NCT06615375进行中（未招募）2 期
Phase 2b, Double-blind, Placebo-controlled Efficacy Challenge Study With the Shigella Tetravalent Bioconjugate Vaccine Shigella4V2
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 120
- 试验地点
- 3
- 主要终点
- To demonstrate that the Shigella4V2 bioconjugate vaccine protects against shigellosis following challenge with the wild type S. sonnei 53G strain.
研究概览
简要总结
In this challenge study, the bioconjugate candidate vaccine Shigella4V2 will be tested for its ability to induce an immune response that protects healthy adult volunteers from infection with a wild-type Shigella sonnei strain compared to participants receiving placebo.
详细描述
The tetravalent Shigella4V2 bioconjugate vaccine candidate will be tested for safety and preliminary efficacy in a Phase 2b controlled human infection model (CHIM) study at three sites in the United States. This trial will be conducted as a parallel-group, randomized, double-blind, multicenter, placebo-controlled study to evaluate the safety, immunogenicity, and efficacy of two injections of Shigella4V2 in healthy Shigella naïve participants 18-50 years of age, with the second injection administered one month before challenge with S. sonnei 53G strain. It will have two steps:
- Step 1, a dose confirmation step, in which a first injection of Shigella4V2 (high dose or low dose, adjuvanted with Alhydrogel) will be administered alongside a placebo arm (phosphate-buffered saline) at a ratio of 2:2:1. A second injection of either Shigella4V2 low dose or placebo will be administered about 6 months after the first injection.
- Step 2, in which participants will be randomized to the Shigella4V2 dose selected after Step 1 or to placebo at a ratio of 1:1. Participants will receive two injections, 28 days apart. One month after the second injection, they will be challenged with 1500 CFU of the virulent Shigella sonnei strain 53G.
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 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Step 1 and Step 2:
- •Age 18-50 years (inclusive).
- •In good health and stable medical condition, determined by MH, laboratory results, and physical examination during screening period.
- •Negative pregnancy test at the time of 1st injection, for participants of childbearing potential.
- •Persons of childbearing potential must agree to avoid pregnancy by use of effective contraception for 30 days prior to 1st injection and throughout the study. Participants assigned female at birth and unable to bear children must have this documented (e.g., tubal ligation or hysterectomy).
- •Willingness to participate in the study after all aspects of the protocol have been explained and written informed consent obtained.
- •Availability for the study duration, including all planned follow-up visits and phone calls.
- •Willingness to refrain from participating in other studies of investigational products until completion of the last study contact.
- •Step 2 only:
- •Demonstrated comprehension of the protocol procedures, knowledge of Shigella- associated illness, and passing score of 70% or better on a comprehension assessment. Maximum two attempts are allowed.
排除标准
- •Step 1 and Step 2:
- •Participants currently pregnant, lactating, or intending to become pregnant during the study period as reported by the participant.
- •Presence of a significant medical or psychiatric condition which in the opinion of the investigator precludes participation in the study.
- •Clinically significant abnormalities in vital signs or in screening hematology / blood chemistry as determined by the investigator.
- •Presence in the serum of HIV 1/2 antibody, HBs-Ag, or HCV antibody (if confirmed positive by Hepatitis C confirmatory test, i.e., recombinant immunoblot assay (RIBA), polymerase chain reaction (PCR)).
- •Evidence of current excessive alcohol consumption or drug dependence (e.g. according to medical history).
- •Known or suspected impairment of immunological function (e.g., documented HIV infection, asplenia/splenectomy, or history of autoimmune disease or lymphoproliferative disorder).
- •BMI < 19 or > 35 kg/m
- •Recent vaccination or planned vaccination within 14 days of 1st study injection for inactivated vaccines and within 30 days for live vaccines.
- •Recent receipt of an investigational product within 30 days preceding the 1st study injection or planned during the entire study period.
- •Recent treatment with immunoglobulins or blood products within 3 months preceding the 1st study injection or planned use during the entire study period.
- •Use of any medication known to affect the immune function (e.g., systemic steroids) within 30 days preceding the 1st study injection or planned use during the entire study period.
- •Symptoms consistent with Traveler's Diarrhea concurrent with travel to countries where Shigella infection is endemic (most of the developing world).
- •Vaccination for or ingestion of Shigella.
- •Use of systemic antibiotics during the 7 days before 1st injection.
- •Serum IgG titers to S. sonnei LPS ≥
- •Current occupation involving the handling of Shigella bacteria.
