An Open-label, Phase 2 Study to Evaluate the Safety, Reactogenicity, and Immunogenicity of Ad26.COV2.S in Healthy Pregnant Participants
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 51
- 试验地点
- 17
- 主要终点
- Number of Adult Participants With Solicited Local Adverse Events (AEs) for 7 Days Post First Vaccination
研究概览
简要总结
The purpose of this study is to assess the safety and reactogenicity of Ad26.COV2.S administered intramuscularly (IM) as a 1-dose schedule at the standard dose level in adult participants during the second and/or third trimester of pregnancy and (potentially) post-partum; to assess the humoral immune response in peripheral blood of adult participants to Ad26.COV2.S administered IM as a 1-dose schedule during the second and/or third trimester of pregnancy, 28 days after vaccination.
详细描述
There is an increased risk of severe coronavirus disease-2019 (COVID-19) during pregnancy, as well as an increased risk of adverse birth outcomes. Therefore, the aim of this study is to assess the safety, reactogenicity and immunogenicity of Ad26.COV2.S in adult participants in the second and/or third trimester of pregnancy. Ad26.COV2.S (also known as Ad26COVS1) is a monovalent vaccine composed of a recombinant, replication incompetent adenovirus type 26 (Ad26) vector, constructed to encode the S protein derived from a severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) clinical isolate, stabilized in its prefusion conformation. For each adult participant, the total study duration from screening until the last follow-up visit will be approximately 16 months. The study will consist of a screening phase (28 days), vaccination period (study period from vaccination to pregnancy completion/termination) and a follow-up period (up to 12 months post pregnancy completion/termination). For neonates/infants born to the participants in the study will be followed for approximately 12 months postpartum. Safety assessments will include immunogenicity assessments, physical examination, vital signs, clinical safety laboratory assessments, medical, obstetric and delivery history, pregnancy outcome, neonate safety assessment, adverse events (AEs), serious adverse events (SAEs), and adverse events of special interest (AESI).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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 45 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •If on medication for a condition, the medication dose must have been stable for at least 4 weeks preceding vaccination
- •Participant must be healthy as confirmed by medical history, physical examination, vital signs, and obstetric history performed at Screening. Participant may have underlying illnesses, as long as the symptoms and signs are medically controlled
- •Participant will be at second or third trimester of pregnancy, that is, Week 16 to Week 38 of gestation (inclusive), at the time of vaccination, based on ultrasound at the time of screening (or not longer than 10 days prior to vaccination if performed elsewhere)
- •Participant agrees to not donate bone marrow, blood, and blood products from the first study vaccine administration until 3 months after receiving the last dose of study vaccine
- •Participant must be willing to provide verifiable identification, has means to be contacted and to contact the investigator during the study
- •Participant either received their last COVID-19 vaccination with an authorized/licensed COVID-19 vaccine (at least 4 months prior to first study vaccination) or is COVID 19 vaccine-naïve
排除标准
- •Participants with medical or obstetric histories that put them at higher risk for maternal or fetal complications (example, chronic pregnancy-related disorders, birth defects or genetic conditions during previous pregnancy)
- •Participant with abnormal pregnancy screening test (example, ultrasound fetal abnormalities, maternal blood screen)
- •Participant has a history of malignancy within 2 years before screening (exceptions are squamous, basal cell carcinomas of the skin, carcinoma in situ of the cervix, or malignancy, considered cured with minimal risk of recurrence)
- •Participant has a known or suspected allergy or history of anaphylaxis or other serious adverse reactions to vaccines or their excipients (including specifically the excipients of the study vaccine)
- •Participant has a history of any serious, chronic, or progressive neurological disorders or seizures including Guillain-Barre syndrome, with the exception of febrile seizures during childhood
- •Participant has a positive diagnostic test result (polymerase chain reaction [PCR] based viral ribonucleic acid [RNA] detection) severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection at screening or Day 1 (if more than 4 days in between)
- •Participant has a history of thrombosis with thrombocytopenia syndrome (TTS), including cerebral venous sinus thrombosis (CVST), or heparin-induced thrombocytopenia (HIT)
- •Participant has a history of capillary leak syndrome (CLS)
研究组 & 干预措施
Groups 1-4: Ad26.COV2.S (One Dose)
Participants who are previously vaccinated (Group 1-3) and participants who are vaccine naïve (Group 4) will receive single dose of Ad26.COV2.S vaccine at standard dose level on Day 1. Participants from group 4 who are no longer pregnant may receive single booster dose of Ad26.COV2.S vaccine at standard dose level.
