A Phase IV Open-Label, Non-Randomized, Multi-Cohort, Multicenter Study in Previously Unvaccinated Immunocompromised Adults to Determine the Immunogenicity and Safety of AZD1222 Vaccine for the Prevention of COVID-19
试验速览
- 阶段
- 4 期
- 状态
- 终止
- 发起方
- AstraZeneca
- 入组人数
- 34
- 试验地点
- 1
- 主要终点
- Geometric Mean Titers (GMT) for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Neutralizing Antibodies (nAb) Post 2-Dose Primary Vaccination of AZD1222 as Measured by Pseudo-neutralization Assay
研究概览
简要总结
The aim of this study is to assess the immunogenicity and safety of AZD1222 for prevention of COVID-19 in immunocompromised adults.
详细描述
The purpose of this study is to demonstrate the immunogenicity and safety of AZD1222, AstraZeneca's approved ChAdOx1 vector vaccine against SARS-CoV-2, in SARS-CoV-2 seronegative immunocompromised individuals who are unvaccinated.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 130 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Adult, ≥ 18 years at the time of signing the informed consent.
- •Cohort specific inclusion criteria:
- •Solid organ transplant
- •Participants with heart, lung, kidney, or liver transplant, and are stable on immunosuppressants (defined as no change in dose in the previous 4 weeks).
- •Hematopoietic stem cell transplant
- •Participants with autologous (up to 6 months after transplantation) or allogeneic stem cell transplant who are immunosuppressed, with no evidence of active graft-versushost disease, at least one month after the procedure.
- •Cancer patients on chemotherapy
- •Participants with solid tumors (except breast cancer), histologically diagnosed, who were undergoing intravenous cytotoxic chemotherapy within the last 6 months, who received at least 1 cycle prior to cytotoxic chemotherapy, and have a life expectancy of longer than 3 months.
- •Chronic inflammatory conditions
- •Participants with chronic inflammatory conditions, including those on immunosuppressant medications, can be recruited. The following conditions are specifically excluded: multiple sclerosis and peripheral demyelinating disease.
- •Primary immune deficiency
- •Examples include combined granulomatous disorder, SCID, common variable immunodeficiency.
- •Immunocompetent:
- •No confirmed or suspected immunosuppressive or immunodeficient state.
- •No use of immunosuppressant medication within the past 1 month (≥ 20 mg per day of prednisone or its equivalent, given daily or on alternate days for ≥ 15 days within 30 days prior to administration of AZD1222). The following exceptions are permitted: topical/inhaled steroids or short-term oral steroids (course lasting ≤ 14 days).
- •No receipt of immunoglobulins and/or any blood products within 3 months prior to administration of AZD1222 or expected receipt during the period of study follow up.
- •No severe and/or uncontrolled cardiovascular disease, respiratory disease, gastrointestinal disease, liver disease, renal disease, endocrine disorder, and neurological illness, as judged by the Investigator.
排除标准
- •History of allergic disease or reactions likely to be exacerbated by any component of AZD
- •Active infection with SARS-CoV-2 as confirmed locally by nucleic acid amplification test (e.g. RT-PCR).
- •Known current or past laboratory-confirmed SARS-CoV-2 infection.
- •Significant infection or other acute illness, including fever (temperature > 37.8°C) on the day prior to or day of first dosing.
- •Thrombocytopenia with platelet count ≤ 75,000 x 109/microliter based on complete blood count test at screening visit.
- •HIV-positive participants based on a positive ELISA test performed at screening visit.
- •History of cerebral venous sinus thrombosis (CVST).
- •Receipt of any vaccine (licensed or investigational) within 30 days prior to and after administration of AZD1222.
研究组 & 干预措施
Cohort 1 - immunocompromised participants with solid organ transplant
Previously unvaccinated immunocompromised participants with solid organ transplant will receive a primary vaccination series with 3 IM doses of AZD1222 separated by 4 weeks and will be followed to the end of the study. The first dose will be administered on Day 1, the second dose will be administered 28 days after dose 1, and the third dose will be administered 28 days after dose 2.
干预措施: AZD1222 (Biological)
Cohort 2 - immunocompromised participants with hematopoietic stem cell transplant
Previously unvaccinated immunocompromised participants with hematopoietic stem cell transplant will receive a primary vaccination series with 3 IM doses of AZD1222 separated by 4 weeks and will be followed to the end of the study. The first dose will be administered on Day 1, the second dose will be administered 28 days after dose 1, and the third dose will be administered 28 days after dose 2.
干预措施: AZD1222 (Biological)
Cohort 5 - immunocompromised participants with primary immunodeficiency
Previously unvaccinated immunocompromised participants with primary immunodeficiency will receive a primary vaccination series with 3 IM doses of AZD1222 separated by 4 weeks and will be followed to the end of the study. The first dose will be administered on Day 1, the second dose will be administered 28 days after dose 1, and the third dose will be administered 28 days after dose 2.
