跳至主要内容
MedPath Trial logoMedPath TrialMedPath Trial Home
临床试验/NCT02934178
NCT02934178已完成1 期

A Phase 1 Randomized, Double-Blinded, Placebo-controlled, Dose-Escalation Study to Assess the Safety, Tolerability and Immunogenicity of Live Attenuated, Oral Shigella WRSS1 Vaccine in Bangladeshi Toddlers (12 to 24 Months Old)

PATH1 个研究点 分布在 1 个国家目标入组 16 人开始时间: 2017年2月23日最近更新:
Share to TwitterShare to FacebookShare to LinkedInShare to Reddit
适应症

试验速览

阶段
1 期
状态
已完成
发起方
入组人数
16
试验地点
1
主要终点
Maximum Severity of Reactogenicity by Vaccination
研究概览研究设计入排标准结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

This is a research study of an experimental (investigational) live attenuated Shigella sonnei vaccine (WRSS1) to find a dose of the vaccine that is safe, tolerable, and develops an immune response. Shigella causes bloody and watery diarrhea, and infants and children living in developing countries experience the greatest consequences of this disease.

详细描述

The WRSS1 vaccine in will be given to healthy toddlers (12-24 months old). The first vaccination was given to toddlers in the inpatient unit and the second and third doses will be administered on an outpatient basis. A safety evaluation was performed after the first dose before enrolling subjects in subsequent cohorts to receive a higher vaccine dose.

After the study was initiated, its funder, the Bill and Melinda Gates Foundation (BMGF) made significant changes to the PATH Enteric Vaccine Initiative (EVI) portfolio and decided not to support the three higher-dose cohorts (Cohort 1, 2, and 3) planned as part of this study.

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
12 Months 至 24 Months（Child）
性别
All
接受健康志愿者
是

入选标准

  • •Male or female children aged between 12 to 24 month of age at the time of vaccination
  • •General good health as determined by the screening evaluation no greater than 30 days before admission
  • •Father, mother or other legally acceptable representative (guardian) properly informed about the study, able to understand it and sign the informed consent form
  • •Normal bowel habits (< 3 grade 1 or 2 stools each day; ≥ 1 grade 1 or 2 stools every 2 days)
  • •Free of obvious health problems as established by medical history and clinical examination before entering into the study.
  • •Parent or guardian available for the entire period of the study and reachable by study staff throughout the entire follow-up period.
  • •Signed Informed Consent from the Parent or legal guardian

排除标准

  • •Presence of a significant medical that in the opinion of the Investigator precludes participation in the study
  • •Known infection with human immunodeficiency virus (HIV)
  • •Presence in the serum of hepatitis A virus (HAV) or hepatitis C virus (HCV) antibody.
  • •History of congenital abdominal disorders, intussusception, abdominal surgery or any other congenital disorder.
  • •Participation in research involving another investigational product (defined as receipt of investigational product) 30 days before planned date of first vaccination or concurrently participating in another clinical study, at any time during the study period, in which the child has been or will be exposed to an investigational or a non-investigational product
  • •Clinically significant abnormalities on physical examination
  • •Clinically significant abnormalities in screening hematology, serum chemistry as determined by the PI or the PI in consultation with the Study Physician
  • •History of febrile illness within 48 hours prior to vaccination
  • •Known or suspected impairment of immunological function based on medical history and physical examination
  • •Prior receipt of any Shigella vaccine
  • •Fever at the time of immunization. Fever is defined as a temperature ≥ 37.5C (99.5F) on axillary, oral, or tympanic measurement
  • •History of known shigellosis, chronic diarrhea/dysentery in the past 2 months
  • •Current use of iron or zinc supplements within the past 7 days; current use of antacids (H2 blockers, omeprazol, OTC agents) or immunosuppressive drug
  • •Allergy to quinolone, sulfa, and penicillin classes of antibiotics
  • •Clinical evidence of active gastrointestinal illness
  • •Prior receipt of a blood transfusion or blood products, including immunoglobulins
  • •Presence of any significant systemic disorder (cardiovascular, pulmonary, hepatic, renal, gastrointestinal, endocrine, immunological, dermatological, neurological, cancer or autoimmune disease) as determined by medical history and/or physical examination which would endanger the participant's health or is likely to result in non-conformance to the protocol.
  • •History of any neurologic disorders or seizures.
  • •Acute disease at the time of enrolment
  • •Medically significant malnutrition, defined as moderate malnutrition (wt-for-age z-score between -3.0 and -2.0) and severe malnutrition (wt-for-age z-score <-3.0 or edema)
  • •Any conditions which, in the opinion of the investigator, might jeopardize the safety of study participants or interfere with the evaluation of the study objectives
  • •Receipt of antimicrobial drugs for any reason or a fever ≥ 38C within 7 days before vaccination
  • •History of diarrhea during the 7 days before vaccination.
  • •Has any household member(s) who is immunocompromised or under the age of 1 year old.
  • •Culture or polymerase chain reaction (PCR) positive for any Shigella strain

