Multi-Center, Randomized, Efficacy Study of COVID-19 mRNA Vaccine in Regions With SARS-CoV-2 Variants of Concern
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 14,237
- 试验地点
- 84
- 主要终点
- Part B: Number of Participants With Solicited Adverse Events in the Safety Subset
研究概览
简要总结
The study will evaluate the clinical efficacy of different dosing regimens of the Moderna COVID-19 mRNA vaccine (100 mcg) in preventing COVID-19 disease in people who are living with HIV or have comorbidities associated with elevated risk of severe COVID-19, with the different vaccine regimens assessed determined by whether the participant had evidence of prior SARS-CoV-2 infection at enrollment.
详细描述
The study is constructed to help inform which vaccine regimen, likely in combination with enhanced HIV care, could serve as a public health model for an effective and cost-efficient approach to preventing SARS-CoV-2 disease, prolonged viral shedding, and the emergence of VOCs within this population. Moreover, we will evaluate whether immune responses postvaccination can be correlated to these clinically important outcomes.
The study will enroll 15,600 adults from many clinics in Eastern and Southern Africa. All participants in the study will get the study vaccine. There are 4 primary groups in this study. The groups differ in the number of doses of the study vaccine administered. The groups are organized by whether or not people are living with HIV and whether or not people have evidence of prior SARS-CoV-2 infection in their blood.
Group 1 includes people living with HIV and Group 3 includes people who are not living with HIV. All people in groups 1 and 3 will have no evidence of prior SARS-CoV-2 infection in their blood. Participants in Group 1 or Group 3 will get three doses of the study vaccine.
Group 2 includes people living with HIV and Group 4 includes people who are not living with HIV. All people in groups 2 and 4 will have evidence of prior SARS-CoV-2 infection in their blood. Participants in Group 2 or Group 4 will get two doses of the study vaccine.
There are 8 scheduled clinic visits over 18 months. Study visits may include physical examinations, medical history, vaccine injections, HIV testing, blood collection, nasal swabs, and questionnaires.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •General and Demographic Criteria
- •Age ≥ 18 years if participant self-reports living with HIV or another comorbidity known to be associated with severe COVID-19, for example (CDC.gov for exhaustive list):
- •Hypertension
- •Type 2 diabetes mellitus
- •Overweight, obese, or severely obese (ie, body mass index [BMI] ≥ 25 kg/m2)
- •Heart conditions, such as heart failure, coronary artery disease, or cardiomyopathies
- •Chronic kidney disease
- •COPD (chronic obstructive pulmonary disease)
- •Non-HIV immunocompromised state (weakened immune system) or solid organ transplant
- •Pregnancy
- •Sickle cell disease
- •Willingness to be followed and remain in the catchment area for the planned duration of the study.
- •Ability and willingness to provide informed consent.
- •Willingness to discuss HIV infection status, undergo related testing/monitoring labs, and receive counseling and referrals to minimize HIV acquisition/improve HIV care as appropriate based on their infection status.
- •Assessment of Understanding (AoU): Participant demonstrates understanding of this study; completes a questionnaire prior to first vaccination with demonstration of understanding of all questionnaire items answered incorrectly.
- •Agrees not to enroll in another interventional study of an investigational research agent until after the study is completed and all the data has been obtained. Enrollment in studies of investigational research agents for the treatment of COVID-19 is allowed for participants who develop COVID-19 disease.
排除标准
- •Acutely ill 72 hours prior to or at screening. Participants meeting this criterion may be rescheduled within the relevant window periods. Participants with minor illnesses can be enrolled at the discretion of the investigator.
- •History of angioedema or anaphylaxis.
- •Vaccines and other injections
- •Prior receipt of a SARS-CoV-2 vaccine.
- •History of severe allergic reaction to any ingredient of this vaccine (lipids (SM-102, polyethylene glycol [PEG] 2000 dimyristoyl glycerol [DMG], cholesterol, and 1,2-distearoyl-sn-glycero-3-phosphocholine [DSPC]), tromethamine, tromethamine hydrochloride, acetic acid, sodium acetate trihydrate, and sucrose).
