A Phase 1/2 Study to Evaluate the Safety Reactogenicity and Immunogenicity of Ad26.COV2.S Administered as a Heterologous Booster Vaccination in Adults 18 Years of Age and Older Following Single- or Two-Dose Vaccination With an Inactivated COVID-19 Vaccine
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 690
- 试验地点
- 1
- 主要终点
- Frequency of solicited reportable local adverse event after vaccination
研究概览
简要总结
This study aims to address evidence gaps regarding the safety, reactogenicity and immune responses of a heterologous boost of a single dose of Ad26.COV2.S (half or full dose) at pre-specified time intervals in recipients who are documented to have received either 1-dose or 2-doses (primary series completion) of inactivated COVID-19 vaccines, Sinovac and/or Sinopharm.
详细描述
This is a prospective, multi-center, observer-blind Phase 1/2 adaptive study to assess the safety, reactogenicity, and immunogenicity of a booster dose of Ad26.COV2.S in adults ≥ 18 years of age in Study Part A and Part B. A total of 690 participants will be recruited. If the optional Group (A4) is feasible and enrolled, the total recruitment will be 800 participants. Priority enrolment is given to Groups A1 and A2, followed by Groups A3 and B1. Enrolment of groups are open-label allocation and assessor-masked.
The Study is divided into 2 Parts: Part A and B.
Study Part A is a prospective, multi-center, assessor-masked Phase 1/2 study to assess a booster dose (3rd dose) of Ad26.COV2.S as an IM injection in the deltoid muscle in adults who have completed the two-dose homologous primary series of inactivated vaccine of Sinovac or Sinopharm, 21 to 35 days apart and who meet eligibility criteria. Participants will receive either the full-dose (5x10^10 vp) or half-dose (2.5x10^10 vp) of the study product, and at early (45-75 days) or later (90-240 days) time interval and followed from Visit 1 (V1) to Visit 7 (V7) at 336 days.
A total of 580 adult volunteers aged 18 years or older, who have verified vaccination cards with documented completion of homologous primary vaccination series with either two doses of Adsorbed COVID-19 (inactivated) Sinovac (SV) or Sinopharm (SP) vaccine, against original and novel variants of SARS-CoV-2 will be enrolled. A 20% dropout rate is assumed. Enrolment is increased to 360 (300+20% dropout) for the safety assessment, to detect common adverse events with an event rate of 1%.
Part B is a prospective, multi-center, open-label, assessor-masked Phase 1/2 heterologous prime-boost study to assess the Ad26.COV2.S (full dose) as the 2nd vaccination in subjects who are documented to all have received the 1st dose of Sinovac or all received the 1st dose of Sinopharm COVID-19 vaccine, with an interval of 28 days or more, followed from Visit 1 (V1) to Visit 7 (V7) at 336 days.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Single (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
- 是
入选标准
- •Potential participants must meet all inclusion criteria to be enrolled and participate in the study, as follows:
- •Adult male or female aged 18 years or more on the day of signing the ICF, confirmed by identification cards.
- •Verified, documentation of past COVID-19 vaccination i. Study Part A: having completed the 2-dose homologous primary regimen (21 to 35 days apart) of inactivated COVID-19 vaccine of either Sinovac-Sinovac OR Sinopharm-Sinopharm ii. Study Part B: having received one dose of inactivated COVID-19 vaccine of either Sinovac or Sinopharm with the appropriate interval period
- •Women of childbearing potential who are test negative with a highly sensitive urine pregnancy test at Visit 1, prior to study vaccine administration.
- •Subject has provided written informed consent prior to performance of any study-specific procedures and is willing and has means to be contacted and to contact the investigator during the study.
- •In the investigator's clinical judgment, the participant is in good health, or has stable and well-controlled medical conditions.
- •Participant agrees to not donate bone marrow, blood, and blood products from the study vaccine administration until 3 months after receiving the study vaccine.
排除标准
- •Potential participants who meet any of the following exclusion criteria will be excluded from enrolment and participation in the study:
- •The participant has a clinically significant acute illness (this does not include minor illnesses such as diarrhea or mild upper respiratory tract infection), or is a patient under investigation (PUI) or has a body temperature ≥38.0ºC (100.4°F) within 24 hours prior to the planned study vaccination. Assignment may be made at a later date is permitted at the discretion of the investigator. Please notify the Sponsor (or medical monitor) of this decision.
- •Contraindication to Ad26.COV2.S according to labelling of the product. For example, if the 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;refer to the IB (IB Edition 5 Ad26.COV2.S 2021 and its addenda).
- •Pregnant or planning to become pregnant within 3 months after study vaccine administration
- •Participant has a history or current condition as follows
- •Known documented history of COVID-19 infection prior to enrollment
- •Any confirmed or suspected immunosuppressive or immunodeficient state.