- •History of allergy to components of the study vaccine (Alhydrogel), to placebo (PBS), or to soy, or any other allergy the investigator deems to increase their risk of AEs in the study.
- •Any other criteria which, in the investigator's opinion, would compromise the ability of the participant to participate in the study, the safety of the study, or the results of the study.
- •Part of study personnel or close family member of personnel conducting the study.
- •Step 2 only:
- •Personal history of inflammatory ReA.
- •Positive blood test for HLA-B27 antigen.
- •Personal history of IBS as defined by Rome IV criteria.
- •Regularly abnormal stool pattern (fewer than 3 per week or more than 3 per day).
- •Regular use of laxatives, antacids, or other agents to lower stomach acidity.
- •Known allergy to challenge agent components.
- •Known allergy to ciprofloxacin or trimethoprim-sulfamethoxazole.
- •Evidence of IgA deficiency (serum IgA < 7 mg/dL or limit of detection of assay).
- •Planning to travel to Shigella endemic countries before completion of the challenge phase of the study.
- •Personal history of inflammatory bowel disease.
研究组 & 干预措施
Shigella4V2 High dose
Experimental
1 injection of high dose Shigella4V2 and 1 injection of low dose Shigella4V2 will be injected intramuscularly in the deltoid muscle
干预措施: Shigella4V2 (Biological)
Shigella4V2 Low dose
Experimental
2 injections of low dose of Shigella4V2 will be injected intramuscularly in the deltoid muscle
干预措施: Shigella4V2 (Biological)
Placebo
Placebo Comparator
2 injections of PBS will be injected intramuscularly in the deltoid muscle
干预措施: Placebo (Biological)
结局指标
主要结局
To demonstrate that the Shigella4V2 bioconjugate vaccine protects against shigellosis following challenge with the wild type S. sonnei 53G strain.
时间窗: To be evaluated post-challenge during the inpatient period (Day 56 through Day 65) in vaccinees vs. placebo
The number of challenged participants with shigellosis post-challenge during the inpatient period that received vaccine compared to participants who received placebo. Shigellosis is defined as: 1. Severe diarrhea; OR 2. Moderate diarrhea AND \[fever OR ≥ 1 at least moderate constitutional/enteric symptoms OR ≥ 2 episodes of vomiting in 24 h\]; OR 3. Dysentery AND \[fever OR ≥ 1 at least moderate constitutional/enteric symptoms OR ≥ 2 episodes of vomiting in 24 h\]
次要结局
- Efficacy - Number of participants with severe constitutional enteric symptoms(To be evaluated post-challenge during the inpatient period (Day 56 through Day 65) in vaccine responders vs. placebo as well as vaccinees vs. placebo)
- Efficacy - Number of participants with fever(To be evaluated post-challenge during the inpatient period (Day 56 through Day 65) in vaccine responders vs. placebo as well as vaccinees vs. placebo)
- Efficacy - Highest recorded temperature(To be evaluated post-challenge during the inpatient period (Day 56 through Day 65) in vaccine responders vs. placebo as well as vaccinees vs. placebo)
- Efficacy - Number of participants with blood in stool as confirmed by hemoccult(To be evaluated post-challenge during the inpatient period (Day 56 through Day 65) in vaccinees vs. placebo)
- Efficacy - Number of participants with moderate-to-severe shigellosis(To be evaluated post-challenge during the inpatient period (Day 56 through Day 65) in vaccine responders vs. placebo as well as vaccinees vs. placebo)
- Efficacy - Number of participants with diarrhea of any severity(To be evaluated post-challenge during the inpatient period (Day 56 through Day 65) in vaccine responders vs. placebo as well as vaccinees vs. placebo)
- Efficacy - Number of participants with severe diarrhea(To be evaluated post-challenge during the inpatient period (Day 56 through Day 65) in vaccine responders vs. placebo as well as vaccinees vs. placebo)
- Efficacy - Number of participants with moderate or severe diarrhea(To be evaluated post-challenge during the inpatient period (Day 56 through Day 65) in vaccine responders vs. placebo as well as vaccinees vs. placebo)
- Efficacy - Number of participants with more severe diarrhea(To be evaluated post-challenge during the inpatient period (Day 56 through Day 65) in vaccine responders vs. placebo as well as vaccinees vs. placebo)
- Efficacy - Maximum weight of grade 3-5 stools passed in 24 h per participant(To be evaluated post-challenge during the inpatient period (Day 56 through Day 65) in vaccine responders vs. placebo as well as vaccinees vs. placebo)
- Efficacy - Maximum number of grade 3-5 stools passed in 24 h per participant(To be evaluated post-challenge during the inpatient period (Day 56 through Day 65) in vaccine responders vs. placebo as well as vaccinees vs. placebo)
