DiarrheaPhase 1NCT02934178
Shigella WRSS1 Vaccine Trial in Bangladesh
A Phase 1 study testing Shigella sonnei Strain WRSS1 Vaccine in people with Diarrhea, run by PATH at 1 site in Bangladesh.
Trial 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. Read more about this study
- Who is it for?
- Ages 12 to 24 monthsHealthy volunteers can take part
- Conditions the study is for
- Diarrhea
- What is being tested?
- Shigella sonnei Strain WRSS1 Vaccine
- Type of treatment
- Vaccines, Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 16 participants
- Where
- 1 siteBangladesh
- Study dates
- 23 Feb 2017to 10 Jan 2018
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 to 24 months
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
About this study
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)
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.
Read the 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.
- Conditions
- Diarrhea
- Being tested
- Shigella sonnei Strain WRSS1 Vaccine, Placebo
- Keywords
- shigellosis, Enterobacteriaceae Infections, Gram-Negative Bacterial Infections, Bacterial Infections, Gastroenteritis, Gastrointestinal Diseases, Digestive System Diseases, Intestinal Diseases
- Medical subject headings
- Diarrhea, Dysentery, Bacillary, Enterobacteriaceae Infections, Gram-Negative Bacterial Infections, Bacterial Infections, Gastroenteritis, Gastrointestinal Diseases, Digestive System Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Shigella sonnei Strain WRSS1 VaccineBiological
Live attenuated, oral Shigella WRSS1 vaccine
PlaceboBiological
Sterile saline solution
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1: WRSS1 3 x 10³ CFU | Experimental | Healthy toddlers receiving 3 oral doses of 3 x 10³ colony-forming units (CFU) of Shigella sonnei Strain WRSS1 approximately 4 weeks apart. Receives: Biological: Shigella sonnei Strain WRSS1 Vaccine |
| Cohort 2: WRSS1 3 x 10⁴ CFU | Experimental | Healthy toddlers receiving 3 oral doses of 3 x 10⁴ CFU of Shigella sonnei Strain WRSS1 approximately 4 weeks apart. Receives: Biological: Shigella sonnei Strain WRSS1 Vaccine |
| Cohort 3: WRSS1 3 x 10⁵ CFU | Experimental | Healthy toddlers receiving 3 oral doses of 3 x 10⁵ CFU of Shigella sonnei Strain WRSS1 approximately 4 weeks apart. Receives: Biological: Shigella sonnei Strain WRSS1 Vaccine |
| Cohort 4: WRSS1 3 x 10⁶ CFU | Experimental | Healthy toddlers receiving 3 oral doses of 3 x 10⁶ CFU of Shigella sonnei Strain WRSS1 approximately 4 weeks apart. Receives: Biological: Shigella sonnei Strain WRSS1 Vaccine |
| Cohort 1: Placebo | Placebo comparator | Healthy toddlers receiving 3 oral doses of placebo to match 3 x 10³ WRSS1 approximately 4 weeks apart. Receives: Biological: Placebo |
| Cohort 2: Placebo | Placebo comparator | Healthy toddlers receiving 3 oral doses of placebo to match 3 x 10⁴ WRSS1 approximately 4 weeks apart. Receives: Biological: Placebo |
| Cohort 3: Placebo | Placebo comparator | Healthy toddlers receiving 3 oral doses of placebo to match 3 x 10⁵ WRSS1 approximately 4 weeks apart. Receives: Biological: Placebo |
| Cohort 4: Placebo | Placebo comparator | Healthy toddlers receiving 3 oral doses of placebo to match 3 x 10⁶ WRSS1 approximately 4 weeks apart. Receives: Biological: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Severity of Reactogenicity by Vaccination
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.
Measured: 72 hours after each vaccination (Day 3, Day 31, Day 59)
Number of Participants With Adverse Events Occurring Within 28 Days After Any Vaccination by Maximum Severity
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.
Measured: Up to 28 days after any vaccination (up to Day 84)
Secondary outcomes (42)
Geometric Mean Titer (GMT) of Immunoglobulin A (IgA) Antibodies in Antibody Lymphocyte Supernatant (ALS): Invaplex Antigens
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.
Measured: Days 0, 7, 35, and 63
Geometric Mean Titer (GMT) of Immunoglobulin A (IgA) Antibodies in Lymphocyte Supernatant (ALS): Lipopolysaccharide (LPS) Antigen
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.
