Trial Outcomes & Findings for Efficacy, Safety, Reactogenicity & Immunogenicity of the Rotarix Vaccine in Japanese Infants (NCT NCT00480324)
NCT ID: NCT00480324
Last Updated: 2020-01-02
Results Overview
Rotavirus (RV) gastroenteritis (GE) was defined as an episode of any severity GE leading to a medical intervention occurring at least two weeks after dose 2 in which rotavirus other than vaccine strain is identified in a stool sample collected as soon as possible but preferably not later than 7 days after the start of the episode.
COMPLETED
PHASE3
765 participants
From 2 weeks after Dose 2 up to 2 years of age
2020-01-02
Participant Flow
Participant milestones
| Measure |
Rotarix Group
Subjects received 2 oral doses of Rotarix according to a 0, 1 month schedule.
|
Placebo Group
Subjects received 2 oral doses of placebo according to a 0, 1 month schedule.
|
|---|---|---|
|
Overall Study
STARTED
|
508
|
257
|
|
Overall Study
COMPLETED
|
476
|
241
|
|
Overall Study
NOT COMPLETED
|
32
|
16
|
Reasons for withdrawal
| Measure |
Rotarix Group
Subjects received 2 oral doses of Rotarix according to a 0, 1 month schedule.
|
Placebo Group
Subjects received 2 oral doses of placebo according to a 0, 1 month schedule.
|
|---|---|---|
|
Overall Study
Adverse Event
|
1
|
1
|
|
Overall Study
Protocol Violation
|
0
|
1
|
|
Overall Study
Withdrawal by Subject
|
14
|
5
|
|
Overall Study
Lost to Follow-up
|
17
|
8
|
|
Overall Study
Subject's mother pregnant
|
0
|
1
|
Baseline Characteristics
Efficacy, Safety, Reactogenicity & Immunogenicity of the Rotarix Vaccine in Japanese Infants
Baseline characteristics by cohort
| Measure |
Rotarix Group
n=508 Participants
Subjects received 2 oral doses of Rotarix according to a 0, 1 month schedule.
|
Placebo Group
n=257 Participants
Subjects received 2 oral doses of placebo according to a 0, 1 month schedule.
|
Total
n=765 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
7.7 weeks
STANDARD_DEVIATION 1.99 • n=5 Participants
|
7.7 weeks
STANDARD_DEVIATION 2.05 • n=7 Participants
|
7.7 weeks
STANDARD_DEVIATION 2.01 • n=5 Participants
|
|
Sex: Female, Male
Female
|
229 Participants
n=5 Participants
|
134 Participants
n=7 Participants
|
363 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
279 Participants
n=5 Participants
|
123 Participants
n=7 Participants
|
402 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: From 2 weeks after Dose 2 up to 2 years of agePopulation: The analysis was performed on the according-to-protocol (ATP) cohort for efficacy.
Rotavirus (RV) gastroenteritis (GE) was defined as an episode of any severity GE leading to a medical intervention occurring at least two weeks after dose 2 in which rotavirus other than vaccine strain is identified in a stool sample collected as soon as possible but preferably not later than 7 days after the start of the episode.
Outcome measures
| Measure |
Rotarix Group
n=498 Participants
Subjects received 2 oral doses of Rotarix according to a 0, 1 month schedule.
|
Placebo Group
n=250 Participants
Subjects received 2 oral doses of placebo according to a 0, 1 month schedule.
|
|---|---|---|
|
Number of Subjects Reporting Any Rotavirus (RV) Gastroenteritis (GE) Leading to Medical Intervention and Caused by the Circulating Wild-type RV Strains
|
14 subjects
|
34 subjects
|
SECONDARY outcome
Timeframe: From 2 weeks after Dose 2 up to 2 years of agePopulation: The analysis was performed on the according-to-protocol (ATP) cohort for efficacy.
A subject was considered as reporting severe rotavirus gastroenteritis when the subject scored 11 or more on a 20-point scoring system (Vesikari scoring system).
Outcome measures
| Measure |
Rotarix Group
n=498 Participants
Subjects received 2 oral doses of Rotarix according to a 0, 1 month schedule.
|
Placebo Group
n=250 Participants
Subjects received 2 oral doses of placebo according to a 0, 1 month schedule.
|
|---|---|---|
|
Number of Subjects Reporting Severe Rotavirus (RV) Gastroenteritis (GE) Leading to Medical Intervention and Caused by the Circulating Wild-type RV Strains
|
2 subjects
|
12 subjects
|
SECONDARY outcome
Timeframe: From 2 weeks after Dose 2 up to 2 years of agePopulation: The analysis was performed on the according-to-protocol (ATP) cohort for efficacy.