- Efficacy - Number of participants with moderate or severe constitutional enteric symptoms(To be evaluated post-challenge during the inpatient period (Day 56 through Day 65) in vaccine responders vs. placebo as well as vaccinees vs. placebo)
- Efficacy - Time from challenge to onset of diarrhea(To be evaluated post-challenge during the inpatient period (Day 56 through Day 65) in vaccine responders vs. placebo as well as vaccinees vs. placebo)
- Efficacy - Time from challenge to onset of shigellosis(To be evaluated post-challenge during the inpatient period (Day 56 through Day 65) in vaccine responders vs. placebo as well as vaccinees vs. placebo)
- Efficacy - Duration of diarrhea(To be evaluated post-challenge during the inpatient period (Day 56 through Day 65) in vaccine responders vs. placebo as well as vaccinees vs. placebo)
- Efficacy - Shigella disease severity score(To be evaluated post-challenge during the inpatient period (Day 56 through Day 65) in vaccine responders vs. placebo as well as vaccinees vs. placebo)
- Efficacy - Number of participants requiring early antibiotic therapy(To be evaluated post-challenge during the inpatient period (Day 56 through Day 65) in vaccine responders vs. placebo as well as vaccinees vs. placebo)
- Efficacy - Number of participants requiring IV fluids(To be evaluated post-challenge during the inpatient period (Day 56 through Day 65) in vaccine responders vs. placebo as well as vaccinees vs. placebo)
- Safety - Solicited Local and Systemic Adverse Events (AEs)(To be evaluated after injection in vaccinees vs. placebo during the 7-day follow-up period of each injection (day of administration and 6 following days))
- Safety - Unsolicited AEs(To be evaluated after injection in vaccinees vs. placebo during the 28-day follow-up period after each injection (day of administration and 27 following days))
- Safety - All Solicited and Unsolicited AEs post-injection(To be evaluated after injection in vaccinees vs. placebo during the 28-day follow-up period after each injection (day of administration and 27 following days))
- Safety - Unsolicited AEs post-challenge(To be evaluated after challenge in vaccinees vs. placebo during the 28-day follow-up period post-challenge (day of challenge and 27 following days))
- Safety - Medically relevant AEs post-injection(To be evaluated in vaccinees vs. placebo from 28 days post each injection until receipt of next injection, challenge, or until their study end)
- Safety - Medically relevant AEs post-challenge(To be evaluated in vaccinees vs. placebo from 28 days post-challenge (Day 57) until their study end)
- Safety - Serious Adverse Events (SAEs)(To be evaluated after injection in vaccinees vs. placebo until their study end)
- Safety - AEs leading to withdrawal from the trial(To be evaluated after injection in vaccinees vs. placebo until their study end)
- Safety - Evaluate changes in hematological and blood chemistry parameters following injection(To be evaluated at 7-days of each post-injection compared to baseline values in vaccinees vs. placebo)
- Immunogenicity - Geometric mean titers (GMTs) of anti-S. sonnei LPS IgGs in serum(To be evaluated in vaccinees vs. placebo from Day 1 until study end)
- Immunogenicity - GMTs of anti-S. flexneri 2a LPS IgGs in serum(To be evaluated in vaccinees vs. placebo from Day 1 until study end)
- Immunogenicity - GMTs of anti-S. flexneri 3a LPS IgGs in serum(To be evaluated in vaccinees vs. placebo from Day 1 until study end)
- Immunogenicity - GMTs of anti-S. flexneri 6 LPS IgGs in serum(To be evaluated in vaccinees vs. placebo from Day 1 until study end)
- Immunogenicity - establish or confirm immunomarker that correlate with a reduced risk of shigellosis(To be evaluated in challenged vaccinees from Day 1 to Day 65)
- Immunogenicity - establish or confirm immunomarker that correlate with a reduced risk of moderate-to-severe shigellosis(To be evaluated in challenged vaccinees from Day 1 to Day 65)
- Immunogenicity - establish or confirm immunomarker that correlate with a reduced risk of solicited events(To be evaluated in challenged vaccinees from Day 1 to Day 65)
- The number of challenged participants with shigellosis post-challenge during the inpatient period that responded to Shigella4V2 vaccine compared to participants who received placebo.(To be evaluated post-challenge during the inpatient period (Day 56 through Day 65) in vaccine responders vs. placebo)
研究者
研究点 (3)
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