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NCT Number: NCT02934178

Shigella WRSS1 Vaccine Trial in Bangladesh

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.

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Key information

Conditions

Diarrhea Bacterial Infections Bacterial Infections and Mycoses Digestive System Diseases Dysentery Dysentery, Bacillary Enterobacteriaceae Infections Gastroenteritis Gastrointestinal Diseases Gram-Negative Bacterial Infections Infections Intestinal Diseases Pathological Conditions, Signs and Symptoms Signs and Symptoms Signs and Symptoms, Digestive

Age range

12 month–24 month

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Mirpur Field Office

Mirpur, Bangladesh

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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

Exclusion criteria

  • 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

Treatment and study plan

Shigella sonnei Strain WRSS1 Vaccine

Biological

Live attenuated, oral Shigella WRSS1 vaccine

Placebo

Biological

Sterile saline solution

Primary outcomes

  1. Maximum Severity of Reactogenicity by Vaccination

    Time frame: 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.

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

    Time frame: 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.

Secondary outcomes

  1. Geometric Mean Titer (GMT) of Immunoglobulin A (IgA) Antibodies in Antibody Lymphocyte Supernatant (ALS): Invaplex Antigens

    Time frame: Days 0, 7, 35, and 63

    The mucosal immune response to WRSS1 was evaluated by assessing specific IgA antibody responses to S. sonnei Invaplex using the 'antibodies in lymphocyte supernatant' (ALS) assay on culture supernatants of cultured peripheral blood mononuclear cells from different study days (Days 0, 7, 35, and 63) to determine Invaplex-specific IgA response from circulating lymphocytes. Invaplex is a mixture of purified S. sonnei lipopolysaccharide (LPS) and purified protein antigens IpaB and IpaC.

  2. Geometric Mean Titer (GMT) of Immunoglobulin A (IgA) Antibodies in Lymphocyte Supernatant (ALS): Lipopolysaccharide (LPS) Antigen

    Time frame: Days 0, 7, 35, and 63

    The mucosal immune response to WRSS1 was evaluated by assessing specific IgA antibody responses to S. sonnei lipopolysaccharide (LPS) using the 'antibodies in lymphocyte supernatant' (ALS) assay on culture supernatants from cultured peripheral blood mononuclear cells from different study days (Days 0, 7, 35, and 63) to determine LPS-specific IgA response from circulating lymphocytes.

  3. Geometric Mean Titer (GMT) of Immunoglobulin G (IgG) Antibodies in Antibody Lymphocyte Supernatant (ALS): Invaplex Antigen

    Time frame: Days 0, 7, 35, and 63

    The mucosal immune response to WRSS1 was evaluated by assessing specific IgG antibody responses to S. sonnei Invaplex using the 'antibodies in lymphocyte supernatant' (ALS) assay on culture supernatants of cultured peripheral blood mononuclear cells from different study days (Days 0, 7, 35, and 63) to determine Invaplex-specific IgG response from circulating lymphocytes. Invaplex is a mixture of purified S. sonnei lipopolysaccharide (LPS) and purified protein antigens IpaB and IpaC.

  4. Geometric Mean Titer (GMT) of Immunoglobulin G (IgG) Antibodies in Antibody Lymphocyte Supernatant (ALS): Lipopolysaccharide (LPS)

    Time frame: Days 0, 7, 35, and 63

    The mucosal immune response to WRSS1 was evaluated by assessing specific IgG antibody responses to S. sonnei LPS using the 'antibodies in lymphocyte supernatant' (ALS) assay on culture supernatants of cultured peripheral blood mononuclear cells from different study days (Days 0, 7, 35, and 63) to determine LPS-specific IgG response from circulating lymphocytes.

  5. Geometric Mean Titer (GMT) of Immunoglobulin M (IgM) Antibodies in Antibody Lymphocyte Supernatant (ALS): Invaplex Antigen

    Time frame: Days 0, 7, 35, and 63

    The mucosal immune response to WRSS1 was evaluated by assessing specific IgM antibody responses to S. sonnei Invaplex using the 'antibodies in lymphocyte supernatant' (ALS) assay on culture supernatants of cultured peripheral blood mononuclear cells from different study days (Days 0, 7, 35, and 63) to determine Invaplex-specific IgM response from circulating lymphocytes. Invaplex is a mixture of purified S. sonnei lipopolysaccharide (LPS) and purified protein antigens IpaB and IpaC.