- •Heparin-induced thrombocytopenia or thrombosis in combination with thrombocytopenia.
- •Acute polyneuropathy (e.g. Guillain-Barré syndrome).
- •Capillary leak syndrome
- •Contraindication to IM injections and blood draws e.g., bleeding disorders.
- •An underlying clinically significant acute or chronic medical condition or physical examination findings for which, in the opinion of the investigator, participation would not be in the best interest of the participant (e.g., compromise the well being) or that could prevent, limit, or confound the protocol-specified assessments.
- •Major psychiatric illness which in the investigator's opinion would compromise the participant's safety or compliance with the study procedures.
- •If the participant received or plans to receive:
- •Licensed live attenuated vaccines - within 28 days before or after planned administration of study vaccine.
- •Other licensed (not live) vaccines - within 14 days before or after planned administration of study vaccine.
- •Treatment with immunoglobulins (Ig) in the 3 months or exogenous blood products (autologous blood transfusions are not exclusionary) in the 4 months before the planned administration of the study vaccine or has any plans to receive such treatment during the study.
- •If the participant cannot communicate reliably with the investigator, or, in the opinion of the investigator, is unlikely to adhere to the requirements of the study or is unlikely to complete the full course of vaccination and observation.
- •Employee of the study center directly involved with the proposed study or with study investigators.
研究组 & 干预措施
Ad26.COV2.S given at the interval ≥ 90 days after completing 2 doses of either Sinovac or Sinopharm
Study Part A is a prospective, multi-center, Phase 2 study to assess a booster dose (3rd dose) of Ad26.COV2.S as an IM injection in the deltoid muscle in adults who have completed the two-dose homologous primary series of inactivated vaccine of Sinovac or Sinopharm, 21 to 35 days apart and who meet eligibility criteria.
In study part A1, a total of 360 adult volunteers aged 18 years or older, will receive the full-dose (5x10^10 vp) of the study product, at later (90 days or more) time interval since the 2nd dose and followed from Visit 1 (V1) to Visit 7 (V7) at 336 days.
干预措施: Full dose of Ad26.COV2. 5x10^10vp (Biological)
Ad26.COV2.S given at 45-75 days after completing 2 doses of either Sinovac or Sinopharm
Study Part A is a prospective, multi-center, Phase 2 study to assess a booster dose (3rd dose) of Ad26.COV2.S as an IM injection in the deltoid muscle in adults who have completed the two-dose homologous primary series of inactivated vaccine of Sinovac or Sinopharm, 21 to 35 days apart and who meet eligibility criteria.
In study part A2, a total of 110 adult volunteers aged 18 years or older, will receive the full-dose (5x10^10 vp) of the study product, at early (45-75 days) time interval since the 2nd dose and followed from Visit 1 (V1) to Visit 7 (V7) at 336 days.
干预措施: Full dose of Ad26.COV2. 5x10^10vp (Biological)
Half dose of Ad26.COV2.S given ≥ 90 days after completing 2 doses of either Sinovac or Sinopharm
Study Part A is a prospective, multi-center, Phase 2 study to assess a booster dose (3rd dose) of Ad26.COV2.S as an IM injection in the deltoid muscle in adults who have completed the two-dose homologous primary series of inactivated vaccine of Sinovac or Sinopharm, 21 to 35 days apart and who meet eligibility criteria.
In study part A3, a total of 110 adult volunteers aged 18 years or older, will receive the half-dose (2.5x10^10 vp) of the study product, at later (90 days or more) time interval since the 2nd dose and followed from Visit 1 (V1) to Visit 7 (V7) at 336 days.
干预措施: Half dose of Ad26.COV2. 2.5x10^10vp (Biological)
Ad26.COV2.S given 28 days after receiving 1 dose of either Sinovac or Sinopharm
Study Part B is a prospective, multi-center, open-label Phase 1/2 heterologous prime-boost study to assess the Ad26.COV2.S (full dose 5x10^10 vp) as the 2nd vaccination in subjects who are documented to all have received the 1st dose of Sinovac or all received the 1st dose of Sinopharm COVID-19 vaccine, with an interval of 28 days +/- 3 days, followed from Visit 1 (V1) to Visit 7 (V7) at 336 days.