- •Live attenuated vaccines received within 30 days before first vaccination (eg, measles, mumps, and rubella [MMR]; oral polio vaccine [OPV]; varicella; yellow fever; live attenuated influenza vaccine, live attenuated zoster vaccine).
- •Any vaccines that are not live attenuated vaccines and were received within 14 days prior to first vaccination (eg, tetanus, human papilloma virus (HPV), pneumococcal, Hepatitis A or B).
- •Blood products, systemic immunoglobulins, or monoclonal antibodies (including against SARS-CoV-2) received within 90 days before first vaccination.
研究组 & 干预措施
Study Group 1
COVID-19 mRNA vaccine in 100 mcg dose to be administered as an IM injection into the deltoid muscle on Months 0, 1, and 6 among adults living with HIV who are SARS-CoV-2 negative at baseline.
干预措施: Vaccine 3 Dose (Biological)
Study Group 2
COVID-19 mRNA vaccine in 100 mcg dose to be administered as an IM injection into the deltoid muscle on Months 0 and 6 among adults living with HIV who are SARS-CoV-2 positive at baseline.
干预措施: Moderna mRNA-1273 (Biological)
Study Group 2
COVID-19 mRNA vaccine in 100 mcg dose to be administered as an IM injection into the deltoid muscle on Months 0 and 6 among adults living with HIV who are SARS-CoV-2 positive at baseline.
干预措施: Moderna mRNA-1273.222 (Biological)
Study Group 2
COVID-19 mRNA vaccine in 100 mcg dose to be administered as an IM injection into the deltoid muscle on Months 0 and 6 among adults living with HIV who are SARS-CoV-2 positive at baseline.
干预措施: Vaccine 2 Dose (Biological)
Study Group 3
COVID-19 mRNA vaccine in 100 mcg dose to be administered as an IM injection into the deltoid muscle on Months 0, 1, and 6 among HIV negative adults who are SARS-CoV-2 negative at baseline.
干预措施: Moderna mRNA-1273 (Biological)
Study Group 3
COVID-19 mRNA vaccine in 100 mcg dose to be administered as an IM injection into the deltoid muscle on Months 0, 1, and 6 among HIV negative adults who are SARS-CoV-2 negative at baseline.
干预措施: Moderna mRNA-1273.222 (Biological)
Study Group 3
COVID-19 mRNA vaccine in 100 mcg dose to be administered as an IM injection into the deltoid muscle on Months 0, 1, and 6 among HIV negative adults who are SARS-CoV-2 negative at baseline.
干预措施: Vaccine 3 Dose (Biological)
Study Group 4
COVID-19 mRNA vaccine in 100 mcg dose to be administered as an IM injection into the deltoid muscle on Months 0 and 6 among HIV negative adults who are SARS-CoV-2 positive at baseline.
干预措施: Moderna mRNA-1273 (Biological)
Study Group 4
COVID-19 mRNA vaccine in 100 mcg dose to be administered as an IM injection into the deltoid muscle on Months 0 and 6 among HIV negative adults who are SARS-CoV-2 positive at baseline.
干预措施: Moderna mRNA-1273.222 (Biological)
Monovalent
mRNA-1273 vaccine in 100 mcg dose to be administered as an IM injection into the deltoid muscle on Month 6.
干预措施: Moderna mRNA-1273 (Biological)
Bivalent
mRNA-1273.222 vaccine in 100 mcg dose to be administered as an IM injection into the deltoid muscle on Month 6.
干预措施: Moderna mRNA-1273.222 (Biological)
Study Group 1
COVID-19 mRNA vaccine in 100 mcg dose to be administered as an IM injection into the deltoid muscle on Months 0, 1, and 6 among adults living with HIV who are SARS-CoV-2 negative at baseline.
干预措施: Moderna mRNA-1273 (Biological)
Study Group 1
COVID-19 mRNA vaccine in 100 mcg dose to be administered as an IM injection into the deltoid muscle on Months 0, 1, and 6 among adults living with HIV who are SARS-CoV-2 negative at baseline.
