Trial Outcomes & Findings for The Effects of Increased Inoculum on Oral Rotavirus Vaccine Take and Immunogenicity (NCT NCT02992197)

Last Updated: 2020-08-04

Results Overview

This will be an aggregate measure demonstrating a change from baseline. Infants will have stool collected immediately prior to Rotarix vaccination at weeks 6 and 10 of life, then 4, 7, and 14 days following each dose (i.e. last assessment at week 12 of life). Each specimen will be assessed for vaccine-strain virus (i.e. fecal vaccine shedding) at each time point by polymerase chain reaction. Any child who has a change in fecal vaccine shedding status, from negative at baseline (6 weeks) to positive at any subsequent time point, will be categorized as having met the outcome measure for positive fecal vaccine shedding.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

220 participants

Primary outcome timeframe

Measured through week 12 of life

Results posted on

2020-08-04

Participant Flow

Participant milestones

Participant milestones
Measure	Rotarix, Single Dose Rotarix 1.5 mL (standard single dose) and 1.5 mL of placebo by mouth (sterile, pharmacy-grade water) at both 6 and 10 weeks of life Rotarix, dose 1: Rotarix, dose 1 Placebo (for Rotarix dose 2): Sterile water to provide volume equivalent as a second dose of Rotarix	Rotarix, Double Dose Rotarix 3 mL by mouth (two standard doses administered simultaneously) at both 6 and 10 weeks of life Rotarix, dose 1: Rotarix, dose 1 Rotarix, dose 2: Rotarix, dose 2
Overall Study STARTED	110	110
Overall Study COMPLETED	99	103
Overall Study NOT COMPLETED	11	7

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Rotarix, Single Dose n=97 Participants Rotarix 1.5 mL (standard single dose) and 1.5 mL of placebo by mouth (sterile, pharmacy-grade water) at both 6 and 10 weeks of life Rotarix, dose 1: Rotarix, dose 1 Placebo (for Rotarix dose 2): Sterile water to provide volume equivalent as a second dose of Rotarix	Rotarix, Double Dose n=92 Participants Rotarix 3 mL by mouth (two standard doses administered simultaneously) at both 6 and 10 weeks of life Rotarix, dose 1: Rotarix, dose 1 Rotarix, dose 2: Rotarix, dose 2	Total n=189 Participants Total of all reporting groups
Age, Categorical <=18 years	97 Participants n=97 Participants	92 Participants n=92 Participants	189 Participants n=189 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=97 Participants	0 Participants n=92 Participants	0 Participants n=189 Participants
Age, Categorical >=65 years	0 Participants n=97 Participants	0 Participants n=92 Participants	0 Participants n=189 Participants
Age, Continuous	4.8 days STANDARD_DEVIATION 1.8 • n=97 Participants	5.0 days STANDARD_DEVIATION 1.8 • n=92 Participants	4.9 days STANDARD_DEVIATION 1.8 • n=189 Participants
Sex: Female, Male Female	51 Participants n=97 Participants	41 Participants n=92 Participants	92 Participants n=189 Participants
Sex: Female, Male Male	46 Participants n=97 Participants	51 Participants n=92 Participants	97 Participants n=189 Participants
Race and Ethnicity Not Collected	—	—	0 Participants Race and Ethnicity were not collected from any participant.
Region of Enrollment Bangladesh	97 participants n=97 Participants	92 participants n=92 Participants	189 participants n=189 Participants
Birth place Home birth	19 Participants n=97 Participants	25 Participants n=92 Participants	44 Participants n=189 Participants
Birth place Hospital/clinic birth	78 Participants n=97 Participants	67 Participants n=92 Participants	145 Participants n=189 Participants
Mode of delivery Vaginal	55 Participants n=97 Participants	50 Participants n=92 Participants	105 Participants n=189 Participants
Mode of delivery Caesarean section	42 Participants n=97 Participants	42 Participants n=92 Participants	84 Participants n=189 Participants
Weight	2.81 kg STANDARD_DEVIATION 0.44 • n=97 Participants	2.86 kg STANDARD_DEVIATION 0.38 • n=92 Participants	2.83 kg STANDARD_DEVIATION 0.42 • n=189 Participants
Length	48.9 cm STANDARD_DEVIATION 2.6 • n=97 Participants	48.7 cm STANDARD_DEVIATION 0.21 • n=92 Participants	48.8 cm STANDARD_DEVIATION 2.2 • n=189 Participants
Head circumference	34.1 cm STANDARD_DEVIATION 1.3 • n=97 Participants	34.2 cm STANDARD_DEVIATION 1.3 • n=92 Participants	34.1 cm STANDARD_DEVIATION 1.3 • n=189 Participants
Water treatment None	24 Participants n=97 Participants	29 Participants n=92 Participants	53 Participants n=189 Participants
Water treatment Water filter	4 Participants n=97 Participants	2 Participants n=92 Participants	6 Participants n=189 Participants
Water treatment Boil	69 Participants n=97 Participants	61 Participants n=92 Participants	130 Participants n=189 Participants
Type of toilet Septic tank or toilet	52 Participants n=97 Participants	45 Participants n=92 Participants	97 Participants n=189 Participants
Type of toilet Water-sealed or slab latrine	41 Participants n=97 Participants	44 Participants n=92 Participants	85 Participants n=189 Participants
Type of toilet Pit latrine or open latrine	4 Participants n=97 Participants	3 Participants n=92 Participants	7 Participants n=189 Participants
Type of toilet Open drain beside home	44 Participants n=97 Participants	55 Participants n=92 Participants	99 Participants n=189 Participants
Family demographics Mother's education <= secondary	81 Participants n=97 Participants	74 Participants n=92 Participants	155 Participants n=189 Participants
Family demographics Father's education <= secondary	71 Participants n=97 Participants	72 Participants n=92 Participants	143 Participants n=189 Participants
Family demographics Homeowner	43 Participants n=97 Participants	32 Participants n=92 Participants	75 Participants n=189 Participants
Family demographics Any food deficit	31 Participants n=97 Participants	37 Participants n=92 Participants	68 Participants n=189 Participants
Family demographics Municipal (piped) water source	93 Participants n=97 Participants	80 Participants n=92 Participants	173 Participants n=189 Participants
Monthly household income in Taka	15000 Taka n=97 Participants	15000 Taka n=92 Participants	15000 Taka n=189 Participants