Measured: Days 0, 7, 35, and 63
Geometric Mean Titer (GMT) of Immunoglobulin G (IgG) Antibodies in Antibody Lymphocyte Supernatant (ALS): Invaplex Antigen
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.
Measured: Days 0, 7, 35, and 63
Geometric Mean Titer (GMT) of Immunoglobulin G (IgG) Antibodies in Antibody Lymphocyte Supernatant (ALS): Lipopolysaccharide (LPS)
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.
Measured: Days 0, 7, 35, and 63
Geometric Mean Titer (GMT) of Immunoglobulin M (IgM) Antibodies in Antibody Lymphocyte Supernatant (ALS): Invaplex Antigen
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.
Measured: Days 0, 7, 35, and 63
Geometric Mean Titer (GMT) of Immunoglobulin M (IgM) Antibodies in Antibody Lymphocyte Supernatant (ALS): Lipopolysaccharide (LPS) Antigen
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.
Measured: Days 0, 7, 35, and 63
Geometric Mean Fold Change From Baseline in Immunoglobulin A (IgA) Antibodies in Antibody Lymphocyte Supernatant (ALS): Invaplex Antigens
Measured: Baseline (Day 0, pre-vaccination) and Days 7, 35, and 63
Geometric Mean Fold Change From Baseline in Immunoglobulin A (IgA) Antibodies in Antibody Lymphocyte Supernatant (ALS): Lipopolysaccharide (LPS) Antigen
Measured: 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): Invaplex Antigen
Measured: 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)
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: Days 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
Measured: 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
Measured: Days 7, 35, and 63
Count of Participants With 4-fold Rise From Baseline in Immunoglobulin G (IgG) Antibodies in Antibody Lymphocyte Supernatant (ALS): Lipopolysaccharide (LPS) Antigen
Measured: 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
Measured: Days 7, 35, and 63
Geometric Mean Titer (GMT) of Immunoglobulin A (IgA) Antibodies in Serum: Invaplex Antigens
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.
Measured: Days 0, 7, 35, and 63
Geometric Mean Titer (GMT) of Immunoglobulin A (IgA) Antibodies in Serum: Lipopolysaccharide (LPS) Antigen
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.
Measured: Days 0, 7, 35, and 63
Geometric Mean Titer (GMT) of Immunoglobulin G (IgG) Antibodies in Serum: Invaplex Antigen
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.
Measured: Days 0, 7, 35, and 63
Geometric Mean Titer (GMT) of Immunoglobulin G (IgG) Antibodies in Serum: Lipopolysaccharide (LPS)
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.
Measured: Days 0, 7, 35, and 63
Geometric Mean Titer (GMT) of Immunoglobulin M (IgM) Antibodies in Serum: Invaplex Antigen
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.
Measured: Days 0, 7, 35, and 63
Geometric Mean Titer (GMT) of Immunoglobulin M (IgM) Antibodies in Serum: Lipopolysaccharide (LPS) Antigen
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.
Measured: Days 0, 7, 35, and 63
Geometric Mean Fold Change From Baseline in Immunoglobulin A (IgA) Antibodies in Serum: Invaplex Antigens
Measured: Baseline (Day 0, pre-vaccination) and Days 7, 35, and 63
Geometric Mean Fold Change From Baseline in Immunoglobulin A (IgA) Antibodies in Serum: Lipopolysaccharide (LPS) Antigen
Measured: Baseline (Day 0, pre-vaccination) and Days 7, 35, and 63
Geometric Mean Fold Change From Baseline in Immunoglobulin G (IgG) Antibodies in Serum: Invaplex Antigen
Measured: 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)
Measured: Baseline (Day 0, pre-vaccination) and Days 7, 35, and 63
Geometric Mean Fold Change From Baseline in Immunoglobulin M (IgM) Antibodies in Serum : Invaplex Antigen
Measured: 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
Measured: Baseline (Day 0, pre-vaccination) and Days 7, 35, and 63
Count of Participants With 4-fold Rise in Immunoglobulin A (IgA) Antibodies in Serum From Baseline: Invaplex Antigen
Measured: Days 7, 35, and 63
Count of Participants With 4-fold Rise in Immunoglobulin G (IgG) Antibodies in Serum From Baseline: Invaplex Antigen
Measured: Days 7, 35, and 63
Count of Participants With 4-fold Rise in Immunoglobulin M (IgM) Antibodies in Serum From Baseline: Invaplex Antigen
Measured: Days 7, 35, and 63
Count of Participants With 4-fold Rise in Immunoglobulin A (IgA) Antibodies in Serum From Baseline: Lipopolysaccharide (LPS) Antigen
Measured: Days 7, 35, and 63
Count of Participants With 4-fold Rise in Immunoglobulin G (IgG) Antibodies in Serum From Baseline: Lipopolysaccharide (LPS) Antigen
Measured: Days 7, 35, and 63
Count of Participants With 4-fold Rise in Immunoglobulin M (IgM) Antibodies in Serum From Baseline: Lipopolysaccharide (LPS) Antigen
Measured: Days 7, 35, and 63
Geometric Mean Titer (GMT) of Immunoglobulin A (IgA) Antibodies in Stool: Invaplex Antigen
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.