Rotavirus (RV) gastroenteritis (GE) was defined as an episode of any severity GE leading to a medical intervention occurring at least two weeks after dose 2 in which rotavirus other than vaccine strain is identified in a stool sample collected as soon as possible but preferably not later than 7 days after the start of the episode. Severe RV GE was defined as an episode of rotavirus gastroenteritis with score ≥ 11 on a 20-point scoring system (Vesikari scoring system).
Outcome measures
| Measure |
Rotarix Group
n=498 Participants
Subjects received 2 oral doses of Rotarix according to a 0, 1 month schedule.
|
Placebo Group
n=250 Participants
Subjects received 2 oral doses of placebo according to a 0, 1 month schedule.
|
|---|---|---|
|
Number of Subjects Reporting Any Rotavirus (RV) Gastroenteritis (GE) and Severe RV GE Leading to Medical Intervention and Caused by the Circulating Wild-type RV Strains of G1 Type
Any RV GE
|
4 subjects
|
13 subjects
|
|
Number of Subjects Reporting Any Rotavirus (RV) Gastroenteritis (GE) and Severe RV GE Leading to Medical Intervention and Caused by the Circulating Wild-type RV Strains of G1 Type
Severe RV GE
|
1 subjects
|
6 subjects
|
SECONDARY outcome
Timeframe: From 2 weeks after Dose 2 up to 2 years of agePopulation: The analysis was performed on the according-to-protocol (ATP) cohort for efficacy.
Rotavirus (RV) gastroenteritis (GE) was defined as an episode of any severity GE leading to a medical intervention occurring at least two weeks after dose 2 in which rotavirus other than vaccine strain is identified in a stool sample collected as soon as possible but preferably not later than 7 days after the start of the episode. Severe rotavirus gastroenteritis was defined as an episode of rotavirus gastroenteritis with score ≥ 11 on a 20-point scoring system (Vesikari scoring system).
Outcome measures
| Measure |
Rotarix Group
n=498 Participants
Subjects received 2 oral doses of Rotarix according to a 0, 1 month schedule.
|
Placebo Group
n=250 Participants
Subjects received 2 oral doses of placebo according to a 0, 1 month schedule.
|
|---|---|---|
|
Number of Subjects Reporting Any Rotavirus (RV) Gastroenteritis (GE) and Severe RV GE Leading to Medical Intervention and Caused by the Circulating Wild-type RV Strains of Non-G1 Types
Any RV GE
|
10 subjects
|
21 subjects
|
|
Number of Subjects Reporting Any Rotavirus (RV) Gastroenteritis (GE) and Severe RV GE Leading to Medical Intervention and Caused by the Circulating Wild-type RV Strains of Non-G1 Types
Severe RV GE
|
1 subjects
|
6 subjects
|
SECONDARY outcome
Timeframe: From 2 weeks after Dose 2 up to 2 years of agePopulation: The analysis was performed on the according-to-protocol (ATP) cohort for efficacy.
Rotavirus (RV) gastroenteritis (GE) was defined as an episode of any severity GE leading to a medical intervention occurring at least two weeks after dose 2 in which rotavirus other than vaccine strain is identified in a stool sample collected as soon as possible but preferably not later than 7 days after the start of the episode.
Outcome measures
| Measure |
Rotarix Group
n=498 Participants
Subjects received 2 oral doses of Rotarix according to a 0, 1 month schedule.
|
Placebo Group
n=250 Participants
Subjects received 2 oral doses of placebo according to a 0, 1 month schedule.
|
|---|---|---|
|
Number of Subjects Hospitalized Due to Rotavirus (RV) Gastroenteritis (GE) Caused by the Circulating Wild-type RV Strains
|
1 subjects
|
2 subjects
|
SECONDARY outcome
Timeframe: From Dose 1 up to 2 years of agePopulation: The analysis was performed on the Total Vaccinated cohort.
Rotavirus (RV) gastroenteritis (GE) was defined as an episode of any severity GE leading to a medical intervention occurring at least two weeks after dose 2 in which rotavirus other than vaccine strain is identified in a stool sample collected as soon as possible but preferably not later than 7 days after the start of the episode. Severe rotavirus gastroenteritis was defined as an episode of rotavirus gastroenteritis with score ≥ 11 on a 20-point scoring system (Vesikari scoring system).