干预措施: AZD1222 (Biological)
Cohort 3 - immunocompromised participants with solid organ cancer receiving cytotoxic chemotherapy
Previously unvaccinated immunocompromised participants with solid organ cancer receiving cytotoxic chemotherapy will receive a primary vaccination series with 3 IM doses of AZD1222 separated by 4 weeks and will be followed to the end of the study. The first dose will be administered on Day 1, the second dose will be administered 28 days after dose 1, and the third dose will be administered 28 days after dose 2.
干预措施: AZD1222 (Biological)
Cohort 4 - immunocompromised participants with chronic inflammatory disorders
Previously unvaccinated immunocompromised participants with chronic inflammatory disorders will receive a primary vaccination series with 3 IM doses of AZD1222 separated by 4 weeks and will be followed to the end of the study. The first dose will be administered on Day 1, the second dose will be administered 28 days after dose 1, and the third dose will be administered 28 days after dose 2.
干预措施: AZD1222 (Biological)
Cohort 6 - immunocompetent participants
Previously unvaccinated immunocompetent participants will receive a primary vaccination series with 2 IM doses of AZD1222 separated by 4 weeks, followed by a booster dose of AZD1222 administered 6 months after the first dose. The first dose will be administered on Day 1, the second dose will be administered 28 days after dose 1. Participants will receive a third dose booster 6 months after dose 1 and will continue to be followed to the end of the study.
干预措施: AZD1222 (Biological)
结局指标
主要结局
Geometric Mean Titers (GMT) for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Neutralizing Antibodies (nAb) Post 2-Dose Primary Vaccination of AZD1222 as Measured by Pseudo-neutralization Assay
时间窗: Days 29 and 57
The GMT was calculated as the antilogarithm of Σ (base 2 log transformed titer/n), that is (i.e.), as the antilogarithm transformation of the mean of the log-transformed titer, where n is the number of participants with titer information.
Percentage of Participants With Seroresponse to SARS-CoV-2 nAb Post 2-Dose Primary Vaccination of AZD1222 as Measured by Pseudo-neutralization Assay
时间窗: Days 29 and 57
The fold rise was calculated as the ratio of the post-vaccination titer level to the pre-vaccination titer level. The percentage of participants with a post-intervention seroresponse (\>=4-fold rise in titers from baseline value to 28 days post doses 1 and 2) to SARS-CoV-2 nAb of AZD1222 as measured by pseudo-neutralization assay is reported. The 2-sided 95% CI was calculated using Clopper-Pearson methodology.
GMT for SARS-CoV-2 Anti-Spike Binding Antibodies Post 2-Dose Primary Vaccination of AZD1222 as Measured by Meso Scale Discovery (MSD) Serology Assay
时间窗: Days 29 and 57
The GMT was calculated as the antilogarithm of Σ (base 2 log transformed titer/n), i.e, as the antilogarithm transformation of the mean of the log-transformed titer, where n is the number of participants with titer information.
Percentage of Participants With Seroresponse to Anti-Spike Binding Antibodies of a 2-Dose Primary Vaccination of AZD1222 as Measured by MSD Serology Assay
时间窗: Days 29 and 57
The fold rise was calculated as the ratio of the post-vaccination titer level to the pre-vaccination titer level. The percentage of participants with a post-intervention seroresponse (\>=4-fold rise in titers from baseline value to 28 days post doses 1 and 2) to anti-spike binding antibodies of AZD1222 as measured by MSD serology assay is reported. The 2-sided 95% CI was calculated using Clopper-Pearson methodology.
次要结局
- GMT for SARS-CoV-2 nAb Post Second Dose of AZD1222 as Measured by Pseudo-neutralization Assay(Day 57)
- Percentage of Participants With Seroresponse to SARS-CoV-2 nAb Post Second Dose of AZD1222 as Measured by Pseudo-neutralization Assay(Day 57)
- GMT for SARS-CoV-2 Anti-Spike Binding Antibodies Post Second Dose of AZD1222 as Measured by MSD Serology Assay(Day 57)
- Percentage of Participants With Seroresponse to SARS-CoV-2 Anti-Spike Binding Antibodies Post Second Dose of AZD1222 as Measured by MSD Serology Assay(Day 57)
- GMT for SARS-CoV-2 nAb Post Third Dose of AZD1222 as Measured by Pseudo-neutralization Assay(Day 85 for immunocompromised cohort and Day 211 for immunocompetent cohort)
- Percentage of Participants With Seroresponse to SARS-CoV-2 nAb Post Third Dose of AZD1222 as Measured by Pseudo-neutralization Assay(Day 85 for immunocompromised cohort and Day 211 for immunocompetent cohort)
- GMT for SARS-CoV-2 Anti-Spike Binding Antibodies Post Third Dose of AZD1222 as Measured by MSD Serology Assay(Day 85 for immunocompromised cohort and Day 211 for immunocompetent cohort)
- Percentage of Participants With Seroresponse to Anti-Spike Binding Antibodies Post Third Dose of AZD1222 as Measured by MSD Serology Assay(Day 85 for immunocompromised cohort and Day 211 for immunocompetent cohort)