection and, or documented antibodies less than 3 months prior to randomisation
- •Patients with solid organ transplantation (lung or kidney) with the following conditions:
- •Solid organ transplant recipients less than one month post-transplantation
- •Solid organ transplant recipients with the use of T-cell/B-cell depleting agents in the last 3 months (i. e induction treatment in standard risk or high-risk immunological situation or rejection treatment).
- •Solid organ transplant recipients with the need of pulse corticosteroids (>100mg prednisone or equivalent) in the last 1 month or who have received ATG or rituximab in the last 6 months
- •Solid organ transplant recipients with the need of any kind of chemotherapy treatment
结局指标
主要结局
SARS-CoV-2-specific titers
时间窗: three months after vaccination
SARS-CoV-2-specific titers (using an in-house assay developed by the Institute of Medical Virology, University of Zurich which can detect multiple viral epitopes)
immunological outcome: change in pan-Ig antibody response (pan-Ig anti-S1-RBD)
时间窗: at baseline (day of vaccination) and three months after vaccination
A commercial immunoassay Elecsys® Anti-SARS-CoV-2 S for the in vitro quantitative determination of antibodies to the SARS-CoV-2 spike (S) protein receptor binding domain (RBD) in human serum and plasma is used. This assay detects pan-Ig antibody response (pan-Ig anti-S1-RBD) and allows for a quantitative assessment of the serological response of the participants.
immunological outcome: change in anti-Nucleocapsid (N) response
时间窗: at baseline (day of vaccination) and three months after vaccination
Qualitative measurement of anti-Nucleocapsid (N) responses with Elecsys® Anti-SARS-CoV-2 N assay
SARS-CoV-2-specific antibodies
时间窗: three months after vaccination
SARS-CoV-2-specific antibodies (using a pan-IgG antibody assay against the receptor binding domain (RBD) against the nP and spike 1 subunits)
The proportion of patients with a positive antibody response to SARS-CoV-2 spike (S1) protein receptor binding domain in human serum or plasma assessed in the observational second sub- protocol
时间窗: 8 weeks (¨+/- 2 weeks) after 3. vaccination
The proportion of patients with a positive antibody response to SARS-CoV-2 spike (S1) protein receptor binding domain in human serum or plasma assessed or plasma assessed in the observational second sub- protocol by the commercial immunoassay Elecsys Anti-SARS-CoV-2 S (Elecsys S) from Roche Diagnostics. An antibody response will be considered as positive using the threshold ≥ 100 units/ml, predicting a protective immune response.
Time of patient recruitment from activation of first study site until 40 patients are randomised
时间窗: one time assessment after approx. 3 months (from activation of first study site until 40 patients are randomised)
Time of patient recruitment from activation of first study site until 40 patients are randomised
Proportion of missing data for all baseline variables from routinely collected cohort data
时间窗: one time assessment at baseline
Proportion of missing data for all baseline variables from routinely collected cohort data
Number of participants with newly polymerase chain reaction (PCR)-confirmed asymptomatic COVID-19 infection
时间窗: at any time point in within 48 weeks following randomisation (day of vaccination)
Number of participants with newly PCR-confirmed asymptomatic COVID-19 infection (identified by the presence of anti-SARS-CoV-2 nucleocapsid antibodies or Sars-Cov-2 PCR or rapid antigen test) and no related symptoms \[(i.e. fever or chills, cough, shortness of breath or difficulty breathing, fatigue, muscle or body aches, headache, new loss of taste or smell, sore throat, congestion or runny nose nausea or vomiting, and diarrhea\])
Clinical Outcome: COVID-19 burden of diseases (BOD)
时间窗: within 48 weeks following randomisation (day of vaccination)
COVID-19 burden of diseases (BOD), a composite, will be scored as by using 0 for no COVID-19, 1 for non-severe COVID-19, and 2 for severe COVID-19.
Duration of RCT set up (specific endpoint related to trial conduct feasibility)
时间窗: one time assessment at baseline (from deciding which interventions will be tested until the first patient is randomised)
Duration of RCT set up (i.e. time from deciding which interventions will be tested until the first patient is randomised).
Patient consent rate
时间窗: approx. 3 months
Patient consent rate (i.e. proportion of patients giving informed consent out of approached eligible patients)
immunological outcome: change in SARS-CoV-2-binding antibodies
时间窗: at baseline (day of vaccination) and three months after vaccination
SARS-CoV-2-binding antibody responses of the participants are assessed by analyzing the IgM, IgA and IgG responses to a wider range of SARS-CoV-2 proteins (S1, S2, RBD and N) using an in-house method (ABCORA). The ABCORA test allows a parallel assessment of IgG, IgM and IgA reactivity.
Number of participants with newly PCR-confirmed symptomatic COVID-19 infection
时间窗: at any time point in within 48 weeks following randomisation (day of vaccination)
Number of participants with newly PCR-confirmed symptomatic COVID-19 infection with at least one of the following symptoms (i.e. fever or chills, cough, shortness of breath or difficulty breathing, fatigue, muscle or body aches, headache, new loss of taste or smell, sore throat, congestion or runny nose nausea or vomiting, and diarrhea
Number of participants with severe COVID-19 infection
时间窗: at any time point in within 48 weeks following randomisation (day of vaccination)
Number of participants with severe COVID-19 infection with respiratory failure, evidence of shock (as diagnosed by a treating physician), clinically significant acute renal, hepatic, or neurologic dysfunction; admission to an intensive care unit; or death
Time of patient recruitment from activation of first study site until 380 patients are randomised
时间窗: one time assessment after approx. 3 months (from activation of first study site until 380 patients are randomised)
Time of patient recruitment from activation of first study site until 380 patients are randomised
Proportion of missing data for all clinical outcomes
时间窗: one time assessment after approx. 3 months
Proportion of missing data for all clinical outcomes from routinely collected cohort data and outcome data that is collected in the trial platform
次要结局
- The proportion of patients with neutralizing neutralization activity against the vaccine strain Wuhan-Hu-1 in the observational second sub- protocol(8 weeks (¨+/- 2 weeks) after 3. vaccination)
- Mean immune response of IgM, IgA and IgG to the subunit S1 using ABCORA in the observational second sub- protocol(8 weeks (¨+/- 2 weeks) after 3. vaccination)
- Number of newly PCR-confirmed asymptomatic SARS-CoV-2 infection in the observational second sub- protocol(8 weeks (¨+/- 2 weeks) after 3. vaccination)
- The proportion of patients with a positive antibody response using SARS-CoV-2 spike (S1) Elecsys S by Roche in the observational second sub- protocol, using a threshold of ≥0.8 units/ml as defined by the manufacturer(8 weeks (¨+/- 2 weeks) after 3. vaccination)
- The proportion of patients with a positive antibody response using antibody response using the Antibody CORonavirus Assay (ABCORA) 2 in the observational second sub- protocol(8 weeks (¨+/- 2 weeks) after 3. vaccination)
- Immune response (pan-Ig antibodies against the receptor binding domain (RBD) in the S1 subunit of the spike protein (pan-Ig anti-S1-RBD) of SARS-CoV-2 in the observational second sub- protocol(8 weeks (¨+/- 2 weeks) after 3. vaccination)