Outcome measures
| Measure |
Rotarix Group
n=508 Participants
Subjects received 2 oral doses of Rotarix according to a 0, 1 month schedule.
|
Placebo Group
n=257 Participants
Subjects received 2 oral doses of placebo according to a 0, 1 month schedule.
|
|---|---|---|
|
Number of Subjects Reporting Any Rotavirus (RV) Gatroenteritis (GE) and Severe RV GE Leading to Medical Intervention and Caused by the Circulating Wild-type RV Strains
Any RV GE
|
14 subjects
|
36 subjects
|
|
Number of Subjects Reporting Any Rotavirus (RV) Gatroenteritis (GE) and Severe RV GE Leading to Medical Intervention and Caused by the Circulating Wild-type RV Strains
Severe RV GE
|
2 subjects
|
13 subjects
|
SECONDARY outcome
Timeframe: 2 months after Dose 2Population: The analysis was performed on the according-to-protocol (ATP) cohort for immunogenicity.
Anti-rotavirus immunoglobulin A antibody concentrations are given as geometric mean concentrations (GMCs). Arbitrary 'zero' values were set in the Placebo Group since the GMC was below the assay cut-off value (20 U/mL).
Outcome measures
| Measure |
Rotarix Group
n=34 Participants
Subjects received 2 oral doses of Rotarix according to a 0, 1 month schedule.
|
Placebo Group
n=20 Participants
Subjects received 2 oral doses of placebo according to a 0, 1 month schedule.
|
|---|---|---|
|
Serum Anti-rotavirus Immunoglobulin A (IgA) Antibody Concentration
|
217.0 Units per milliliter (U/mL)
Interval 109.9 to 428.6
|
0 Units per milliliter (U/mL)
Interval 0.0 to 0.0
|
SECONDARY outcome
Timeframe: 2 months after Dose 2Population: The analysis was performed on the according-to-protocol (ATP) cohort for immunogenicity.
Seroconversion was defined as the appearance of anti-rotavirus immunoglobulin A antibody concentration ≥ 20 units (U)/milliliter (mL) in subjects initially (i.e. prior to the first dose of rotarix) seronegative.
Outcome measures
| Measure |
Rotarix Group
n=34 Participants
Subjects received 2 oral doses of Rotarix according to a 0, 1 month schedule.
|
Placebo Group
n=20 Participants
Subjects received 2 oral doses of placebo according to a 0, 1 month schedule.
|
|---|---|---|
|
Number of Subjects Seroconverted for Anti-rotavirus Immunoglobulin A (IgA) Antibodies
|
29 subjects
|
1 subjects
|
SECONDARY outcome
Timeframe: During the 8-day follow-up period after each dosePopulation: The analysis was performed on the Total Vaccinated cohort.
Solicited symptoms assessed include cough, diarrhoea, fever, irritability, loss of appetite and vomiting.
Outcome measures
| Measure |
Rotarix Group
n=508 Participants
Subjects received 2 oral doses of Rotarix according to a 0, 1 month schedule.
|
Placebo Group
n=257 Participants
Subjects received 2 oral doses of placebo according to a 0, 1 month schedule.
|
|---|---|---|
|
Number of Subjects Reporting Solicited Symptoms
Cough
|
184 subjects
|
92 subjects
|
|
Number of Subjects Reporting Solicited Symptoms
Diarrhoea
|
43 subjects
|
14 subjects
|
|
Number of Subjects Reporting Solicited Symptoms
Fever
|
62 subjects
|
22 subjects
|
|
Number of Subjects Reporting Solicited Symptoms
Irritability
|
261 subjects
|
125 subjects
|
|
Number of Subjects Reporting Solicited Symptoms
Loss of appetite
|
81 subjects
|
33 subjects
|
|
Number of Subjects Reporting Solicited Symptoms
Vomiting
|
74 subjects
|
36 subjects
|
SECONDARY outcome
Timeframe: During the 31-day follow-up period after each dosePopulation: The analysis was performed on the Total Vaccinated cohort.
Unsolicited adverse event (AE) was defined as any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Outcome measures
| Measure |
Rotarix Group
n=508 Participants
Subjects received 2 oral doses of Rotarix according to a 0, 1 month schedule.
|
Placebo Group
n=257 Participants
Subjects received 2 oral doses of placebo according to a 0, 1 month schedule.
|
|---|---|---|
|
Number of Subjects Reporting Unsolicited Adverse Events (AEs)
|
279 subjects
|
144 subjects
|
SECONDARY outcome
Timeframe: Up to 2 years of agePopulation: The analysis was performed on the Total Vaccinated cohort.
Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subject.