PRIMARY outcome

Timeframe: Measured through week 12 of life

Outcome measures

Outcome measures
Measure	Rotarix, Single Dose n=97 Participants Rotarix 1.5 mL (standard single dose) and 1.5 mL of placebo by mouth (sterile, pharmacy-grade water) at both 6 and 10 weeks of life Rotarix, dose 1: Rotarix, dose 1 Placebo (for Rotarix dose 2): Sterile water to provide volume equivalent as a second dose of Rotarix	Rotarix, Double Dose n=92 Participants Rotarix 3 mL by mouth (two standard doses administered simultaneously) at both 6 and 10 weeks of life Rotarix, dose 1: Rotarix, dose 1 Rotarix, dose 2: Rotarix, dose 2
Number (or Percentage) of Infants in Each Study Arm Who Test Positive for Fecal Rotavirus Vaccine-strain Virus Shedding Post-vaccination	63 Participants	55 Participants

PRIMARY outcome

Timeframe: Measured at week 14 of life

This outcome will measure seroconversion, i.e. the change in plasma rotavirus-specific IgA concentration at week 14 of life compared to week 6 of life (baseline). Blood will be collected from infants prior to the first dose of Rotarix at week 6 of life and again at week 14 of life (4 weeks following the second dose) for measurement of plasma rotavirus-specific IgA by enzyme immunoassay. Infants will be assessed for seroconversion (IgA concentration \<=20 U/mL pre-vaccination and \>20 post-vaccination). Infants who demonstrate rotavirus-specific IgA seroconversion will be categorized as having met the outcome measure.

Outcome measures

Outcome measures
Measure	Rotarix, Single Dose n=97 Participants Rotarix 1.5 mL (standard single dose) and 1.5 mL of placebo by mouth (sterile, pharmacy-grade water) at both 6 and 10 weeks of life Rotarix, dose 1: Rotarix, dose 1 Placebo (for Rotarix dose 2): Sterile water to provide volume equivalent as a second dose of Rotarix	Rotarix, Double Dose n=92 Participants Rotarix 3 mL by mouth (two standard doses administered simultaneously) at both 6 and 10 weeks of life Rotarix, dose 1: Rotarix, dose 1 Rotarix, dose 2: Rotarix, dose 2
Number (or Percentage) of Infants in Each Study Arm With Rotavirus-specific Plasma Immunoglobulin A (IgA) Seroconversion Post-vaccination	41 Participants	42 Participants

PRIMARY outcome

Timeframe: Measured at week 14 of life

Vaccine take is an aggregate, dichotomous immunogenicity measure (successful vaccine take vs no vaccine take). Infants positive for either fecal vaccine shedding OR plasma rotavirus-specific IgA seroconversion (as described in Outcomes 1 and 2, respectively) will be categorized as having met the outcome measure of successful vaccine take. Those who met neither outcome will be categorized as no vaccine take.

