Trial Outcomes & Findings for Safety Study of Live Attenuated Oral Shigella (WRSS1) Vaccine in Bangladeshi Adults and Children (NCT NCT01813071)

Results Overview

Based on maximum severity per participant over all serious adverse events (SAEs) within 6 months of any vaccination. A Serious Adverse Event, including serious suspected adverse reaction or serious adverse reaction as determined by the Investigator or the sponsor, was any event that results in any of the following outcomes: Inpatient hospitalization or prolongation of existing hospitalization , life-threatening AE that in the opinion of the investigator or sponsor put the participant at immediate risk of death, persistent or significant incapacity or substantial disruption, congenital abnormality or birth defect, a medically important event that may have jeopardized the participant or may have required intervention to prevent one of the other outcomes listed or death.

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

103 participants

Primary outcome timeframe

Day -1(admission day) through 6 months (Day 224 +/- 14 days) after the third vaccination for Cohorts A2,A3, B2, B3, B4, and after the first vaccination (Day 168 +/- 14 days) for Cohorts A1 and B1.

Results posted on

2019-02-08

Participant Flow

Participants in general good health were recruited, screened and consented at the icddr,b Dhaka in Bangladesh. Final eligibility was determined by fulfillment of all the inclusion and absence of any of the exclusion criteria. Adults were enrolled August 23, 2013 to November 10, 2013 and children were enrolled April 27, 2014 to August 9, 2015.

Participant milestones

Participant milestones
Measure	Part A (Adults): Cohort A1 One oral dose of \~3x10\^4 cfu WRSS1	Part A (Adults): Cohort A2 Three oral doses of \~3x10\^5 cfu WRSS1	Part A (Adults): Cohort A3 Three oral doses of \~3x10\^6 cfu WRSS1	Part A (Adults): Placebo One or Three oral doses of Placebo	Part B (Children): Cohort B1 One oral dose of \~3x10\^3 cfu WRSS1	Part B (Children): Cohort B2 Three oral doses of \~3x10\^4 cfu WRSS1	Part B (Children): Cohort B3 Three oral doses of \~3x10\^5 cfu WRSS1	Part B (Children): Cohort B4 Three oral doses of \~3x10\^6 cfu WRSS1	Part B (Children): Placebo One or three oral doses of Placebo
Overall Study STARTED	10	10	10	9	12	12	12	12	16
Overall Study COMPLETED	10	10	10	9	11	5	9	7	13
Overall Study NOT COMPLETED	0	0	0	0	1	7	3	5	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Part B (Children): Cohort B1 One oral dose of \~3x10\^3 cfu WRSS1	Part B (Children): Cohort B2 Three oral doses of \~3x10\^4 cfu WRSS1	Part B (Children): Cohort B3 Three oral doses of \~3x10\^5 cfu WRSS1	Part B (Children): Cohort B4 Three oral doses of \~3x10\^6 cfu WRSS1	Part B (Children): Placebo One or three oral doses of Placebo
Overall Study Protocol Violation	1	4	2	4	2
Overall Study Withdrawal by Subject	0	1	0	0	0
Overall Study Adverse Event	0	1	0	0	0
Overall Study Physician Decision	0	0	1	0	0
Overall Study Met inc/exc criteria	0	1	0	1	1