干预措施: Moderna mRNA-1273.222 (Biological)
Study Group 4
COVID-19 mRNA vaccine in 100 mcg dose to be administered as an IM injection into the deltoid muscle on Months 0 and 6 among HIV negative adults who are SARS-CoV-2 positive at baseline.
干预措施: Vaccine 2 Dose (Biological)
结局指标
主要结局
Part B: Number of Participants With Solicited Adverse Events in the Safety Subset
时间窗: Up to 7 days following Month 6 vaccination
All solicited adverse events/reactogenicity symptoms are followed until resolution and graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, dated July 2017. Local reacto symptoms collected are: erythema/redness, induration/swelling, lymphadenopathy, and pain/tenderness. Systemic reacto symptoms collected are: arthralgia, chills, fever, headache, malaise/fatigue, myalgia, and nausea.
Part A: Number of Participants With a First Occurrence of CDC-defined COVID-19 Starting 1 Day After Month 0 Dose Until Month 6 Dose in FAS Cohort Between Analysis Group 1 (AG1) and Analysis Group 2-1 (AG2-1)
时间窗: 1 day after Month 1 dose until Month 6 dose
The CDC-based COVID-19 endpoint is defined as the first occurrence of symptomatic NAAT-confirmed COVID-19 based on the following criteria: 1. At least ONE of the following systemic or respiratory symptoms: Fever (≥ 38C), chills, cough, shortness of breath and/or difficulty breathing, fatigue, muscle and/or body aches \[not related to exercise\], headache, new loss of taste/smell, sore throat, congestion, runny nose, nausea, vomiting, or diarrhea, AND 2. At least ONE (post-baseline) nasal swab (or respiratory sample, if hospitalized) positive for SARS-CoV-2 by NAAT. Because additional NAAT testing was performed at Month 1 for AG1 but not AG2-1, NAAT results at Month 1 were not considered. 3. The symptom date and NAAT positive date must be within 14 days of each other. The date of a COVID-19 endpoint according to the CDC-based definition is the earlier date of a symptom and the date of positive NAAT that satisfy the criteria stated above. The CDC criteria do not require adjudication.
Part A: Number of Participants With a First Occurrence of COVE-defined COVID-19 Starting 1 Day After Month 0 Dose Until Month 6 Dose in FAS Cohort Between Analysis Group 1 (AG1) and Analysis Group 2-1 (AG2-1
时间窗: 1 day after Month 0 dose until Month 6 dose
The COVE-based COVID-19 endpoint is defined as the first occurrence of adjudicated symptomatic NAAT-confirmed COVID-19 based on the following criteria (same as in the Moderna mRNA-1273 COVE trial): 1. At least TWO of the following systemic symptoms: Fever ≥ 38◦C), chills, myalgia, headache, sore throat, new loss of taste or smell, OR 2. At least ONE of the following respiratory signs/symptoms: cough, shortness of breath or difficulty breathing, OR clinical or radiographical evidence of pneumonia, AND 3. At least ONE (post-baseline) nasal swab (or respiratory sample, if hospitalized) positive for SARS-CoV-2 by NAAT. The date of a COVID-19 endpoint is the later date of a symptom and the date of positive NAAT. The COVE criteria require adjudication.
Part A: Number of Participants With a First Occurrence of COVE-based Severe COVID-19 Starting 1 Day After Month 0 Dose Until Month 6 Dose in FAS Between Analysis Group 1 (AG1) and Analysis Group 2-1 (AG2-1)
时间窗: 1 day after Month 0 dose until Month 6 dose
The COVE-based severe COVID-19 endpoint is defined as the first occurrence of a confirmed case of COVE-based COVID-19, plus any of the following: 1. Clinical signs indicative of severe systemic illness, Respiratory Rate ≥ 30 per minute, Heart Rate ≥ 125 beats per minute, SpO2 ≤ 93% on room air at sea level or PaO2/FIO2 less than 300 mm Hg, OR 2. Respiratory failure or Acute Respiratory Distress Syndrome (ARDS), (defined as needing high-flow oxygen, noninvasive or mechanical ventilation, or ECMO), evidence of shock (systolic blood pressure less than 90 mmHg, diastolic BP less than 60 mmHg or requiring vasopressors), OR 3. Significant acute renal, hepatic, or neurologic dysfunction, OR 4. Admission to an intensive care unit or death. The severe COVE criteria require adjudication.