Outcome measures

Outcome measures
Measure	Rotarix, Single Dose n=97 Participants Rotarix 1.5 mL (standard single dose) and 1.5 mL of placebo by mouth (sterile, pharmacy-grade water) at both 6 and 10 weeks of life Rotarix, dose 1: Rotarix, dose 1 Placebo (for Rotarix dose 2): Sterile water to provide volume equivalent as a second dose of Rotarix	Rotarix, Double Dose n=92 Participants Rotarix 3 mL by mouth (two standard doses administered simultaneously) at both 6 and 10 weeks of life Rotarix, dose 1: Rotarix, dose 1 Rotarix, dose 2: Rotarix, dose 2
Number (or Percentage) of Infants in Each Study Arm With Successful Vaccine Take, Defined as Positive Fecal Vaccine Shedding Post-vaccination OR Rotavirus-specific Plasma IgA Seroconversion Post-vaccination	69 Participants	62 Participants

Adverse Events

Rotarix, Single Dose

Serious events: 2 serious events

Other events: 28 other events

Deaths: 0 deaths

Rotarix, Double Dose

Serious events: 4 serious events

Other events: 31 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Rotarix, Single Dose n=107 participants at risk；n=110 participants at risk Rotarix 1.5 mL (standard single dose) and 1.5 mL of placebo by mouth (sterile, pharmacy-grade water) at both 6 and 10 weeks of life Rotarix, dose 1: Rotarix, dose 1 Placebo (for Rotarix dose 2): Sterile water to provide volume equivalent as a second dose of Rotarix	Rotarix, Double Dose n=106 participants at risk；n=110 participants at risk Rotarix 3 mL by mouth (two standard doses administered simultaneously) at both 6 and 10 weeks of life Rotarix, dose 1: Rotarix, dose 1 Rotarix, dose 2: Rotarix, dose 2
Gastrointestinal disorders Diarrhea	0.91% 1/110 • Number of events 2 • Enrollment (<7 days of life) through week 14 study visit (4 months) for serious adverse events; week 6 visit (first vaccine dose) through Week 14 visit + 3 days (end of participation) for all other AEs (2 months) Serious adverse events were recorded from study enrollment (\<7 days of life) but all other adverse events were only recorded starting from the first study intervention (at the week 6 clinic visit), the total numbers of children evaluated for serious adverse events (which is based on study enrollment) differs from those evaluated for adverse events (which is based on the number of children dosed starting at week 6 of life, and is less due to attrition between enrollment and first dosing).	1.8% 2/110 • Number of events 4 • Enrollment (<7 days of life) through week 14 study visit (4 months) for serious adverse events; week 6 visit (first vaccine dose) through Week 14 visit + 3 days (end of participation) for all other AEs (2 months) Serious adverse events were recorded from study enrollment (\<7 days of life) but all other adverse events were only recorded starting from the first study intervention (at the week 6 clinic visit), the total numbers of children evaluated for serious adverse events (which is based on study enrollment) differs from those evaluated for adverse events (which is based on the number of children dosed starting at week 6 of life, and is less due to attrition between enrollment and first dosing).
Infections and infestations Sepsis	0.91% 1/110 • Number of events 1 • Enrollment (<7 days of life) through week 14 study visit (4 months) for serious adverse events; week 6 visit (first vaccine dose) through Week 14 visit + 3 days (end of participation) for all other AEs (2 months) Serious adverse events were recorded from study enrollment (\<7 days of life) but all other adverse events were only recorded starting from the first study intervention (at the week 6 clinic visit), the total numbers of children evaluated for serious adverse events (which is based on study enrollment) differs from those evaluated for adverse events (which is based on the number of children dosed starting at week 6 of life, and is less due to attrition between enrollment and first dosing).	