Baseline Characteristics

Additional row added to stratify participants by 'adults' and 'children' and give totals for each.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Part A (Adults): Cohort A1 n=10 Participants One oral dose of \~3x10\^4 cfu WRSS1	Part A (Adults): Cohort A2 n=10 Participants Three oral doses of \~3x10\^5 cfu WRSS1	Part A (Adults): Cohort A3 n=10 Participants Three oral doses of \~3x10\^6 cfu WRSS1	Part A (Adults): Placebo n=9 Participants One or Three oral doses of Placebo	Part B (Children): Cohort B1 n=12 Participants One oral dose of \~3x10\^3 cfu WRSS1	Part B (Children): Cohort B2 n=12 Participants Three oral doses of \~3x10\^4 cfu WRSS1	Part B (Children): Cohort B3 n=12 Participants Three oral doses of \~3x10\^5 cfu WRSS1	Part B (Children): Cohort B4 n=12 Participants Three oral doses of \~3x10\^6 cfu WRSS1	Part B (Children): Placebo n=16 Participants One or three oral doses of Placebo	Total n=103 Participants Total of all reporting groups
Age, Continuous Part A Adults	25.7 years STANDARD_DEVIATION 5.23 • n=10 Participants • Additional row added to stratify participants by 'adults' and 'children' and give totals for each.	28.1 years STANDARD_DEVIATION 5.51 • n=10 Participants • Additional row added to stratify participants by 'adults' and 'children' and give totals for each.	27.0 years STANDARD_DEVIATION 2.67 • n=10 Participants • Additional row added to stratify participants by 'adults' and 'children' and give totals for each.	27.4 years STANDARD_DEVIATION 5.34 • n=9 Participants • Additional row added to stratify participants by 'adults' and 'children' and give totals for each.	—	—	—	—	—	27.1 years STANDARD_DEVIATION 4.71 • n=39 Participants • Additional row added to stratify participants by 'adults' and 'children' and give totals for each.
Age, Continuous Part B Children	—	—	—	—	6.3 years STANDARD_DEVIATION 0.98 • n=12 Participants • Additional row added to stratify participants by 'adults' and 'children' and give totals for each.	6.6 years STANDARD_DEVIATION 1.16 • n=12 Participants • Additional row added to stratify participants by 'adults' and 'children' and give totals for each.	6.0 years STANDARD_DEVIATION 0.85 • n=12 Participants • Additional row added to stratify participants by 'adults' and 'children' and give totals for each.	6.3 years STANDARD_DEVIATION 0.97 • n=12 Participants • Additional row added to stratify participants by 'adults' and 'children' and give totals for each.	6.6 years STANDARD_DEVIATION 1.02 • n=16 Participants • Additional row added to stratify participants by 'adults' and 'children' and give totals for each.	6.4 years STANDARD_DEVIATION 1.00 • n=64 Participants • Additional row added to stratify participants by 'adults' and 'children' and give totals for each.
Sex: Female, Male Female	5 Participants n=10 Participants	5 Participants n=10 Participants	7 Participants n=10 Participants	4 Participants n=9 Participants	8 Participants n=12 Participants	8 Participants n=12 Participants	9 Participants n=12 Participants	5 Participants n=12 Participants	12 Participants n=16 Participants	63 Participants n=103 Participants
Sex: Female, Male Male	5 Participants n=10 Participants	5 Participants n=10 Participants	3 Participants n=10 Participants	5 Participants n=9 Participants	4 Participants n=12 Participants	4 Participants n=12 Participants	3 Participants n=12 Participants	7 Participants n=12 Participants	4 Participants n=16 Participants	40 Participants n=103 Participants
Race and Ethnicity Not Collected	—	—	—	—	—	—	—	—	—	0 Participants Race and Ethnicity were not collected from any participant.
Region of Enrollment Bangladesh	10 participants n=10 Participants	10 participants n=10 Participants	10 participants n=10 Participants	9 participants n=9 Participants	12 participants n=12 Participants	12 participants n=12 Participants	12 participants n=12 Participants	12 participants n=12 Participants	16 participants n=16 Participants	103 participants n=103 Participants
Height (cm) Part A Adults	160.7 centimeters STANDARD_DEVIATION 10.75 • n=10 Participants • Additional row added to stratify participants by 'adults' and 'children' and give totals for each.	160.1 centimeters STANDARD_DEVIATION 9.47 • n=10 Participants • Additional row added to stratify participants by 'adults' and 'children' and give totals for each.	157.0 centimeters STANDARD_DEVIATION 6.36 • n=10 Participants • Additional row added to stratify participants by 'adults' and 'children' and give totals for each.	159.2 centimeters STANDARD_DEVIATION 10.07 • n=9 Participants • Additional row added to stratify participants by 'adults' and 'children' and give totals for each.	—	—	—	—	—	159.3 centimeters STANDARD_DEVIATION 9.03 • n=39 Participants • Additional row added to stratify participants by 'adults' and 'children' and give totals for each.
Height (cm) Part B Children	—	—	—	—	116.4 centimeters STANDARD_DEVIATION 4.66 • n=12 Participants • Additional row added to stratify participants by 'adults' and 'children' and give totals for each.	116.4 centimeters STANDARD_DEVIATION 8.32 • n=12 Participants • Additional row added to stratify participants by 'adults' and 'children' and give totals for each.	115.0 centimeters STANDARD_DEVIATION 4.86 • n=12 Participants • Additional row added to stratify participants by 'adults' and 'children' and give totals for each.	121.0 centimeters STANDARD_DEVIATION 6.74 • n=12 Participants • Additional row added to stratify participants by 'adults' and 'children' and give totals for each.	119.4 centimeters STANDARD_DEVIATION 7.91 • n=16 Participants • Additional row added to stratify participants by 'adults' and 'children' and give totals for each.	117.8 centimeters STANDARD_DEVIATION 6.90 • n=64 Participants • Additional row added to stratify participants by 'adults' and 'children' and give totals for each.
Weight (kg) Part A (Adults)	67.3 kilograms STANDARD_DEVIATION 13.98 • n=10 Participants • Additional row added to stratify participants by 'adults' and 'children' and give totals for each	58.1 kilograms STANDARD_DEVIATION 11.52 • n=10 Participants • Additional row added to stratify participants by 'adults' and 'children' and give totals for each	54.5 kilograms STANDARD_DEVIATION 8.43 • n=10 Participants • Additional row added to stratify participants by 'adults' and 'children' and give totals for each	56.4 kilograms STANDARD_DEVIATION 11.52 • n=9 Participants • Additional row added to stratify participants by 'adults' and 'children' and give totals for each	—	—	—	—	—	59.2 kilograms STANDARD_DEVIATION 12.16 • n=39 Participants • Additional row added to stratify participants by 'adults' and 'children' and give totals for each
Weight (kg) Part B (Children)	—	—	—	—	19.7 kilograms STANDARD_DEVIATION 1.64 • n=12 Participants • Additional row added to stratify participants by 'adults' and 'children' and give totals for each	20.5 kilograms STANDARD_DEVIATION 4.09 • n=12 Participants • Additional row added to stratify participants by 'adults' and 'children' and give totals for each	21.3 kilograms STANDARD_DEVIATION 4.26 • n=12 Participants • Additional row added to stratify participants by 'adults' and 'children' and give totals for each	22.9 kilograms STANDARD_DEVIATION 4.62 • n=12 Participants • Additional row added to stratify participants by 'adults' and 'children' and give totals for each	21.0 kilograms STANDARD_DEVIATION 3.81 • n=16 Participants • Additional row added to stratify participants by 'adults' and 'children' and give totals for each	21.1 kilograms STANDARD_DEVIATION 3.85 • n=64 Participants • Additional row added to stratify participants by 'adults' and 'children' and give totals for each