结局指标

主要结局

Maximum Severity of Reactogenicity by Vaccination

时间窗: 72 hours after each vaccination (Day 3, Day 31, Day 59)

All toddlers were monitored for evidence of immediate reactions, assessed for systemic reactogenicity (fever, irritability, decreased appetite, and decreased activity) and gastrointestinal (GI) symptoms (abdominal pain, nausea, vomiting, loose stool, diarrhea, dysentery, bloating, excess flatulence, constipation) during the 72 hours following each vaccine dose.

Number of Participants With Adverse Events Occurring Within 28 Days After Any Vaccination by Maximum Severity

时间窗: Up to 28 days after any vaccination (up to Day 84)

All toddlers were monitored for the occurrence of any adverse event (AE) or serious adverse event (SAE). Toddlers visited the clinic for safety assessments approximately one month after each vaccination. Grades are based on maximum severity per participant.

次要结局

  • Geometric Mean Fold Change From Baseline in Immunoglobulin A (IgA) Antibodies in Antibody Lymphocyte Supernatant (ALS): Invaplex Antigens(Baseline (Day 0, pre-vaccination) and Days 7, 35, and 63)
  • Geometric Mean Fold Change From Baseline in Immunoglobulin G (IgG) Antibodies in Antibody Lymphocyte Supernatant (ALS): Lipopolysaccharide (LPS)(Baseline (Day 0, pre-vaccination) and Days 7, 35, and 63)
  • Geometric Mean Fold Change From Baseline in Immunoglobulin M (IgM) Antibodies in Antibody Lymphocyte Supernatant (ALS): Lipopolysaccharide (LPS) Antigen(Baseline (Day 0, pre-vaccination) and Days 7, 35, and 63)
  • Count of Participants With 4-fold Rise From Baseline in Immunoglobulin A (IgA) Antibodies in Antibody Lymphocyte Supernatant (ALS): Invaplex Antigen(Days 7, 35, and 63)
  • Geometric Mean Titer (GMT) of Immunoglobulin A (IgA) Antibodies in Antibody Lymphocyte Supernatant (ALS): Invaplex Antigens(Days 0, 7, 35, and 63)
  • Geometric Mean Titer (GMT) of Immunoglobulin A (IgA) Antibodies in Lymphocyte Supernatant (ALS): Lipopolysaccharide (LPS) Antigen(Days 0, 7, 35, and 63)
  • Geometric Mean Fold Change From Baseline in Immunoglobulin G (IgG) Antibodies in Antibody Lymphocyte Supernatant (ALS): Invaplex Antigen(Baseline (Day 0, pre-vaccination) and Days 7, 35, and 63)
  • Geometric Mean Fold Change From Baseline in Immunoglobulin M (IgM) Antibodies in Antibody Lymphocyte Supernatant (ALS): Invaplex Antigen(Baseline (Day 0, pre-vaccination) and Days 7, 35, and 63)
  • Count of Participants With 4-fold Rise From Baseline in Immunoglobulin G (IgG) Antibodies in Antibody Lymphocyte Supernatant (ALS): Invaplex Antigen(Days 7, 35, and 63)
  • Geometric Mean Titer (GMT) of Immunoglobulin G (IgG) Antibodies in Antibody Lymphocyte Supernatant (ALS): Invaplex Antigen(Days 0, 7, 35, and 63)
  • Geometric Mean Titer (GMT) of Immunoglobulin G (IgG) Antibodies in Antibody Lymphocyte Supernatant (ALS): Lipopolysaccharide (LPS)(Days 0, 7, 35, and 63)