0.00% 0/110 • Enrollment (<7 days of life) through week 14 study visit (4 months) for serious adverse events; week 6 visit (first vaccine dose) through Week 14 visit + 3 days (end of participation) for all other AEs (2 months) Serious adverse events were recorded from study enrollment (\<7 days of life) but all other adverse events were only recorded starting from the first study intervention (at the week 6 clinic visit), the total numbers of children evaluated for serious adverse events (which is based on study enrollment) differs from those evaluated for adverse events (which is based on the number of children dosed starting at week 6 of life, and is less due to attrition between enrollment and first dosing).
Gastrointestinal disorders Subacute intestinal obstruction	0.00% 0/110 • Enrollment (<7 days of life) through week 14 study visit (4 months) for serious adverse events; week 6 visit (first vaccine dose) through Week 14 visit + 3 days (end of participation) for all other AEs (2 months) Serious adverse events were recorded from study enrollment (\<7 days of life) but all other adverse events were only recorded starting from the first study intervention (at the week 6 clinic visit), the total numbers of children evaluated for serious adverse events (which is based on study enrollment) differs from those evaluated for adverse events (which is based on the number of children dosed starting at week 6 of life, and is less due to attrition between enrollment and first dosing).	0.91% 1/110 • Number of events 1 • Enrollment (<7 days of life) through week 14 study visit (4 months) for serious adverse events; week 6 visit (first vaccine dose) through Week 14 visit + 3 days (end of participation) for all other AEs (2 months) Serious adverse events were recorded from study enrollment (\<7 days of life) but all other adverse events were only recorded starting from the first study intervention (at the week 6 clinic visit), the total numbers of children evaluated for serious adverse events (which is based on study enrollment) differs from those evaluated for adverse events (which is based on the number of children dosed starting at week 6 of life, and is less due to attrition between enrollment and first dosing).
Respiratory, thoracic and mediastinal disorders Diaphragmatic hernia	0.00% 0/110 • Enrollment (<7 days of life) through week 14 study visit (4 months) for serious adverse events; week 6 visit (first vaccine dose) through Week 14 visit + 3 days (end of participation) for all other AEs (2 months) Serious adverse events were recorded from study enrollment (\<7 days of life) but all other adverse events were only recorded starting from the first study intervention (at the week 6 clinic visit), the total numbers of children evaluated for serious adverse events (which is based on study enrollment) differs from those evaluated for adverse events (which is based on the number of children dosed starting at week 6 of life, and is less due to attrition between enrollment and first dosing).	0.91% 1/110 • Number of events 1 • Enrollment (<7 days of life) through week 14 study visit (4 months) for serious adverse events; week 6 visit (first vaccine dose) through Week 14 visit + 3 days (end of participation) for all other AEs (2 months) Serious adverse events were recorded from study enrollment (\<7 days of life) but all other adverse events were only recorded starting from the first study intervention (at the week 6 clinic visit), the total numbers of children evaluated for serious adverse events (which is based on study enrollment) differs from those evaluated for adverse events (which is based on the number of children dosed starting at week 6 of life, and is less due to attrition between enrollment and first dosing).