干预措施: Ad26.COV2.S (Biological)
结局指标
主要结局
Number of Adult Participants With Solicited Local Adverse Events (AEs) for 7 Days Post First Vaccination
时间窗: From first vaccination on Day 1 up to 7 days post first vaccination (up to Day 8)
Number of adult participants with solicited local AEs for 7 days post first vaccination was reported. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. Solicited AEs were used to assess the reactogenicity of the study vaccine and were pre-defined as local (at the injection site) AEs for which participants were specifically asked and which were noted by participants in their reactogenicity diary for 7 days post first vaccination (day of first vaccination and the subsequent 7 days). Solicited local AEs are injection site pain/tenderness, erythema, swelling at the vaccination site.
Number of Adult Participants With Solicited Systemic AEs for 7 Days Post First Vaccination
时间窗: From first vaccination on Day 1 up to 7 days post first vaccination (up to Day 8)
Number of adult participants with solicited systemic AEs for 7 days post first vaccination was reported. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. Solicited AEs were used to assess the reactogenicity of the study vaccine and were predefined as systemic AEs for which participants were specifically asked and which were noted by participants in their reactogenicity diary for 7 days post first vaccination. Participants were instructed on how to note signs and symptoms in the diary on a daily basis for 7 days post first vaccination (day of first vaccination and the subsequent 7 days) for the following solicited systemic AEs: fatigue, headache, nausea, myalgia.
Number of Adult Participants With Unsolicited AEs for 28 Days Post First Vaccination
时间窗: From first vaccination on Day 1 up to 28 days post first vaccination (up to Day 29)
Number of adult participants with unsolicited AEs for 28 days post first vaccination was reported. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. Unsolicited AEs were defined as AEs for which the participants were not specifically questioned in the participant's reactogenicity diary.
Number of Adult Participants With Serious Adverse Events (SAEs) From First Vaccination Until End of the Study (EOS)
时间窗: From first vaccination on Day 1 until end of study (up to post-partum [PP] Day 366 [Day 15 up to Day 554])
Number of adult participants with SAEs from first vaccination until EOS were reported. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. SAEs were defined as any untoward medical occurrence that at any dose results in any of the following outcomes: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly/birth defect; suspected transmission of any infectious agent via a medicinal product or medically important.
Number of Adult Participants With Adverse Events of Special Interest (AESIs) From First Vaccination Until EOS
时间窗: From first vaccination on Day 1 until end of study (up to PP Day 366 [Day 15 up to Day 554])
Number of adult participants with AESIs from first vaccination until EOS were reported. Thrombosis with thrombocytopenia syndrome (TTS) in adults was considered an AESI in this study. TTS is a syndrome characterized by a combination of both a thrombotic event and thrombocytopenia.
Number of Adult Participants With Medically Attended Adverse Events (MAAEs) Until 6 Months Post First Vaccination
时间窗: From first vaccination on Day 1 until 6 months post first vaccination (up to Day 183)
Number of adult participants with MAAEs until 6 months post first vaccination was reported. MAAEs were defined as AEs with medically attended visits including hospital, emergency room, urgent care clinic, or other visits to or from medical personnel for any reason. Routine study visits were not considered medically attended visits. New onset of chronic diseases was collected as part of the MAAEs.
Number of Adult Participants With AEs Leading to Study Discontinuation
时间窗: From first vaccination on Day 1 until end of study (up to PP Day 366 [Day 15 up to Day 554])
Number of adult participants with AEs leading to study discontinuation were reported. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. All AEs leading to discontinuation from the study (regardless of the causal relationship) were reported for all adult participants from the moment of first vaccination until completion of the participant's last study-related procedure.
Serological Response to Vaccination as Measured by S-Enzyme-linked Immunosorbent Assay (S-ELISA) in Adult Participants 28 Days Post First Vaccination
时间窗: 28 days post first vaccination on Day 1 (at Day 29)
Serological response to vaccination as measured by S-ELISA in adult participants 28 days post first vaccination was reported.