  • Geometric Mean Fold Change From Baseline in Immunoglobulin A (IgA) Antibodies in Antibody Lymphocyte Supernatant (ALS): Lipopolysaccharide (LPS) Antigen(Baseline (Day 0, pre-vaccination) and Days 7, 35, and 63)
  • Geometric Mean Titer (GMT) of Immunoglobulin A (IgA) Antibodies in Serum: Invaplex Antigens(Days 0, 7, 35, and 63)
  • Geometric Mean Fold Change From Baseline in Immunoglobulin A (IgA) Antibodies in Serum: Lipopolysaccharide (LPS) Antigen(Baseline (Day 0, pre-vaccination) and Days 7, 35, and 63)
  • Count of Participants With 4-fold Rise From Baseline in Immunoglobulin M (IgM) Antibodies in Antibody Lymphocyte Supernatant (ALS): Lipopolysaccharide (LPS) Antigen(Days 7, 35, and 63)
  • Geometric Mean Titer (GMT) of Immunoglobulin M (IgM) Antibodies in Antibody Lymphocyte Supernatant (ALS): Lipopolysaccharide (LPS) Antigen(Days 0, 7, 35, and 63)
  • Count of Participants With 4-fold Rise From Baseline in Immunoglobulin M (IgM) Antibodies in Antibody Lymphocyte Supernatant (ALS): Invaplex Antigen(Days 7, 35, and 63)
  • Count of Participants With 4-fold Rise From Baseline in Immunoglobulin A (IgA) Antibodies in Antibody Lymphocyte Supernatant (ALS): Lipopolysaccharide (LPS) Antigen(Days 7, 35, and 63)
  • Geometric Mean Titer (GMT) of Immunoglobulin A (IgA) Antibodies in Serum: Lipopolysaccharide (LPS) Antigen(Days 0, 7, 35, and 63)
  • Geometric Mean Titer (GMT) of Immunoglobulin M (IgM) Antibodies in Serum: Lipopolysaccharide (LPS) Antigen(Days 0, 7, 35, and 63)
  • Geometric Mean Titer (GMT) of Immunoglobulin M (IgM) Antibodies in Antibody Lymphocyte Supernatant (ALS): Invaplex Antigen(Days 0, 7, 35, and 63)
  • Geometric Mean Fold Change From Baseline in Immunoglobulin M (IgM) Antibodies in Serum : Invaplex Antigen(Baseline (Day 0, pre-vaccination) and Days 7, 35, and 63)
  • Geometric Mean Fold Change From Baseline in Immunoglobulin M (IgM) Antibodies in Serum: Lipopolysaccharide (LPS) Antigen(Baseline (Day 0, pre-vaccination) and Days 7, 35, and 63)
  • Count of Participants With 4-fold Rise in Immunoglobulin G (IgG) Antibodies in Serum From Baseline: Invaplex Antigen(Days 7, 35, and 63)
  • Geometric Mean Titer (GMT) of Immunoglobulin A (IgA) Antibodies in Stool: Lipopolysaccharide (LPS) Antigen(Days 0, 7, 28, 35, 56, 63, and 84)
  • Count of Participants With 4-fold Rise From Baseline in Immunoglobulin A (IgA) Antibodies in Stool: Lipopolysaccharide (LPS) Antigen(Days 7, 28, 35, 56, 63, and 84)
  • Count of Participants With 4-fold Rise From Baseline in Immunoglobulin G (IgG) Antibodies in Antibody Lymphocyte Supernatant (ALS): Lipopolysaccharide (LPS) Antigen(Days 7, 35, and 63)
  • Geometric Mean Titer (GMT) of Immunoglobulin G (IgG) Antibodies in Serum: Invaplex Antigen(Days 0, 7, 35, and 63)
  • Geometric Mean Titer (GMT) of Immunoglobulin M (IgM) Antibodies in Serum: Invaplex Antigen(Days 0, 7, 35, and 63)