干预措施: Full dose of Ad26.COV2. 5x10^10vp (Biological)
结局指标
主要结局
Frequency of solicited reportable local adverse event after vaccination
时间窗: Day 0 through Day 7
Frequency and percentage of solicited reportable local adverse events (pain or tenderness, erythema, swelling or induration) of vaccination
Frequency of solicited reportable systemic adverse event after vaccination
时间窗: Day 0 through Day 7
Frequency and percentage of solicited reportable systemic adverse events (fever, headache, fatigue or malaise, myalgia, arthralgia, nausea or vomitting) of vaccination
Frequency of all unsolicited AEs
时间窗: : Day 0 through Day 336
Frequency and percentage of all unsolicited AEs
GMT Anti-S IgG at baseline
时间窗: Day 0
GMT Anti-S IgG at baseline
GMT Anti-S IgG at 336 days after vaccination
时间窗: Day 336
GMT Anti-S IgG at 336 days after vaccination
GMT Anti-S IgG at 7 days after vaccination in subset subjects
时间窗: Day 7
GMT Anti-S IgG at 7 days after vaccination in subset subjects
GMT Anti-S IgG at 14 days after vaccination in subject subjects
时间窗: Day 14
GMT Anti-S IgG at 14 days after vaccination in subset subjects
GMT Anti-S IgG at 28 days after vaccination
时间窗: Day 28
GMT Anti-S IgG at 28 days after vaccination
GMT Anti-S IgG at 84 days after vaccination
时间窗: Day 84
GMT Anti-S IgG at 84 days after vaccination
GMT Anti-S IgG at 168 days after vaccination
时间窗: Day 168
GMT Anti-S IgG at 168 days after vaccination
GMFR changed from baseline in anti-S IgG GMT at 28 days after vaccination
时间窗: Day 28
GMFR changed from baseline in anti-S IgG GMT at 28 days vaccination
GMFR changed from baseline in anti-S IgG GMT at 84 days after vaccination
时间窗: Day 84
GMFR changed from baseline in anti-S IgG GMT at 84 days vaccination
GMFR changed from baseline in anti-S IgG GMT at 168 days after vaccination
时间窗: Day 168
GMFR changed from baseline in anti-S IgG GMT at 168 days vaccination
GMFR changed from baseline in anti-S IgG GMT at 336 days after vaccination
时间窗: Day 336
GMFR changed from baseline in anti-S IgG GMT at 336 days vaccination
Anti-S IgG Seroresponses changed from baseline at 28 days after vaccination
时间窗: Day 28
Frequency and percentage of participants with seroresponses in anti-S IgG titer as defined by (1) a ≥ 4-fold increase from baseline at 28 days after vaccination
Anti-S IgG Seroresponses changed from baseline at 84 days after vaccination
时间窗: Day 84
Frequency and percentage of participants with seroresponses in anti-S IgG titer as defined by (1) a ≥ 4-fold increase from baseline at 84 days after vaccination
Anti-S IgG Seroresponses changed from baseline at 168 days after vaccination
时间窗: Day 168
Frequency and percentage of participants with seroresponses in anti-S IgG titer as defined by (1) a ≥ 4-fold increase from baseline at 168 days after vaccination
Anti-S IgG Seroresponses changed from baseline at 336 days after vaccination
时间窗: Day 336
Frequency and percentage of participants with seroresponses in anti-S IgG titer as defined by (1) a ≥ 4-fold increase from baseline at 336 days after vaccination
次要结局
- GMT measured by pseudovirus neutralization assay (pNA) and microneutralization assay (mNA) Neutralizing antibody titer 50 at baseline(Day 0)
- GMT measured by pseudovirus neutralization assay (pNA) and microneutralization assay (mNA) Neutralizing antibody titer 50 at 28 days after Ad26.COV2.S vaccination(Day 28)
- GMT measured by pseudovirus neutralization assay (pNA) and microneutralization assay (mNA) Neutralizing antibody titer 50 at 84 days after Ad26.COV2.S vaccination(Day 84)
- GMT measured by pseudovirus neutralization assay (pNA) and microneutralization assay (mNA) Neutralizing antibody titer 50 at 168 days after Ad26.COV2.S vaccination(Day 168)
- GMT measured by pseudovirus neutralization assay (pNA) and microneutralization assay (mNA) Neutralizing antibody titer 50 at 336 days after Ad26.COV2.S vaccination(Day 336)
- GMFR changed from baseline (pre-boost titer) in NT50 measured by pNA and mNA against SARS-CoV-2 Delta and Wildtype at 28 days after Ad26.COV2.S vaccination(Day 336)
- GMFR changed from baseline (pre-boost titer) in NT50 measured by pNA and mNA against SARS-CoV-2 Delta and Wildtype at 84 days after Ad26.COV2.S vaccination(Day 84)
- GMFR changed from baseline (pre-boost titer) in NT50 measured by pNA and mNA against SARS-CoV-2 Delta and Wildtype at 28 days after Ad26.COV2.S vaccination(Day 28)
- GMFR changed from baseline (pre-boost titer) in NT50 measured by pNA and mNA against SARS-CoV-2 Delta and Wildtype at 28 days after Ad26.COV2.S vaccination(Day 168)