Outcome measures
| Measure |
Rotarix Group
n=508 Participants
Subjects received 2 oral doses of Rotarix according to a 0, 1 month schedule.
|
Placebo Group
n=257 Participants
Subjects received 2 oral doses of placebo according to a 0, 1 month schedule.
|
|---|---|---|
|
Number of Subjects Reporting Serious Adverse Events (SAEs)
|
72 subjects
|
44 subjects
|
Adverse Events
Rotarix Group
Placebo Group
Serious adverse events
| Measure |
Rotarix Group
n=508 participants at risk
Subjects received 2 oral doses of Rotarix according to a 0, 1 month schedule.
|
Placebo Group
n=257 participants at risk
Subjects received 2 oral doses of placebo according to a 0, 1 month schedule.
|
|---|---|---|
|
Infections and infestations
Pneumonia
|
2.4%
12/508
|
1.6%
4/257
|
|
Infections and infestations
Bronchitis
|
2.8%
14/508
|
0.00%
0/257
|
|
Infections and infestations
Gastroenteritis
|
2.2%
11/508
|
0.78%
2/257
|
|
Respiratory, thoracic and mediastinal disorders
Asthma
|
0.98%
5/508
|
1.2%
3/257
|
|
Infections and infestations
Pharyngitis
|
0.98%
5/508
|
1.2%
3/257
|
|
Infections and infestations
Respiratory syncytial virus bronchiolitis
|
1.2%
6/508
|
0.78%
2/257
|
|
Infections and infestations
Respiratory syncytial virus infection
|
0.98%
5/508
|
1.2%
3/257
|
|
Infections and infestations
Exanthema subitum
|
0.59%
3/508
|
0.78%
2/257
|
|
Nervous system disorders
Febrile convulsion
|
0.79%
4/508
|
0.39%
1/257
|
|
Infections and infestations
Upper respiratory tract infection
|
0.79%
4/508
|
0.39%
1/257
|
|
Infections and infestations
Bronchopneumonia
|
0.39%
2/508
|
0.78%
2/257
|
|
Metabolism and nutrition disorders
Dehydration
|
0.59%
3/508
|
0.39%
1/257
|
|
Infections and infestations
Otitis media acute
|
0.20%
1/508
|
1.2%
3/257
|
|
General disorders
Pyrexia
|
0.59%
3/508
|
0.39%
1/257
|
|
Infections and infestations
Urinary tract infection
|
0.39%
2/508
|
0.78%
2/257
|
|
Nervous system disorders
Convulsion
|
0.20%
1/508
|
0.78%
2/257
|
|
Gastrointestinal disorders
Enterocolitis
|
0.39%
2/508
|
0.39%
1/257
|
|
Infections and infestations
Gastroenteritis rotavirus
|
0.20%
1/508
|
0.78%
2/257
|
|
Gastrointestinal disorders
Gastrointestinal disorder
|
0.20%
1/508
|
0.78%
2/257
|
|
Infections and infestations
Influenza
|
0.20%
1/508
|
0.78%
2/257
|
|
Blood and lymphatic system disorders
Iron deficiency anaemia
|
0.20%
1/508
|
0.78%
2/257
|
|
Infections and infestations
Acute tonsilitis
|
0.20%
1/508
|
0.39%
1/257
|
|
Infections and infestations
Adenovirus infection
|
0.00%
0/508
|
0.78%
2/257
|
|
Infections and infestations
Cellulitis
|
0.00%
0/508
|
0.78%
2/257
|
|
Infections and infestations
Enterocolitis viral
|
0.39%
2/508
|
0.00%
0/257
|
|
Infections and infestations
Gastroenteritis viral
|
0.20%
1/508
|
0.39%
1/257
|
|
Gastrointestinal disorders
Haematochezia
|
0.39%
2/508
|
0.00%
0/257
|
|
Hepatobiliary disorders
Hepatic function abnormal
|
0.00%
0/508
|
0.78%
2/257
|
|
Vascular disorders
Kawasaki's disease
|
0.20%
1/508
|
0.39%
1/257
|
|
Infections and infestations
Laryngitis
|
0.39%
2/508
|
0.00%
0/257
|
|
Respiratory, thoracic and mediastinal disorders
Adenoidal hypertrophy
|
0.00%
0/508
|
0.39%
1/257
|
|
Blood and lymphatic system disorders
Aplasia pure red cell
|
0.00%
0/508
|
0.39%
1/257
|
|
Musculoskeletal and connective tissue disorders
Arthritis
|
0.00%
0/508
|
0.39%
1/257
|
|
Infections and infestations
Bacteraemia
|
0.00%
0/508
|
0.39%
1/257
|
|
Infections and infestations
Bacterial infection
|
0.20%
1/508
|
0.00%