Other adverse events

Other adverse events
Measure	Rotarix, Single Dose n=107 participants at risk；n=110 participants at risk Rotarix 1.5 mL (standard single dose) and 1.5 mL of placebo by mouth (sterile, pharmacy-grade water) at both 6 and 10 weeks of life Rotarix, dose 1: Rotarix, dose 1 Placebo (for Rotarix dose 2): Sterile water to provide volume equivalent as a second dose of Rotarix	Rotarix, Double Dose n=106 participants at risk；n=110 participants at risk Rotarix 3 mL by mouth (two standard doses administered simultaneously) at both 6 and 10 weeks of life Rotarix, dose 1: Rotarix, dose 1 Rotarix, dose 2: Rotarix, dose 2
Gastrointestinal disorders Diarrhea	16.8% 18/107 • Number of events 20 • Enrollment (<7 days of life) through week 14 study visit (4 months) for serious adverse events; week 6 visit (first vaccine dose) through Week 14 visit + 3 days (end of participation) for all other AEs (2 months) Serious adverse events were recorded from study enrollment (\<7 days of life) but all other adverse events were only recorded starting from the first study intervention (at the week 6 clinic visit), the total numbers of children evaluated for serious adverse events (which is based on study enrollment) differs from those evaluated for adverse events (which is based on the number of children dosed starting at week 6 of life, and is less due to attrition between enrollment and first dosing).	15.1% 16/106 • Number of events 17 • Enrollment (<7 days of life) through week 14 study visit (4 months) for serious adverse events; week 6 visit (first vaccine dose) through Week 14 visit + 3 days (end of participation) for all other AEs (2 months) Serious adverse events were recorded from study enrollment (\<7 days of life) but all other adverse events were only recorded starting from the first study intervention (at the week 6 clinic visit), the total numbers of children evaluated for serious adverse events (which is based on study enrollment) differs from those evaluated for adverse events (which is based on the number of children dosed starting at week 6 of life, and is less due to attrition between enrollment and first dosing).
Respiratory, thoracic and mediastinal disorders Cough or runny nose	11.2% 12/107 • Number of events 14 • Enrollment (<7 days of life) through week 14 study visit (4 months) for serious adverse events; week 6 visit (first vaccine dose) through Week 14 visit + 3 days (end of participation) for all other AEs (2 months) Serious adverse events were recorded from study enrollment (\<7 days of life) but all other adverse events were only recorded starting from the first study intervention (at the week 6 clinic visit), the total numbers of children evaluated for serious adverse events (which is based on study enrollment) differs from those evaluated for adverse events (which is based on the number of children dosed starting at week 6 of life, and is less due to attrition between enrollment and first dosing).	17.0% 18/106 • Number of events 19 • Enrollment (<7 days of life) through week 14 study visit (4 months) for serious adverse events; week 6 visit (first vaccine dose) through Week 14 visit + 3 days (end of participation) for all other AEs (2 months) Serious adverse events were recorded from study enrollment (\<7 days of life) but all other adverse events were only recorded starting from the first study intervention (at the week 6 clinic visit), the total numbers of children evaluated for serious adverse events (which is based on study enrollment) differs from those evaluated for adverse events (which is based on the number of children dosed starting at week 6 of life, and is less due to attrition between enrollment and first dosing).
Gastrointestinal disorders Gastroenteritis (vomiting and/or diarrhea)	17.8% 19/107 • Number of events 21 • Enrollment (<7 days of life) through week 14 study visit (4 months) for serious adverse events; week 6 visit (first vaccine dose) through Week 14 visit + 3 days (end of participation) for all other AEs (2 months) Serious adverse events were recorded from study enrollment (\<7 days of life) but all other adverse events were only recorded starting from the first study intervention (at the week 6 clinic visit), the total numbers of children evaluated for serious adverse events (which is based on study enrollment) differs from those evaluated for adverse events (which is based on the number of children dosed starting at week 6 of life, and is less due to attrition between enrollment and first dosing).	17.0% 18/106 • Number of events 21 • Enrollment (<7 days of life) through week 14 study visit (4 months) for serious adverse events; week 6 visit (first vaccine dose) through Week 14 visit + 3 days (end of participation) for all other AEs (2 months) Serious adverse events were recorded from study enrollment (\<7 days of life) but all other adverse events were only recorded starting from the first study intervention (at the week 6 clinic visit), the total numbers of children evaluated for serious adverse events (which is based on study enrollment) differs from those evaluated for adverse events (which is based on the number of children dosed starting at week 6 of life, and is less due to attrition between enrollment and first dosing).
Infections and infestations Respiratory tract infection	20.6% 22/107 • Number of events 24 • Enrollment (<7 days of life) through week 14 study visit (4 months) for serious adverse events; week 6 visit (first vaccine dose) through Week 14 visit + 3 days (end of participation) for all other AEs (2 months) Serious adverse events were recorded from study enrollment (\<7 days of life) but all other adverse events were only recorded starting from the first study intervention (at the week 6 clinic visit), the total numbers of children evaluated for serious adverse events (which is based on study enrollment) differs from those evaluated for adverse events (which is based on the number of children dosed starting at week 6 of life, and is less due to attrition between enrollment and first dosing).	19.8% 21/106 • Number of events 24 • Enrollment (<7 days of life) through week 14 study visit (4 months) for serious adverse events; week 6 visit (first vaccine dose) through Week 14 visit + 3 days (end of participation) for all other AEs (2 months) Serious adverse events were recorded from study enrollment (\<7 days of life) but all other adverse events were only recorded starting from the first study intervention (at the week 6 clinic visit), the total numbers of children evaluated for serious adverse events (which is based on study enrollment) differs from those evaluated for adverse events (which is based on the number of children dosed starting at week 6 of life, and is less due to attrition between enrollment and first dosing).

Additional Information

Benjamin Lee

The University of Vermont College of Medicine

Phone: 8026567748

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place