  6. Geometric Mean Titer (GMT) of Immunoglobulin M (IgM) Antibodies in Antibody Lymphocyte Supernatant (ALS): Lipopolysaccharide (LPS) Antigen

    Time frame: Days 0, 7, 35, and 63

    The mucosal immune response to WRSS1 was evaluated by assessing specific IgM antibody responses to S. sonnei LPS using the 'antibodies in lymphocyte supernatant' (ALS) assay on culture supernatants of cultured peripheral blood mononuclear cells from different study days (Days 0, 7, 35, and 63) to determine LPS-specific IgM response from circulating lymphocytes.

  7. Geometric Mean Fold Change From Baseline in Immunoglobulin A (IgA) Antibodies in Antibody Lymphocyte Supernatant (ALS): Invaplex Antigens

    Time frame: Baseline (Day 0, pre-vaccination) and Days 7, 35, and 63

  8. Geometric Mean Fold Change From Baseline in Immunoglobulin A (IgA) Antibodies in Antibody Lymphocyte Supernatant (ALS): Lipopolysaccharide (LPS) Antigen

    Time frame: Baseline (Day 0, pre-vaccination) and Days 7, 35, and 63

  9. Geometric Mean Fold Change From Baseline in Immunoglobulin G (IgG) Antibodies in Antibody Lymphocyte Supernatant (ALS): Invaplex Antigen

    Time frame: Baseline (Day 0, pre-vaccination) and Days 7, 35, and 63

  10. Geometric Mean Fold Change From Baseline in Immunoglobulin G (IgG) Antibodies in Antibody Lymphocyte Supernatant (ALS): Lipopolysaccharide (LPS)

    Time frame: Baseline (Day 0, pre-vaccination) and Days 7, 35, and 63

  11. Geometric Mean Fold Change From Baseline in Immunoglobulin M (IgM) Antibodies in Antibody Lymphocyte Supernatant (ALS): Invaplex Antigen

    Time frame: Baseline (Day 0, pre-vaccination) and Days 7, 35, and 63

  12. Geometric Mean Fold Change From Baseline in Immunoglobulin M (IgM) Antibodies in Antibody Lymphocyte Supernatant (ALS): Lipopolysaccharide (LPS) Antigen

    Time frame: Baseline (Day 0, pre-vaccination) and Days 7, 35, and 63

  13. Count of Participants With 4-fold Rise From Baseline in Immunoglobulin A (IgA) Antibodies in Antibody Lymphocyte Supernatant (ALS): Invaplex Antigen

    Time frame: Days 7, 35, and 63

  14. Count of Participants With 4-fold Rise From Baseline in Immunoglobulin G (IgG) Antibodies in Antibody Lymphocyte Supernatant (ALS): Invaplex Antigen

    Time frame: Days 7, 35, and 63

  15. Count of Participants With 4-fold Rise From Baseline in Immunoglobulin M (IgM) Antibodies in Antibody Lymphocyte Supernatant (ALS): Invaplex Antigen

    Time frame: Days 7, 35, and 63

  16. Count of Participants With 4-fold Rise From Baseline in Immunoglobulin A (IgA) Antibodies in Antibody Lymphocyte Supernatant (ALS): Lipopolysaccharide (LPS) Antigen

    Time frame: Days 7, 35, and 63

  17. Count of Participants With 4-fold Rise From Baseline in Immunoglobulin G (IgG) Antibodies in Antibody Lymphocyte Supernatant (ALS): Lipopolysaccharide (LPS) Antigen

    Time frame: Days 7, 35, and 63

  18. Count of Participants With 4-fold Rise From Baseline in Immunoglobulin M (IgM) Antibodies in Antibody Lymphocyte Supernatant (ALS): Lipopolysaccharide (LPS) Antigen