次要结局
- Serological Response to First Vaccination as Measured by S-ELISA in Adult Participants at All Blood Collection Timepoints Post First Vaccination(Day 1, Day 29, PP Day 1 (Day 7 up to Day 163), PP Day 183 (Day 189 up to Day 345))
- Group 4: Number of Adult Participants With Solicited Local AEs for 7 Days Post Booster Vaccination(7 days post booster vaccination (Day 84 up to Day 371))
- Group 4: Number of Adult Participants With Solicited Systemic AEs for 7 Days Post Booster Vaccination(7 days post booster vaccination (Day 84 up to Day 371))
- Group 4: Number of Adult Participants With Unsolicited AEs for 28 Days Post Booster Vaccination(28 days post booster vaccination (Day 84 up to Day 392))
- Group 4: Number of Adult Participants With SAEs Post Booster Vaccination Until EOS(From booster vaccination (Day 84 up to Day 364) until EOS (up to PP Day 366 [Day 366 up to Day 554]))
- Group 4: Number of Adult Participants With AESIs Post Booster Vaccination Until EOS(From booster vaccination (Day 84 up to Day 364) until EOS (up to PP Day 366 [Day 366 up to Day 554]))
- Group 4: Number of Adult Participants With MAAEs Until 6 Months Post Booster Vaccination(6 months post booster vaccination (Day 84 up to Day 546))
- Group 4: Number of Adult Participants With AEs Leading to Study Discontinuation Post Booster Vaccination Until EOS(From post booster vaccination (Day 84 up to Day 364) until EOS (up to PP Day 366 [Day 366 up to Day 554]))
- Number of Adult Participants With Pregnancy Outcomes(From first vaccination on Day 1 until PP Day 1 (Day 7 up to Day 163))
- Number of Adult Participants With Pregnancy Related AEs Throughout Pregnancy(From first vaccination on Day 1 until PP Day 1 (Day 7 up to Day 163))
- Serological Response to First Vaccination as Measured by Virus Neutralization Assay (VNA) Titers, 28 Days in Adult Participants Post First Vaccination(28 days post first vaccination on Day 1 (at Day 29))
- Group 4: Serological Response to Booster Vaccination Measured by Binding (S-ELISA) Antibody Titers in Adult Participants at Blood Collection Time Points Post Booster Vaccination(Booster Day 1 (Day 84 up to Day 364), Booster Day 29 (Day 112 up to Day 392))
- Group 4: Serological Response to Booster Vaccination Measured by Neutralizing (VNA) Antibody Titers in Adult Participants at Blood Collection Time Points Post Booster Vaccination(Booster Day 1 (Day 84 up to Day 364), Booster Day 29 (Day 112 up to Day 392))
- Serological Response to Vaccination as Measured by S-ELISA at Birth (That is, in Cord Blood) and at 2 Months and 6 Months of Age in Neonates and Infants Born to Adult Participants(At birth (postnatal [PN] Day 1 [Day 7 up to Day 163]), 2 months (up to PN Day 61 [Day 67 up to Day 223]) and 6 months (up to PN Day 183 [Day 189 up to Day 345]))
- Serological Response to Vaccination as Measured by VNA Titers at Birth (That is, in Cord Blood) in Neonates and Infants Born to Adult Participants(At Birth (PN Day 1 [Day 7 up to Day 163]))
- Number of Neonates and Infants With SAEs (Including MIS-C) From Birth Up to 12 Months of Age in Neonates and Infants Born to Adult Participants(From birth (PN Day 1 [Day 7 up to Day 163]) up to 12 months of age (up to PN Day 366 [Day 372 up to Day 528]))
- Number of Neonates and Infants With AESIs From Birth Until 12 Months of Age in Neonates and Infants Born to Adult Participants(From birth (PN Day 1 [Day 7 up to Day 163]) until 12 months of age (up to PN Day 366 [Day 372 up to Day 528]))
- Number of Neonates and Infants With MAAEs From Birth Until 6 Months of Age in Neonates and Infants Born to Adult Participants(From birth (PN Day 1 [Day 7 up to Day 163]) until 6 months of age (up to PN 183 [Day 189 up to Day 345]))
- Number of Neonates and Infants With AEs Leading to Study Discontinuation From Birth Until Study Discontinuation(From birth (PN Day 1 [Day 7 up to Day 163]) until study discontinuation (until 12 months of age [up to PN Day 366 {Day 372 up to Day 528}]))
- Number of Neonates and Infants With Different Birth Outcomes From Birth Up to 12 Months of Age(From birth (PN Day 1 [Day 7 up to Day 163]) up to 12 months of age (up to PN Day 366 [Day 372 up to Day 528]))