Measured: Days 0, 7, 28, 35, 56, 63, and 84
Geometric Mean Titer (GMT) of Immunoglobulin A (IgA) Antibodies in Stool: Lipopolysaccharide (LPS) Antigen
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.
Measured: Days 0, 7, 28, 35, 56, 63, and 84
Geometric Mean Fold Change From Baseline in Immunoglobulin A (IgA) Antibodies in Stool: Invaplex Antigens
Measured: 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
Measured: 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
Measured: Days 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
Measured: Days 7, 28, 35, 56, 63, and 84
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Oct 2016 (estimated)
- Study start23 Feb 2017
- Primary completion10 Jan 2018
- Study completion10 Jan 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for DiarrheaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- PATH
- Sponsor type
- University, hospital or other
- Collaborators
- International Centre for Diarrhoeal Disease Research, Bangladesh
- Responsible party
- Sponsor
- Investigators
- Rubhana Raqib, MD, Principal investigator, International Centre for Diarrhoeal Disease Research, Bangladesh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02934178
- Sponsor's protocol ID
- VAC-049
- Status last verified
- Mar 2020
- First submitted
- 30 Aug 2016
- Last updated
- 31 Mar 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 31 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT02934178
- Acronym / sponsor ID
- VAC-049
- Conditions
- Diarrhea
- Keywords
- shigellosis, Enterobacteriaceae Infections, Gram-Negative Bacterial Infections, Bacterial Infections, Gastroenteritis, Gastrointestinal Diseases, Digestive System Diseases, Intestinal Diseases
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- PATHUniversity, hospital or other
- Collaborators
- International Centre for Diarrhoeal Disease Research, Bangladesh
- Study start
- 23 Feb 2017 (actual)
- Primary completion
- 10 Jan 2018 (actual)
- Study completion
- 10 Jan 2018 (actual)
- First posted
- 14 Oct 2016 (estimated)
- Results
- Posted 31 Mar 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 8
| Arm | Type | Receives |
|---|---|---|
| Cohort 1: WRSS1 3 x 10³ CFU | Experimental | Biological: Shigella sonnei Strain WRSS1 VaccineHealthy toddlers receiving 3 oral doses of 3 x 10³ colony-forming units (CFU) of Shigella sonnei Strain WRSS1 approximately 4 weeks apart. |
| Cohort 2: WRSS1 3 x 10⁴ CFU | Experimental | Biological: Shigella sonnei Strain WRSS1 VaccineHealthy toddlers receiving 3 oral doses of 3 x 10⁴ CFU of Shigella sonnei Strain WRSS1 approximately 4 weeks apart. |
| Cohort 3: WRSS1 3 x 10⁵ CFU | Experimental | Biological: Shigella sonnei Strain WRSS1 VaccineHealthy toddlers receiving 3 oral doses of 3 x 10⁵ CFU of Shigella sonnei Strain WRSS1 approximately 4 weeks apart. |
| Cohort 4: WRSS1 3 x 10⁶ CFU | Experimental | Biological: Shigella sonnei Strain WRSS1 VaccineHealthy toddlers receiving 3 oral doses of 3 x 10⁶ CFU of Shigella sonnei Strain WRSS1 approximately 4 weeks apart. |
| Cohort 1: Placebo | Placebo comparator | Biological: PlaceboHealthy toddlers receiving 3 oral doses of placebo to match 3 x 10³ WRSS1 approximately 4 weeks apart. |
| Cohort 2: Placebo | Placebo comparator | Biological: PlaceboHealthy toddlers receiving 3 oral doses of placebo to match 3 x 10⁴ WRSS1 approximately 4 weeks apart. |
| Cohort 3: Placebo | Placebo comparator | Biological: PlaceboHealthy toddlers receiving 3 oral doses of placebo to match 3 x 10⁵ WRSS1 approximately 4 weeks apart. |
| Cohort 4: Placebo | Placebo comparator | Biological: PlaceboHealthy toddlers receiving 3 oral doses of placebo to match 3 x 10⁶ WRSS1 approximately 4 weeks apart. |
Who may qualify
- Ages
- 12 to 24 months
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (25 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Shigella sonnei Strain WRSS1 VaccineLive attenuated, oral Shigella WRSS1 vaccine | Biological | Cohort 1: WRSS1 3 x 10³ CFU, Cohort 2: WRSS1 3 x 10⁴ CFU, Cohort 3: WRSS1 3 x 10⁵ CFU, Cohort 4: WRSS1 3 x 10⁶ CFU |
| PlaceboSterile saline solution | Biological | Cohort 1: Placebo, Cohort 2: Placebo, Cohort 3: Placebo, Cohort 4: Placebo |
Primary outcome
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.