  • Geometric Mean Fold Change From Baseline in Immunoglobulin A (IgA) Antibodies in Serum: Invaplex Antigens(Baseline (Day 0, pre-vaccination) and Days 7, 35, and 63)
  • Count of Participants With 4-fold Rise in Immunoglobulin G (IgG) Antibodies in Serum From Baseline: Lipopolysaccharide (LPS) Antigen(Days 7, 35, and 63)
  • Geometric Mean Titer (GMT) of Immunoglobulin G (IgG) Antibodies in Serum: Lipopolysaccharide (LPS)(Days 0, 7, 35, and 63)
  • Count of Participants With 4-fold Rise in Immunoglobulin A (IgA) Antibodies in Serum From Baseline: Invaplex Antigen(Days 7, 35, and 63)
  • Count of Participants With 4-fold Rise in Immunoglobulin A (IgA) Antibodies in Serum From Baseline: Lipopolysaccharide (LPS) Antigen(Days 7, 35, and 63)
  • Count of Participants With 4-fold Rise in Immunoglobulin M (IgM) Antibodies in Serum From Baseline: Lipopolysaccharide (LPS) Antigen(Days 7, 35, and 63)
  • Geometric Mean Titer (GMT) of Immunoglobulin A (IgA) Antibodies in Stool: Invaplex Antigen(Days 0, 7, 28, 35, 56, 63, and 84)
  • Geometric Mean Fold Change From Baseline in Immunoglobulin G (IgG) Antibodies in Serum: Invaplex Antigen(Baseline (Day 0, pre-vaccination) and Days 7, 35, and 63)
  • Geometric Mean Fold Change From Baseline in Immunoglobulin G (IgG) Antibodies in Serum: Lipopolysaccharide (LPS)(Baseline (Day 0, pre-vaccination) and Days 7, 35, and 63)
  • Count of Participants With 4-fold Rise in Immunoglobulin M (IgM) Antibodies in Serum From Baseline: Invaplex Antigen(Days 7, 35, and 63)
  • Geometric Mean Fold Change From Baseline in Immunoglobulin A (IgA) Antibodies in Stool: Invaplex Antigens(Baseline (Day 0, pre-vaccination) and Days 7, 28, 35, 56, 63, and 84)
  • Geometric Mean Fold Change From Baseline in Immunoglobulin A (IgA) Antibodies in Stool: Lipopolysaccharide (LPS) Antigen(Baseline (Day 0, pre-vaccination) and Days 7, 28, 35, 56, 63, and 84)
  • Count of Participants With 4-fold Rise From Baseline in Immunoglobulin A (IgA) Antibodies in Stool: Invaplex Antigen(Days 7, 28, 35, 56, 63, and 84)

研究者

发起方
PATH
申办方类型
Other
责任方
Sponsor

研究点 (1)

Loading locations...

相似试验

已完成
1 期
Effect of Adjuvant & Route of Administration on Safety & Immunogenicity of NDV-3 VaccineStaphylococcal InfectionsYeast InfectionsCandidiasis
NCT01447407NovaDigm Therapeutics, Inc.164
已完成
1 期
Study of the Safety and Immunogenicity of an Intranasal Vaccine for Respiratory Syncytial Virus in Seropositive ChildrenRespiratory Syncytial Virus Infections
NCT04444284Meissa Vaccines, Inc.34
Unknown
1 期
Safety and Immunogenicity of an Intranasal Vaccine for Respiratory Syncytial Virus in Seronegative Children 6-36 MonthsRespiratory Syncytial Virus (RSV)
NCT04909021Meissa Vaccines, Inc.63
已完成
1 期
Chiron Corp HCV E1/E2 VaccineHepatitis C
NCT00500747National Institute of Allergy and Infectious Diseases (NIAID)60
已完成
1 期
Safety Study of Hepatitis E Vaccine (HEV239)Hepatitis EImmunisation
NCT03827395National Institute of Allergy and Infectious Diseases (NIAID)25