    Time frame: Days 7, 35, and 63

  19. Geometric Mean Titer (GMT) of Immunoglobulin A (IgA) Antibodies in Serum: Invaplex Antigens

    Time frame: Days 0, 7, 35, and 63

    The systemic immune response to WRSS1 was evaluated by assessing the IgA antibody response to S. sonnei Invaplex in serum/plasma samples at Days 0, 7, 35 and 63. Invaplex is a mixture of purified S. sonnei LPS and purified protein antigens IpaB and IpaC. Serotype-specific LPS from the Walter Reed Army Institute was used to coat the enzyme-linked immunosorbent assay (ELISA) plates.

  20. Geometric Mean Titer (GMT) of Immunoglobulin A (IgA) Antibodies in Serum: Lipopolysaccharide (LPS) Antigen

    Time frame: Days 0, 7, 35, and 63

    The systemic immune response to WRSS1 was evaluated by assessing the IgA antibody response to S. sonnei 2a LPS in serum/plasma samples at Days 0, 7, 35 and 63. Serotype-specific lipopolysaccharide (LPS) from the Walter Reed Army Institute was used to coat the ELISA plates.

  21. Geometric Mean Titer (GMT) of Immunoglobulin G (IgG) Antibodies in Serum: Invaplex Antigen

    Time frame: Days 0, 7, 35, and 63

    The systemic immune response to WRSS1 was evaluated by assessing the IgG antibody response to S. sonnei Invaplex in serum/plasma samples at Days 0, 7, 35 and 63. Invaplex is a mixture of purified S. sonnei LPS and purified protein antigens IpaB and IpaC. Serotype-specific LPS from the Walter Reed Army Institute was used to coat the ELISA plates.

  22. Geometric Mean Titer (GMT) of Immunoglobulin G (IgG) Antibodies in Serum: Lipopolysaccharide (LPS)

    Time frame: Days 0, 7, 35, and 63

    The systemic immune response to WRSS1 was evaluated by assessing the IgG antibody response to S. sonnei 2a LPS in serum/plasma samples at Days 0, 7, 35 and 63. Serotype-specific LPS from the Walter Reed Army Institute was used to coat the ELISA plates.

  23. Geometric Mean Titer (GMT) of Immunoglobulin M (IgM) Antibodies in Serum: Invaplex Antigen

    Time frame: Days 0, 7, 35, and 63

    The systemic immune response to WRSS1 was evaluated by assessing the IgM antibody response to S. sonnei Invaplex in serum/plasma samples at Days 0, 7, 35 and 63. Invaplex is a mixture of purified S. sonnei LPS and purified protein antigens IpaB and IpaC. Serotype-specific LPS from the Walter Reed Army Institute was used to coat the ELISA plates.

  24. Geometric Mean Titer (GMT) of Immunoglobulin M (IgM) Antibodies in Serum: Lipopolysaccharide (LPS) Antigen

    Time frame: Days 0, 7, 35, and 63

    The systemic immune response to WRSS1 was evaluated by assessing the IgM antibody response to S. sonnei 2a LPS in serum/plasma samples at Days 0, 7, 35 and 63. Serotype-specific LPS from the Walter Reed Army Institute was used to coat the ELISA plates.

  25. Geometric Mean Fold Change From Baseline in Immunoglobulin A (IgA) Antibodies in Serum: Invaplex Antigens

    Time frame: Baseline (Day 0, pre-vaccination) and Days 7, 35, and 63

  26. Geometric Mean Fold Change From Baseline in Immunoglobulin A (IgA) Antibodies in Serum: Lipopolysaccharide (LPS) Antigen