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.
42 secondary outcomes
Geometric Mean Titer (GMT) of Immunoglobulin A (IgA) Antibodies in Antibody Lymphocyte Supernatant (ALS): Invaplex Antigens
Time frame: Days 0, 7, 35, and 63
Geometric Mean Titer (GMT) of Immunoglobulin A (IgA) Antibodies in Lymphocyte Supernatant (ALS): Lipopolysaccharide (LPS) Antigen
Time frame: Days 0, 7, 35, and 63
Geometric Mean Titer (GMT) of Immunoglobulin G (IgG) Antibodies in Antibody Lymphocyte Supernatant (ALS): Invaplex Antigen
Time frame: Days 0, 7, 35, and 63
Geometric Mean Titer (GMT) of Immunoglobulin G (IgG) Antibodies in Antibody Lymphocyte Supernatant (ALS): Lipopolysaccharide (LPS)
Time frame: Days 0, 7, 35, and 63
Geometric Mean Titer (GMT) of Immunoglobulin M (IgM) Antibodies in Antibody Lymphocyte Supernatant (ALS): Invaplex Antigen
Time frame: Days 0, 7, 35, and 63
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
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
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
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
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
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
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
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
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
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
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
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
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
Geometric Mean Titer (GMT) of Immunoglobulin A (IgA) Antibodies in Serum: Invaplex Antigens
Time frame: Days 0, 7, 35, and 63
Geometric Mean Titer (GMT) of Immunoglobulin A (IgA) Antibodies in Serum: Lipopolysaccharide (LPS) Antigen
Time frame: Days 0, 7, 35, and 63
Geometric Mean Titer (GMT) of Immunoglobulin G (IgG) Antibodies in Serum: Invaplex Antigen
Time frame: Days 0, 7, 35, and 63
Geometric Mean Titer (GMT) of Immunoglobulin G (IgG) Antibodies in Serum: Lipopolysaccharide (LPS)
Time frame: Days 0, 7, 35, and 63
Geometric Mean Titer (GMT) of Immunoglobulin M (IgM) Antibodies in Serum: Invaplex Antigen
Time frame: Days 0, 7, 35, and 63
Geometric Mean Titer (GMT) of Immunoglobulin M (IgM) Antibodies in Serum: Lipopolysaccharide (LPS) Antigen
Time frame: Days 0, 7, 35, and 63
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
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
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
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
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
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
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
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
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
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
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
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
Geometric Mean Titer (GMT) of Immunoglobulin A (IgA) Antibodies in Stool: Invaplex Antigen
Time frame: Days 0, 7, 28, 35, 56, 63, and 84
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
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
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Mar 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Rubhana Raqib, MD principal investigator
International Centre for Diarrhoeal Disease Research, Bangladesh
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Shigella sonnei Strain WRSS1 Vaccine in people with Diarrhea, run by PATH at 1 site in Bangladesh.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 31 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Bangladesh. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 31 Mar 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum Severity of Reactogenicity by Vaccination (time frame: 72 hours after each vaccination (Day 3, Day 31, Day 59)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Mar 2020.