Clinical trial NCT02934178: Shigella WRSS1 Vaccine Trial in Bangladesh
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Diarrhea
Keywords: shigellosis
Enterobacteriaceae Infections
Gram-Negative Bacterial Infections
Bacterial Infections
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Intestinal Diseases
Lead sponsor: PATH
Sponsor class: OTHER
Collaborators: name: International Centre for Diarrhoeal Disease Research, Bangladesh
First posted: 2016-10-14
Enrollment: 16
Sex: ALL
Minimum age (years): 12
Maximum age (years): 24
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

1. Presence of a significant medical that in the opinion of the Investigator precludes participation in the study
2. Known infection with human immunodeficiency virus (HIV)
3. Presence in the serum of hepatitis A virus (HAV) or hepatitis C virus (HCV) antibody.
4. History of congenital abdominal disorders, intussusception, abdominal surgery or any other congenital disorder.
5. 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
6. Clinically significant abnormalities on physical examination
7. Clinically significant abnormalities in screening hematology, serum chemistry as determined by the PI or the PI in consultation with the Study Physician
8. History of febrile illness within 48 hours prior to vaccination
9. Known or suspected impairment of immunological function based on medical history and physical examination
10. Prior receipt of any Shigella vaccine
11. Fever at the time of immunization. Fever is defined as a temperature ≥ 37.5C (99.5F) on axillary, oral, or tympanic measurement
12. History of known shigellosis, chronic diarrhea/dysentery in the past 2 months
13. Current use of iron or zinc supplements within the past 7 days; current use of antacids (H2 blockers, omeprazol, OTC agents) or immunosuppressive drug
14. Allergy to quinolone, sulfa, and penicillin classes of antibiotics
15. Clinical evidence of active gastrointestinal illness
16. Prior receipt of a blood transfusion or blood products, including immunoglobulins
17. 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.
18. History of any neurologic disorders or seizures.
19. Acute disease at the time of enrolment
20. 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)
21. 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
22. Receipt of antimicrobial drugs for any reason or a fever ≥ 38C within 7 days before vaccination
23. History of diarrhea during the 7 days before vaccination.
24. Has any household member(s) who is immunocompromised or under the age of 1 year old.
25. Culture or polymerase chain reaction (PCR) positive for any Shigella strain

Primary outcomes:
measure: Maximum Severity of Reactogenicity by Vaccination
timeFrame: 72 hours after each vaccination (Day 3, Day 31, Day 59)
measure: Number of Participants With Adverse Events Occurring Within 28 Days After Any Vaccination by Maximum Severity
timeFrame: Up to 28 days after any vaccination (up to Day 84)
Secondary outcomes:
measure: Geometric Mean Titer (GMT) of Immunoglobulin A (IgA) Antibodies in Antibody Lymphocyte Supernatant (ALS): Invaplex Antigens
timeFrame: Days 0, 7, 35, and 63
measure: Geometric Mean Titer (GMT) of Immunoglobulin A (IgA) Antibodies in Lymphocyte Supernatant (ALS): Lipopolysaccharide (LPS) Antigen
timeFrame: Days 0, 7, 35, and 63
measure: Geometric Mean Titer (GMT) of Immunoglobulin G (IgG) Antibodies in Antibody Lymphocyte Supernatant (ALS): Invaplex Antigen
timeFrame: Days 0, 7, 35, and 63
measure: Geometric Mean Titer (GMT) of Immunoglobulin G (IgG) Antibodies in Antibody Lymphocyte Supernatant (ALS): Lipopolysaccharide (LPS)