0/257
|
|
Psychiatric disorders
Breath holding
|
0.00%
0/508
|
0.39%
1/257
|
|
Gastrointestinal disorders
Colitis
|
0.20%
1/508
|
0.00%
0/257
|
|
Eye disorders
Conjunctivitis
|
0.20%
1/508
|
0.00%
0/257
|
|
Injury, poisoning and procedural complications
Contusion
|
0.00%
0/508
|
0.39%
1/257
|
|
Infections and infestations
Croup infectious
|
0.20%
1/508
|
0.00%
0/257
|
|
Congenital, familial and genetic disorders
Cryptorchism
|
0.00%
0/508
|
0.39%
1/257
|
|
Gastrointestinal disorders
Diarrhoea
|
0.20%
1/508
|
0.00%
0/257
|
|
Gastrointestinal disorders
Enteritis
|
0.20%
1/508
|
0.00%
0/257
|
|
Infections and infestations
Erythema infectiosum
|
0.00%
0/508
|
0.39%
1/257
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Fibroma
|
0.20%
1/508
|
0.00%
0/257
|
|
Hepatobiliary disorders
Hepatic failure
|
0.20%
1/508
|
0.00%
0/257
|
|
Gastrointestinal disorders
Inguinal hernia
|
0.20%
1/508
|
0.00%
0/257
|
|
Infections and infestations
Nasopharyngitis
|
0.00%
0/508
|
0.39%
1/257
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasm
|
0.20%
1/508
|
0.00%
0/257
|
|
Infections and infestations
Otitis media
|
0.20%
1/508
|
0.00%
0/257
|
|
Infections and infestations
Pertussis
|
0.00%
0/508
|
0.39%
1/257
|
|
Infections and infestations
Pneumonia respiratory syncytial viral
|
0.20%
1/508
|
0.00%
0/257
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
0.20%
1/508
|
0.00%
0/257
|
|
Infections and infestations
Sinusitis
|
0.00%
0/508
|
0.39%
1/257
|
|
Injury, poisoning and procedural complications
Skull fracture
|
0.00%
0/508
|
0.39%
1/257
|
|
Nervous system disorders
Status epilepticus
|
0.00%
0/508
|
0.39%
1/257
|
|
Nervous system disorders
Subarachnoid haemorrhage
|
0.00%
0/508
|
0.39%
1/257
|
|
Infections and infestations
Subcutaneous abscess
|
0.00%
0/508
|
0.39%
1/257
|
|
Injury, poisoning and procedural complications
Subdural haematoma
|
0.20%
1/508
|
0.00%
0/257
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Teratoma
|
0.20%
1/508
|
0.00%
0/257
|
|
Infections and infestations
Tonsillitis
|
0.00%
0/508
|
0.39%
1/257
|
|
Respiratory, thoracic and mediastinal disorders
Upper respiratory tract inflammation
|
0.00%
0/508
|
0.39%
1/257
|
|
Metabolism and nutrition disorders
Weight gain poor
|
0.00%
0/508
|
0.39%
1/257
|
Other adverse events
| Measure |
Rotarix Group
n=508 participants at risk
Subjects received 2 oral doses of Rotarix according to a 0, 1 month schedule.
|
Placebo Group
n=257 participants at risk
Subjects received 2 oral doses of placebo according to a 0, 1 month schedule.
|
|---|---|---|
|
Skin and subcutaneous tissue disorders
Eczema
|
14.2%
72/508
|
11.3%
29/257
|
|
Infections and infestations
Upper respiratory tract infection
|
9.8%
50/508
|
9.7%
25/257
|
|
Respiratory, thoracic and mediastinal disorders
Upper respiratory tract inflammation
|
6.5%
33/508
|
6.2%
16/257
|
|
Infections and infestations
Nasopharyngitis
|
6.1%
31/508
|
5.1%
13/257
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
3.7%
19/508
|
8.2%
21/257
|
|
General disorders
Cough
|
36.2%
184/508
|
35.8%
92/257
|
|
General disorders
Diarrhoea
|
8.5%
43/508
|
5.4%
14/257
|
|
General disorders
Fever
|
12.2%
62/508
|
8.6%
22/257
|
|
General disorders
Irritability
|
51.4%
261/508
|
48.6%
125/257
|
|
General disorders
Loss of appetite
|
15.9%
81/508
|
12.8%
33/257
|
|
General disorders
Vomiting
|
14.6%
74/508
|
14.0%
36/257
|
Additional Information
GSK Response Center
GlaxoSmithKline
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