PRIMARY outcome

Timeframe: Day -1(admission day) through 6 months (Day 224 +/- 14 days) after the third vaccination for Cohorts A2,A3, B2, B3, B4, and after the first vaccination (Day 168 +/- 14 days) for Cohorts A1 and B1.

Population: All participants who had been exposed to at least one dose of study product were included in the primary analysis for safety.

Based on maximum severity per participant over all serious adverse events (SAEs) within 6 months of any vaccination. A Serious Adverse Event, including serious suspected adverse reaction or serious adverse reaction as determined by the Investigator or the sponsor, was any event that results in any of the following outcomes: Inpatient hospitalization or prolongation of existing hospitalization , life-threatening AE that in the opinion of the investigator or sponsor put the participant at immediate risk of death, persistent or significant incapacity or substantial disruption, congenital abnormality or birth defect, a medically important event that may have jeopardized the participant or may have required intervention to prevent one of the other outcomes listed or death.

Outcome measures

Outcome measures
Measure	Part B (Children): Placebo n=12 Participants One or three oral doses of Placebo	Part B (Children): Cohort B1 n=12 Participants One oral dose of \~3x10\^3 cfu WRSS1	Part A (Adults): Cohort A3 n=10 Participants Three oral doses of \~3x10\^6 cfu WRSS1	Part A (Adults): Placebo n=9 Participants One or Three oral doses of Placebo	Part A (Adults): Cohort A1 n=10 Participants One oral dose of \~3x10\^4 cfu WRSS1	Part A (Adults): Cohort A2 n=10 Participants Three oral doses of \~3x10\^5 cfu WRSS1	Part B (Children): Cohort B3 n=12 Participants Three oral doses of \~3x10\^5 cfu WRSS1	Part B (Children): Cohort B4 n=12 Participants Three oral doses of \~3x10\^6 cfu WRSS1	Part B (Children): Placebo n=16 Participants One or three oral doses of Placebo
Number and Percentage of Participants With Serious Adverse Events (SAEs)	1 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	1 Participants

PRIMARY outcome

Timeframe: Day -1(admission day) through 6 months (Day 224 +/- 14 days) after the third vaccination for Cohorts A2,A3, B2, B3, B4, and after the first vaccination (Day 168 +/- 14 days) for Cohorts A1 and B1.

Population: All participants who had been exposed to at least one dose of study product were included in the primary analysis for safety.

Based on subject count over all non-serious adverse events. An Adverse event was defined as any untoward medical occurrence in humans, whether or not considered drug related, that occurred during the conduct of a clinical trial. Any change in clinical status, ECGs, routine labs, x-rays, physical examinations, etc., that was considered clinically significant by the study investigator, was considered an AE. This definition also included an exacerbation or worsening of pre-existing conditions or events, inter-current illnesses, injuries, or vaccine or drug interaction, or worsening of abnormal clinical laboratory values. All AEs were assessed by the clinician using a protocol defined grading system.