timeFrame: Days 0, 7, 35, and 63
measure: Geometric Mean Titer (GMT) of Immunoglobulin M (IgM) Antibodies in Antibody Lymphocyte Supernatant (ALS): Invaplex Antigen
timeFrame: Days 0, 7, 35, and 63
measure: Geometric Mean Titer (GMT) of Immunoglobulin M (IgM) Antibodies in Antibody Lymphocyte Supernatant (ALS): Lipopolysaccharide (LPS) Antigen
timeFrame: Days 0, 7, 35, and 63
measure: Geometric Mean Fold Change From Baseline in Immunoglobulin A (IgA) Antibodies in Antibody Lymphocyte Supernatant (ALS): Invaplex Antigens
timeFrame: Baseline (Day 0, pre-vaccination) and Days 7, 35, and 63
measure: Geometric Mean Fold Change From Baseline in Immunoglobulin A (IgA) Antibodies in Antibody Lymphocyte Supernatant (ALS): Lipopolysaccharide (LPS) Antigen
timeFrame: Baseline (Day 0, pre-vaccination) and Days 7, 35, and 63
measure: Geometric Mean Fold Change From Baseline in Immunoglobulin G (IgG) Antibodies in Antibody Lymphocyte Supernatant (ALS): Invaplex Antigen
timeFrame: Baseline (Day 0, pre-vaccination) and Days 7, 35, and 63
measure: Geometric Mean Fold Change From Baseline in Immunoglobulin G (IgG) Antibodies in Antibody Lymphocyte Supernatant (ALS): Lipopolysaccharide (LPS)
timeFrame: Baseline (Day 0, pre-vaccination) and Days 7, 35, and 63
measure: Geometric Mean Fold Change From Baseline in Immunoglobulin M (IgM) Antibodies in Antibody Lymphocyte Supernatant (ALS): Invaplex Antigen
timeFrame: Baseline (Day 0, pre-vaccination) and Days 7, 35, and 63
measure: Geometric Mean Fold Change From Baseline in Immunoglobulin M (IgM) Antibodies in Antibody Lymphocyte Supernatant (ALS): Lipopolysaccharide (LPS) Antigen
timeFrame: Baseline (Day 0, pre-vaccination) and Days 7, 35, and 63
measure: Count of Participants With 4-fold Rise From Baseline in Immunoglobulin A (IgA) Antibodies in Antibody Lymphocyte Supernatant (ALS): Invaplex Antigen
timeFrame: Days 7, 35, and 63
measure: Count of Participants With 4-fold Rise From Baseline in Immunoglobulin G (IgG) Antibodies in Antibody Lymphocyte Supernatant (ALS): Invaplex Antigen
timeFrame: Days 7, 35, and 63
measure: Count of Participants With 4-fold Rise From Baseline in Immunoglobulin M (IgM) Antibodies in Antibody Lymphocyte Supernatant (ALS): Invaplex Antigen
timeFrame: Days 7, 35, and 63
measure: Count of Participants With 4-fold Rise From Baseline in Immunoglobulin A (IgA) Antibodies in Antibody Lymphocyte Supernatant (ALS): Lipopolysaccharide (LPS) Antigen
timeFrame: Days 7, 35, and 63
measure: Count of Participants With 4-fold Rise From Baseline in Immunoglobulin G (IgG) Antibodies in Antibody Lymphocyte Supernatant (ALS): Lipopolysaccharide (LPS) Antigen
timeFrame: Days 7, 35, and 63
measure: Count of Participants With 4-fold Rise From Baseline in Immunoglobulin M (IgM) Antibodies in Antibody Lymphocyte Supernatant (ALS): Lipopolysaccharide (LPS) Antigen
timeFrame: Days 7, 35, and 63
measure: Geometric Mean Titer (GMT) of Immunoglobulin A (IgA) Antibodies in Serum: Invaplex Antigens
timeFrame: Days 0, 7, 35, and 63
measure: Geometric Mean Titer (GMT) of Immunoglobulin A (IgA) Antibodies in Serum: Lipopolysaccharide (LPS) Antigen
timeFrame: Days 0, 7, 35, and 63
measure: Geometric Mean Titer (GMT) of Immunoglobulin G (IgG) Antibodies in Serum: Invaplex Antigen
timeFrame: Days 0, 7, 35, and 63
measure: Geometric Mean Titer (GMT) of Immunoglobulin G (IgG) Antibodies in Serum: Lipopolysaccharide (LPS)
timeFrame: Days 0, 7, 35, and 63
measure: Geometric Mean Titer (GMT) of Immunoglobulin M (IgM) Antibodies in Serum: Invaplex Antigen