Part B: Number of Participants With a First Occurrence of CDC-based COVID-19 Starting 14 Days After Month 6 Dose Until End of Follow up in RM6 Cohort Between Month 6 Monovalent and Bivalent Boost Groups
时间窗: 14 days after Month 6 dose until end of follow up (up to 18 months)
The CDC-based COVID-19 endpoint is defined as the first occurrence of symptomatic NAAT-confirmed COVID-19 based on the following criteria: 1. At least ONE of the following systemic or respiratory symptoms: Fever (≥ 38C), chills, cough, shortness of breath and/or difficulty breathing, fatigue, muscle and/or body aches \[not related to exercise\], headache, new loss of taste/smell, sore throat, congestion, runny nose, nausea, vomiting, or diarrhea, AND 2. At least ONE (post-baseline) nasal swab (or respiratory sample, if hospitalized) positive for SARS-CoV-2 by NAAT. 3. The symptom date and NAAT positive date must be within 14 days of each other. The date of a COVID-19 endpoint according to the CDC-based definition is the earlier date of a symptom and the date of positive NAAT that satisfy the criteria stated above. The CDC criteria do not require adjudication.
Part B: Number of Participants With a First Occurrence of COVE-based COVID-19 Starting 14 Days After Month 6 Dose Until End of Follow up in RM6 Cohort Between Month 6 Monovalent and Bivalent Boost Group
时间窗: 14 days after Month 6 dose until end of follow up (up to 18 months)
The COVE-based COVID-19 endpoint is defined as the first occurrence of adjudicated symptomatic NAAT-confirmed COVID-19 based on the following criteria (same as in the Moderna mRNA-1273 COVE trial): 1. At least TWO of the following systemic symptoms: Fever ≥ 38◦C), chills, myalgia, headache, sore throat, new loss of taste or smell, OR 2. At least ONE of the following respiratory signs/symptoms: cough, shortness of breath or difficulty breathing, OR clinical or radiographical evidence of pneumonia, AND 3. At least ONE (post-baseline) nasal swab (or respiratory sample, if hospitalized) positive for SARS-CoV-2 by NAAT. The date of a COVID-19 endpoint is the later date of a symptom and the date of positive NAAT. The COVE criteria require adjudication.
Part B: Number of Participants With a First Occurrence of COVE-based Severe COVID-19 Starting 14 Days After Month 6 Dose Until End of Follow up in RM6 Cohort Between Month 6 Monovalent and Bivalent Groups
时间窗: 14 days after Month 6 dose until end of follow up (up to 18 months)
Statistical analyses were not performed because there are fewer than 7 severe COVE-based severe COVID-19 starting 14 days after Month 6 dose until end of follow up in RM6 cohort.
Part A: Number of Participants With Solicited Adverse Events in the Safety Subset
时间窗: Up to 7 days following Month 0 vaccination (all Study Groups) and up to 7 days following Month 1 vaccination (Study Groups 1 and 3)
All solicited adverse events/reactogenicity symptoms are followed until resolution and graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, dated July 2017. Local reacto symptoms collected are: erythema/redness, induration/swelling, lymphadenopathy, and pain/tenderness. Systemic reacto symptoms collected are: arthralgia, chills, fever, headache, malaise/fatigue, myalgia, and nausea.
Part A: Number of Participants With Unsolicited Adverse Events in the Safety Subset
时间窗: Up to 28 days following Month 0 vaccination (all Study Groups) and up to 28 days following Month 1 vaccination (Study Groups 1 and 3)
All unsolicited AEs are graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017.
Part B: Number of Participants With Unsolicited Adverse Events in the Safety Subset
时间窗: Up to 28 days following Month 6 vaccination
All unsolicited AEs are graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017.
Part A: Number of Participants With Serious Adverse Events (SAEs)
时间窗: Up to Month 6
An SAE is any AE that results in any of the following outcomes: death, a life-threatening adverse event, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, congenital anomaly/birth defect, or is medically important.
Part B: Number of Participants With Serious Adverse Events (SAEs)
时间窗: Day of Month 6 vaccination up to Month 18
An SAE is any AE that results in any of the following outcomes: death, a life-threatening adverse event, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, congenital anomaly/birth defect, or is medically important.
Part A: Number of Participants With Adverse Events of Special Interest (AESIs)
时间窗: Up to Month 6
Adverse events of special interest (AESI) were described in Appendix L of the protocol. AESI for this protocol include but are not limited to potential immune-mediated diseases.
Part B: Number of Participants With Adverse Events of Special Interest (AESIs)
时间窗: Day of Month 6 vaccination up to Month 18
Adverse events of special interest (AESI) were described in Appendix L of the protocol. AESI for this protocol include but are not limited to potential immune-mediated diseases.
次要结局
- Part A: Number of Participants With First CDC-based COVID-19 Occurrence From 1 Day After Month 0 Dose to Month 6 Dose in FAS Cohort, Comparing Baseline SARS-CoV-2 Negative vs Positive, Regardless of HIV Status(1 day after Month 0 dose until Month 6 dose)
- Part A: Number of Participants With First COVE-based COVID-19 Occurrence From 1 Day After Month 0 Dose to Month 6 Dose in FAS Cohort, Comparing Baseline SARS-CoV-2 Negative vs Positive, Regardless of HIV Statu(1 day after Month 0 dose until Month 6 dose)
- Part A: Number of Participants With First COVE-based Severe COVID-19 Occurrence From 1 Day After Month 0 Dose to Month 6 Dose in FAS Cohort, Comparing Baseline SARS-CoV-2 Negative vs Positive, Regardless of HI(1 day after Month 0 dose until Month 6 dose)
- Part B: Number of Participants With a First Occurrence of CDC-based COVID-19 Starting 14 Days After Month 6 Dose Until End of Follow up in RM6 Cohort Who Have Month 6 Hybrid Immunity Between Month 6 Monovalent and Bivalent Boost Groups(14 days after Month 6 dose until end of follow up (up to 18 months))
- Part B: Number of Participants With a First Occurrence of CDC-based COVID-19 Starting 14 Days After Month 6 Dose Until End of Follow up in RM6 Cohort Who Have Month 6 Vaccine Immunity Between Month 6 Monovalent and Bivalent Boost Group(14 days after Month 6 dose until end of follow up (up to 18 months))
- Part A: Geometric Mean Titers (GMTs) of SARS-CoV-2 Antibodies as Measured by Neutralizing Antibody (NAb) Assay(Month 0, 4 weeks post final pre-Month 6 vaccination (peak timepoint))
- Part A: Geometric Mean Titers (GMTs) of SARS-CoV-2 Antibodies as Measured by Meso Scale Discovery-electrochemiluminescence Assay (MSD-ECL)(Month 0, 4 weeks post final pre-Month 6 vaccination (peak timepoint))
- Part A: Geometric Mean Titers of T-Cell Responses as Measured by Intracellular Cytokine Staining (ICS) Assay at Month 0(Month 0)
- Part A: Geometric Mean Titers of T-Cell Responses as Measured by Intracellular Cytokine Staining (ICS) Assay at Peak Timepoint(4 weeks post final pre-Month 6 vaccination (peak timepoint))
- Part B: Geometric Mean Titers (GMTs) of SARS-CoV-2 Antibodies as Measured by Neutralizing Antibody Assay(Months 6 and 7)
- SARS-CoV-2 Viral Persistence and Evolution Among Participants Virologically Diagnosed With SARS-CoV-2(Participants testing positive for SARS-CoV-2 had additional nasab swabs taken fortnightly until testing negative, up to a maximum of 18 months)