Outcome measures

Outcome measures
Measure	Part B (Children): Placebo n=12 Participants One or three oral doses of Placebo	Part B (Children): Cohort B1 n=12 Participants One oral dose of \~3x10\^3 cfu WRSS1	Part A (Adults): Cohort A3 n=10 Participants Three oral doses of \~3x10\^6 cfu WRSS1	Part A (Adults): Placebo n=9 Participants One or Three oral doses of Placebo	Part A (Adults): Cohort A1 n=10 Participants One oral dose of \~3x10\^4 cfu WRSS1	Part A (Adults): Cohort A2 n=10 Participants Three oral doses of \~3x10\^5 cfu WRSS1	Part B (Children): Cohort B3 n=12 Participants Three oral doses of \~3x10\^5 cfu WRSS1	Part B (Children): Cohort B4 n=12 Participants Three oral doses of \~3x10\^6 cfu WRSS1	Part B (Children): Placebo n=16 Participants One or three oral doses of Placebo
Number and Percentage of Participants With Any Non-serious Unsolicited Adverse Events	10 Participants	9 Participants	8 Participants	6 Participants	8 Participants	7 Participants	9 Participants	12 Participants	12 Participants

PRIMARY outcome

Timeframe: Day 0 through Day 7 after any vaccination

Population: All participants who had been exposed to at least one dose of study product were included in the primary analysis for safety.

Maximum severity per participant of any systemic or any gastrointestinal reactogenicity recorded within 7 days of any vaccination is reported. Solicited Systemic reactogenicity events assessed included fever, headache, malaise, generalized myalgia, arthralgia, chills, reactive arthritis and decreased appetite. Intestinal solicited reactogenicity events assessed included abdominal cramps, abdominal pain, nausea, vomiting, loose stool, diarrhea, dysentery, bloating, excess flatulence and constipation. Diarrhea and dysentery were assessed both during inpatient (first three day period post-vaccination) and outpatient ( post-vaccination days 4-7) periods post-vaccination 1. Vaccinations 2 and 3 did not have an inpatient admission period for any participants. Diarrhea severity was determined on the basis of stool number, grading and stool weight during the inpatient period and by stool number and grading only during the outpatient period.

Outcome measures

Outcome measures
Measure	Part B (Children): Placebo n=12 Participants One or three oral doses of Placebo	Part B (Children): Cohort B1 n=12 Participants One oral dose of \~3x10\^3 cfu WRSS1	Part A (Adults): Cohort A3 n=10 Participants Three oral doses of \~3x10\^6 cfu WRSS1	Part A (Adults): Placebo n=9 Participants One or Three oral doses of Placebo	Part A (Adults): Cohort A1 n=10 Participants One oral dose of \~3x10\^4 cfu WRSS1	Part A (Adults): Cohort A2 n=10 Participants Three oral doses of \~3x10\^5 cfu WRSS1	Part B (Children): Cohort B3 n=12 Participants Three oral doses of \~3x10\^5 cfu WRSS1	Part B (Children): Cohort B4 n=12 Participants Three oral doses of \~3x10\^6 cfu WRSS1	Part B (Children): Placebo n=16 Participants One or three oral doses of Placebo
Number and Percentage of Participants With Solicited Systemic and Intestinal Reactions Any Systemic Reactogenicity	0 Participants	3 Participants	6 Participants	4 Participants	2 Participants	1 Participants	0 Participants	4 Participants	2 Participants
Number and Percentage of Participants With Solicited Systemic and Intestinal Reactions Any Gastrointestinal Reactogenicity	2 Participants	4 Participants	7 Participants	4 Participants	2 Participants	4 Participants	3 Participants	6 Participants	2 Participants

PRIMARY outcome

Timeframe: SAEs at any time and AEs after any vaccination until Day 168 (Cohort A1, B1) and Day 224 (all other Cohorts).

Population: All participants who had been exposed to at least one dose of study product were included in the primary analysis for safety. Adult Cohort A1 and Child Cohort B1 only received a single dose of study vaccine.

Adverse event (AE) was defined as any untoward medical occurrence in humans, whether or not considered drug related, that occurs during the conduct of a clinical trial. A Serious Adverse Event (SAE) , including serious suspected adverse reaction or serious adverse reaction as determined by the Investigator or the sponsor, was any event that results in any of the following outcomes: Inpatient hospitalization or prolongation of existing hospitalization , life-threatening AE that in the opinion of the investigator or sponsor put the participant at immediate risk of death, persistent or significant incapacity or substantial disruption, congenital abnormality or birth defect, a medically important event that may have jeopardized the participant or may have required intervention to prevent one of the other outcomes listed or death. Causality of the AE/SAE to the study drug was assessed by the Investigator as reasonable possibility that the study product caused the reported event.