timeFrame: Days 0, 7, 35, and 63
measure: Geometric Mean Titer (GMT) of Immunoglobulin M (IgM) Antibodies in Serum: Lipopolysaccharide (LPS) Antigen
timeFrame: Days 0, 7, 35, and 63
measure: Geometric Mean Fold Change From Baseline in Immunoglobulin A (IgA) Antibodies in Serum: Invaplex Antigens
timeFrame: Baseline (Day 0, pre-vaccination) and Days 7, 35, and 63
measure: Geometric Mean Fold Change From Baseline in Immunoglobulin A (IgA) Antibodies in Serum: Lipopolysaccharide (LPS) Antigen
timeFrame: Baseline (Day 0, pre-vaccination) and Days 7, 35, and 63
measure: Geometric Mean Fold Change From Baseline in Immunoglobulin G (IgG) Antibodies in Serum: Invaplex Antigen
timeFrame: Baseline (Day 0, pre-vaccination) and Days 7, 35, and 63
measure: Geometric Mean Fold Change From Baseline in Immunoglobulin G (IgG) Antibodies in Serum: Lipopolysaccharide (LPS)
timeFrame: Baseline (Day 0, pre-vaccination) and Days 7, 35, and 63
measure: Geometric Mean Fold Change From Baseline in Immunoglobulin M (IgM) Antibodies in Serum : Invaplex Antigen
timeFrame: Baseline (Day 0, pre-vaccination) and Days 7, 35, and 63
measure: Geometric Mean Fold Change From Baseline in Immunoglobulin M (IgM) Antibodies in Serum: Lipopolysaccharide (LPS) Antigen
timeFrame: Baseline (Day 0, pre-vaccination) and Days 7, 35, and 63
measure: Count of Participants With 4-fold Rise in Immunoglobulin A (IgA) Antibodies in Serum From Baseline: Invaplex Antigen
timeFrame: Days 7, 35, and 63
measure: Count of Participants With 4-fold Rise in Immunoglobulin G (IgG) Antibodies in Serum From Baseline: Invaplex Antigen
timeFrame: Days 7, 35, and 63
measure: Count of Participants With 4-fold Rise in Immunoglobulin M (IgM) Antibodies in Serum From Baseline: Invaplex Antigen
timeFrame: Days 7, 35, and 63
measure: Count of Participants With 4-fold Rise in Immunoglobulin A (IgA) Antibodies in Serum From Baseline: Lipopolysaccharide (LPS) Antigen
timeFrame: Days 7, 35, and 63
measure: Count of Participants With 4-fold Rise in Immunoglobulin G (IgG) Antibodies in Serum From Baseline: Lipopolysaccharide (LPS) Antigen
timeFrame: Days 7, 35, and 63
measure: Count of Participants With 4-fold Rise in Immunoglobulin M (IgM) Antibodies in Serum From Baseline: Lipopolysaccharide (LPS) Antigen
timeFrame: Days 7, 35, and 63
measure: Geometric Mean Titer (GMT) of Immunoglobulin A (IgA) Antibodies in Stool: Invaplex Antigen
timeFrame: Days 0, 7, 28, 35, 56, 63, and 84
measure: Geometric Mean Titer (GMT) of Immunoglobulin A (IgA) Antibodies in Stool: Lipopolysaccharide (LPS) Antigen
timeFrame: Days 0, 7, 28, 35, 56, 63, and 84
measure: Geometric Mean Fold Change From Baseline in Immunoglobulin A (IgA) Antibodies in Stool: Invaplex Antigens
timeFrame: Baseline (Day 0, pre-vaccination) and Days 7, 28, 35, 56, 63, and 84
measure: Geometric Mean Fold Change From Baseline in Immunoglobulin A (IgA) Antibodies in Stool: Lipopolysaccharide (LPS) Antigen
timeFrame: Baseline (Day 0, pre-vaccination) and Days 7, 28, 35, 56, 63, and 84
measure: Count of Participants With 4-fold Rise From Baseline in Immunoglobulin A (IgA) Antibodies in Stool: Invaplex Antigen
timeFrame: Days 7, 28, 35, 56, 63, and 84
measure: Count of Participants With 4-fold Rise From Baseline in Immunoglobulin A (IgA) Antibodies in Stool: Lipopolysaccharide (LPS) Antigen
timeFrame: Days 7, 28, 35, 56, 63, and 84
Other outcomes:
Locations:
city: Mirpur
country: Bangladesh
facility: Mirpur Field Office
Study officials:
affiliation: International Centre for Diarrhoeal Disease Research, Bangladesh
name: Rubhana Raqib, MD
role: PRINCIPAL_INVESTIGATOR
References: