Trial Outcomes & Findings for A Study to Explore the Existence of Horizontal Transmission of the RIX4414 Vaccine Strain Between Twins Within a Family. (NCT NCT00396630)

NCT ID: NCT00396630

Last Updated: 2018-02-06

Results Overview

Number of subjects in the Placebo Group with rotavirus vaccine strain in at least one stool sample.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 200 participants
• Primary outcome timeframe: On the day of each vaccine/placebo dose, then three times weekly for 6 consecutive weeks starting after each vaccine/placebo dose and on the day of Visit 3.
• Results posted on: 2018-02-06

Participant Flow

Within each pair of twins enrolled in the study, one subject was assigned to the Rotarix Group and one to the Placebo Group.

Participant milestones

Measure	Rotarix Group All subjects received 2 oral doses of Rotarix vaccine at Day 0 (Visit 1) and Week 7 (Visit 2). Subjects aged less than 6 months at Visit 3 received one complimentary Rotarix vaccine dose at Week 13 (Visit 3).	Placebo Group All subjects received 2 oral doses of placebo at Day 0 (Visit 1) and Week 7 (Visit 2). Subjects aged less than 6 months at Visit 3 received one complimentary Rotarix vaccine dose at Week 13 (Visit 3).
Overall Study STARTED	100	100
Overall Study COMPLETED	95	95
Overall Study NOT COMPLETED	5	5

Reasons for withdrawal

Measure	Rotarix Group All subjects received 2 oral doses of Rotarix vaccine at Day 0 (Visit 1) and Week 7 (Visit 2). Subjects aged less than 6 months at Visit 3 received one complimentary Rotarix vaccine dose at Week 13 (Visit 3).	Placebo Group All subjects received 2 oral doses of placebo at Day 0 (Visit 1) and Week 7 (Visit 2). Subjects aged less than 6 months at Visit 3 received one complimentary Rotarix vaccine dose at Week 13 (Visit 3).
Overall Study Lost to Follow-up	1	1
Overall Study Withdrawal by Subject	1	1
Overall Study Not vaccinated at Visit 3	3	3

Baseline Characteristics

A Study to Explore the Existence of Horizontal Transmission of the RIX4414 Vaccine Strain Between Twins Within a Family.

Baseline characteristics by cohort

Measure	Rotarix Group n=100 Participants All subjects received 2 oral doses of Rotarix vaccine at Day 0 (Visit 1) and Week 7 (Visit 2). Subjects aged less than 6 months at Visit 3 received one complimentary Rotarix vaccine dose at Week 13 (Visit 3).	Placebo Group n=100 Participants All subjects received 2 oral doses of placebo at Day 0 (Visit 1) and Week 7 (Visit 2). Subjects aged less than 6 months at Visit 3 received one complimentary Rotarix vaccine dose at Week 13 (Visit 3).	Total n=200 Participants Total of all reporting groups
Age, Continuous	8.2 Weeks STANDARD_DEVIATION 1.80 • n=5 Participants	8.2 Weeks STANDARD_DEVIATION 1.80 • n=7 Participants	8.2 Weeks STANDARD_DEVIATION 1.80 • n=5 Participants
Sex: Female, Male Female	56 Participants n=5 Participants	49 Participants n=7 Participants	105 Participants n=5 Participants
Sex: Female, Male Male	44 Participants n=5 Participants	51 Participants n=7 Participants	95 Participants n=5 Participants

PRIMARY outcome

Timeframe: On the day of each vaccine/placebo dose, then three times weekly for 6 consecutive weeks starting after each vaccine/placebo dose and on the day of Visit 3.

Population: The analyses were performed on the According-To-Protocol (ATP) cohort for immunogenicity.

Number of subjects in the Placebo Group with rotavirus vaccine strain in at least one stool sample.

Outcome measures

Measure	Placebo Group n=80 Participants All subjects received 2 oral doses of placebo at Day 0 (Visit 1) and Week 7 (Visit 2). Subjects aged less than 6 months at Visit 3 received one complimentary Rotarix vaccine dose at Week 13 (Visit 3).	Placebo Group All subjects received 2 oral doses of placebo at Day 0 (Visit 1) and Week 7 (Visit 2). Subjects aged less than 6 months at Visit 3 received one complimentary Rotarix vaccine dose at Week 13 (Visit 3).
Presence of Rotavirus Vaccine Strain in Any Stool Sample From Twin Receiving Placebo.	15 subjects	—

SECONDARY outcome

Timeframe: From Day 0 up to Week 13.

Population: The analysis was performed on the According To Protocol analysis for immunogenicity, on the twins whose placebo recipient had at least one stool sample positive for the rotavirus strain.

Duration of shedding in the Placebo Group= number of days between first and last stool sample positive (+) for rotavirus (RV) antigen and in the Rotarix Group= number of days between the day of vaccination and the date of last stool sample + for RV antigen.

Outcome measures

Measure	Placebo Group n=15 Participants All subjects received 2 oral doses of placebo at Day 0 (Visit 1) and Week 7 (Visit 2). Subjects aged less than 6 months at Visit 3 received one complimentary Rotarix vaccine dose at Week 13 (Visit 3).	Placebo Group n=15 Participants All subjects received 2 oral doses of placebo at Day 0 (Visit 1) and Week 7 (Visit 2). Subjects aged less than 6 months at Visit 3 received one complimentary Rotarix vaccine dose at Week 13 (Visit 3).
Duration of Human Rotavirus (HRV) Shedding Per Study Group. After Dose 1 (n=11, 9)	17 Number of days Interval 11.0 to 19.0	7 Number of days Interval 3.0 to 13.0
Duration of Human Rotavirus (HRV) Shedding Per Study Group. After Dose 2 (n=9, 7)	13 Number of days Interval 5.0 to 17.0	1 Number of days Interval 1.0 to 1.0

SECONDARY outcome

Timeframe: During the entire study period (up to Visit 4, Week 17).

Population: The analysis was performed on the According To Protocol analysis for immunogenicity, on the twins who received placebo and those who received Rotarix vaccine, in case of transmission.

Dissimilar amino acid substitutions in the HRV vaccine strain isolated from the twin receiving placebo, when compared to the genetic variation of HRV vaccine strain isolated from the Rotarix vaccine recipients, were counted as genetic variation differences.

Outcome measures

Measure	Placebo Group n=15 Participants All subjects received 2 oral doses of placebo at Day 0 (Visit 1) and Week 7 (Visit 2). Subjects aged less than 6 months at Visit 3 received one complimentary Rotarix vaccine dose at Week 13 (Visit 3).	Placebo Group n=15 Participants All subjects received 2 oral doses of placebo at Day 0 (Visit 1) and Week 7 (Visit 2). Subjects aged less than 6 months at Visit 3 received one complimentary Rotarix vaccine dose at Week 13 (Visit 3).
Number of Genetic Variation Differences Detected by Sequencing of Genomic Mutations in the HRV Vaccine Strain After Transmission.	0 Genetic variation difference	0 Genetic variation difference

SECONDARY outcome

Timeframe: During the entire study period (up to Visit 4, Week 17).

Population: The analysis was performed on the According To Protocol analysis for immunogenicity, on the twins who received placebo in case of transmission.

Number of subjects in the Placebo Group with live virus identified in at least one stool sample in case of transmission.

Outcome measures

Measure	Placebo Group n=15 Participants All subjects received 2 oral doses of placebo at Day 0 (Visit 1) and Week 7 (Visit 2). Subjects aged less than 6 months at Visit 3 received one complimentary Rotarix vaccine dose at Week 13 (Visit 3).	Placebo Group All subjects received 2 oral doses of placebo at Day 0 (Visit 1) and Week 7 (Visit 2). Subjects aged less than 6 months at Visit 3 received one complimentary Rotarix vaccine dose at Week 13 (Visit 3).
Live Viral Vaccine Load in the Stool of the Twin Receiving Placebo in Case of Transmission.	3 Subjects	—

SECONDARY outcome

Timeframe: At Visit 3 (Week 13).

Population: The analyses were performed on the According-To-Protocol (ATP) cohort for immunogenicity.

Number of initially seronegative subjects with anti-rotavirus IgA antibody concentration ≥ 20 Units/milliliter (U/mL), 1 month after the second dose.

Outcome measures

Measure	Placebo Group n=80 Participants All subjects received 2 oral doses of placebo at Day 0 (Visit 1) and Week 7 (Visit 2). Subjects aged less than 6 months at Visit 3 received one complimentary Rotarix vaccine dose at Week 13 (Visit 3).	Placebo Group n=80 Participants All subjects received 2 oral doses of placebo at Day 0 (Visit 1) and Week 7 (Visit 2). Subjects aged less than 6 months at Visit 3 received one complimentary Rotarix vaccine dose at Week 13 (Visit 3).
Anti-rotavirus Immunoglobulin A (IgA) Antibody Seroconversion.	50 subjects	17 subjects

SECONDARY outcome

Timeframe: At Visit 3 (Week 13).

Population: The analyses were performed on the According-To-Protocol (ATP) cohort for immunogenicity.

Anti-rotavirus IgA antibody concentrations are given as geometric mean concentrations (GMC) with 95% Confidence Intervals.

Outcome measures

Measure	Placebo Group n=80 Participants All subjects received 2 oral doses of placebo at Day 0 (Visit 1) and Week 7 (Visit 2). Subjects aged less than 6 months at Visit 3 received one complimentary Rotarix vaccine dose at Week 13 (Visit 3).	Placebo Group n=80 Participants All subjects received 2 oral doses of placebo at Day 0 (Visit 1) and Week 7 (Visit 2). Subjects aged less than 6 months at Visit 3 received one complimentary Rotarix vaccine dose at Week 13 (Visit 3).
Anti-rotavirus IgA Antibody Concentration.	78.6 U/mL Interval 50.6 to 122.2	20.5 U/mL Interval 14.5 to 28.9

SECONDARY outcome

Timeframe: Until Visit 4 (Week 17) for GE and until Visit 3 (Week 13) for RV GE.

Population: The analyses were performed on the Total Vaccinated Cohort

GE episodes were defined as diarrhea (passage of three or more looser than normal stools within a day) with or without vomiting.

RV GE episodes were defined as GE episodes for which the stool sample temporally closest to the onset day of the GE episode was positive for rotavirus by Enzyme Linked Immunosorbent Assay (ELISA).

Outcome measures

Measure	Placebo Group n=100 Participants All subjects received 2 oral doses of placebo at Day 0 (Visit 1) and Week 7 (Visit 2). Subjects aged less than 6 months at Visit 3 received one complimentary Rotarix vaccine dose at Week 13 (Visit 3).	Placebo Group n=100 Participants All subjects received 2 oral doses of placebo at Day 0 (Visit 1) and Week 7 (Visit 2). Subjects aged less than 6 months at Visit 3 received one complimentary Rotarix vaccine dose at Week 13 (Visit 3).
Number of Subjects With Gastroenteritis (GE) and Rotavirus Gastroenteritis (RV GE) Episodes. GE episodes	32 subjects	31 subjects
Number of Subjects With Gastroenteritis (GE) and Rotavirus Gastroenteritis (RV GE) Episodes. RV GE episodes	10 subjects	6 subjects

SECONDARY outcome

Timeframe: Within 31 days after any doses.

Population: The analyses were performed on the Total Vaccinated Cohort

An AE is any untoward medical occurrence in a clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.

Outcome measures

Measure	Placebo Group n=100 Participants All subjects received 2 oral doses of placebo at Day 0 (Visit 1) and Week 7 (Visit 2). Subjects aged less than 6 months at Visit 3 received one complimentary Rotarix vaccine dose at Week 13 (Visit 3).	Placebo Group n=100 Participants All subjects received 2 oral doses of placebo at Day 0 (Visit 1) and Week 7 (Visit 2). Subjects aged less than 6 months at Visit 3 received one complimentary Rotarix vaccine dose at Week 13 (Visit 3).
Number of Subjects Reporting Unsolicited Adverse Events (AEs).	69 subjects	71 subjects

SECONDARY outcome

Timeframe: Up to Visit 4.

Population: The analyses were performed on the Total Vaccinated Cohort

A serious adverse event (SAE) is any untoward medical occurrence that:

results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study subject, or may evolve into one of the outcomes listed above.

Outcome measures

Measure	Placebo Group n=100 Participants All subjects received 2 oral doses of placebo at Day 0 (Visit 1) and Week 7 (Visit 2). Subjects aged less than 6 months at Visit 3 received one complimentary Rotarix vaccine dose at Week 13 (Visit 3).	Placebo Group n=100 Participants All subjects received 2 oral doses of placebo at Day 0 (Visit 1) and Week 7 (Visit 2). Subjects aged less than 6 months at Visit 3 received one complimentary Rotarix vaccine dose at Week 13 (Visit 3).
Number of Subjects Reporting Any Serious Adverse Events (SAEs).	5 subjects	6 subjects

Adverse Events

Rotarix Group

Serious events: 5 serious events

Other events: 69 other events

Deaths: 0 deaths

Placebo Group

Serious events: 6 serious events

Other events: 71 other events

Deaths: 0 deaths

Serious adverse events

Measure	Rotarix Group n=100 participants at risk All subjects received 2 oral doses of Rotarix vaccine at Day 0 (Visit 1) and Week 7 (Visit 2). Subjects aged less than 6 months at Visit 3 received one complimentary Rotarix vaccine dose at Week 13 (Visit 3).	Placebo Group n=100 participants at risk All subjects received 2 oral doses of placebo at Day 0 (Visit 1) and Week 7 (Visit 2). Subjects aged less than 6 months at Visit 3 received one complimentary Rotarix vaccine dose at Week 13 (Visit 3).
Infections and infestations Bronchiolitis	3.0% 3/100	3.0% 3/100
Infections and infestations Gastroenteritis	2.0% 2/100	1.0% 1/100
Infections and infestations Bacterial sepsis	1.0% 1/100	0.00% 0/100
Infections and infestations Bronchitis	0.00% 0/100	1.0% 1/100
Infections and infestations Pneumonia	0.00% 0/100	1.0% 1/100

Other adverse events

Measure	Rotarix Group n=100 participants at risk All subjects received 2 oral doses of Rotarix vaccine at Day 0 (Visit 1) and Week 7 (Visit 2). Subjects aged less than 6 months at Visit 3 received one complimentary Rotarix vaccine dose at Week 13 (Visit 3).	Placebo Group n=100 participants at risk All subjects received 2 oral doses of placebo at Day 0 (Visit 1) and Week 7 (Visit 2). Subjects aged less than 6 months at Visit 3 received one complimentary Rotarix vaccine dose at Week 13 (Visit 3).
Infections and infestations Nasopharyngitis	49.0% 49/100	49.0% 49/100
General disorders Pyrexia	32.0% 32/100	32.0% 32/100
General disorders Irritability	4.0% 4/100	5.0% 5/100

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Results disclosure agreements

• Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
• Publication restrictions are in place

Restriction type: OTHER