    Time frame: Baseline (Day 0, pre-vaccination) and Days 7, 35, and 63

  27. Geometric Mean Fold Change From Baseline in Immunoglobulin G (IgG) Antibodies in Serum: Invaplex Antigen

    Time frame: Baseline (Day 0, pre-vaccination) and Days 7, 35, and 63

  28. Geometric Mean Fold Change From Baseline in Immunoglobulin G (IgG) Antibodies in Serum: Lipopolysaccharide (LPS)

    Time frame: Baseline (Day 0, pre-vaccination) and Days 7, 35, and 63

  29. Geometric Mean Fold Change From Baseline in Immunoglobulin M (IgM) Antibodies in Serum : Invaplex Antigen

    Time frame: Baseline (Day 0, pre-vaccination) and Days 7, 35, and 63

  30. Geometric Mean Fold Change From Baseline in Immunoglobulin M (IgM) Antibodies in Serum: Lipopolysaccharide (LPS) Antigen

    Time frame: Baseline (Day 0, pre-vaccination) and Days 7, 35, and 63

  31. Count of Participants With 4-fold Rise in Immunoglobulin A (IgA) Antibodies in Serum From Baseline: Invaplex Antigen

    Time frame: Days 7, 35, and 63

  32. Count of Participants With 4-fold Rise in Immunoglobulin G (IgG) Antibodies in Serum From Baseline: Invaplex Antigen

    Time frame: Days 7, 35, and 63

  33. Count of Participants With 4-fold Rise in Immunoglobulin M (IgM) Antibodies in Serum From Baseline: Invaplex Antigen

    Time frame: Days 7, 35, and 63

  34. Count of Participants With 4-fold Rise in Immunoglobulin A (IgA) Antibodies in Serum From Baseline: Lipopolysaccharide (LPS) Antigen

    Time frame: Days 7, 35, and 63

  35. Count of Participants With 4-fold Rise in Immunoglobulin G (IgG) Antibodies in Serum From Baseline: Lipopolysaccharide (LPS) Antigen

    Time frame: Days 7, 35, and 63

  36. Count of Participants With 4-fold Rise in Immunoglobulin M (IgM) Antibodies in Serum From Baseline: Lipopolysaccharide (LPS) Antigen

    Time frame: Days 7, 35, and 63

  37. Geometric Mean Titer (GMT) of Immunoglobulin A (IgA) Antibodies in Stool: Invaplex Antigen

    Time frame: Days 0, 7, 28, 35, 56, 63, and 84

    The mucosal immune response to the WRSS1 was evaluated by assessing fecal IgA antibody responses to S. sonnei Invaplex in ELISA assays at Days 0, 7, 28, 35, 56, 63, and 84. Invaplex is a mixture of purified S. sonnei LPS and purified protein antigens IpaB and IpaC.

  38. Geometric Mean Titer (GMT) of Immunoglobulin A (IgA) Antibodies in Stool: Lipopolysaccharide (LPS) Antigen

    Time frame: Days 0, 7, 28, 35, 56, 63, and 84

    The mucosal immune response to the WRSS1 was evaluated by assessing fecal IgA antibody responses to S. sonnei LPS in ELISA assays at Days 0, 7, 28, 35, 56, 63, and 84.

  39. Geometric Mean Fold Change From Baseline in Immunoglobulin A (IgA) Antibodies in Stool: Invaplex Antigens

    Time frame: Baseline (Day 0, pre-vaccination) and Days 7, 28, 35, 56, 63, and 84

  40. Geometric Mean Fold Change From Baseline in Immunoglobulin A (IgA) Antibodies in Stool: Lipopolysaccharide (LPS) Antigen

    Time frame: Baseline (Day 0, pre-vaccination) and Days 7, 28, 35, 56, 63, and 84

  41. Count of Participants With 4-fold Rise From Baseline in Immunoglobulin A (IgA) Antibodies in Stool: Invaplex Antigen

    Time frame: Days 7, 28, 35, 56, 63, and 84

  42. Count of Participants With 4-fold Rise From Baseline in Immunoglobulin A (IgA) Antibodies in Stool: Lipopolysaccharide (LPS) Antigen

    Time frame: Days 7, 28, 35, 56, 63, and 84

Sponsors and collaborators

Lead sponsor

PATH

Other

Collaborators

  • International Centre for Diarrhoeal Disease Research, Bangladesh

Registry information

Official study 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)

Important dates

Study start
2017
Primary completion
2018
Study completion
2018
First posted
Oct 14, 2016
Registry last updated
Mar 31, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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