Evaluation of Reactogenicity and Safety of GSK Biologicals' Rotarix (Human Rotavirus Vaccine) in Infants

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00750893
• Collaborator: (none)
• Enrollment: 3,111
• Location: 1
• Actual Duration (Months): 57.4
• Patients Per Site Per Month: 54.2

Study Details

Study Description

Brief Summary

This protocol posting deals with objectives and outcome measures of the primary phase at one month post-Dose 2. This Post Marketing Surveillance (PMS) will collect safety data on the use of human rotavirus vaccine in at least 3000 evaluable infants in Korea. This study involves male or female infants from the age of 6 weeks at the time of the first vaccination. The vaccination course must be completed by the age of 24 weeks.

Condition or Disease	Intervention/Treatment	Phase
Infections, Rotavirus	Biological: Rotarix or Rotarix liquid formulation

Detailed Description

The protocol posting has been amended to reflect the two new vaccine presentations that have been launched in Korea. The current PMS will thus collect safety information from subjects who have received either Rotarix or Rotarix liquid formulation (oral suspension or prefilled syringe) in the course of their routine clinical practice according to the prescribing information in Korea.

Study Design

• Study Type: Observational
• Actual Enrollment: 3111 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Safety of GlaxoSmithKline Biologicals' Oral Live Attenuated Human Rotavirus Vaccine, Rotarix or Rotarix Liquid Formulation (Oral Suspension or Prefilled Syringe) When Administered According to the Prescribing Information in Korea
• Actual Study Start Date: Sep 2, 2008
• Actual Primary Completion Date: Jun 15, 2013
• Actual Study Completion Date: Jun 15, 2013

Arms and Interventions

Arm	Intervention/Treatment
Rotarix Group Subjects who received 2 oral doses of Rotarix. The first dose was administered before the age of 6 weeks and the second one at least 4 weeks after, preferably before the age of 16 weeks. The 2 doses had to be given before 24 weeks of age.	Biological: Rotarix or Rotarix liquid formulation; GSK Biologicals' oral live attenuated human rotavirus (HRV) vaccine (oral suspension or prefilled syringe).

Outcome Measures

Primary Outcome Measures

1. Number of Subjects Reporting Solicited General Symptoms [During the 8-day follow-up period after each vaccine dose for Year 1 & Year 2 study period]

   Solicited general symptoms assessed include cough, diarrhoea, irritability, loss of appetite, temperature and vomiting.

2. Number of Subjects Reporting Unsolicited Adverse Events (AEs) During the 31-day Follow-up Period After Each Vaccine Dose for Year 1 & Year 2 Study Period [During the 31-day follow-up period after each vaccine dose for Year 1 & Year 2 study period]

   Unsolicited AE covers any AE reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms.

3. Number of Subjects Reporting Unsolicited Adverse Events (AEs) During the 31-day Follow-up Period After Each Vaccine Dose for Year 3 & Year 4 Study Period [During the 31-day follow-up period after each vaccine dose for Year 3 & Year 4 study period]

   Unsolicited AE covers any AE reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms.

4. Number of Subjects Reporting Unsolicited Adverse Events (AEs) During the 31-day Follow-up Period After Each Vaccine Dose for Year 5 Study Period [During the 31 day follow-up period after each vaccine dose for Year 5 study period]

   Unsolicited AE covers any AE reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms.

5. Number of Subjects Reporting Unsolicited Adverse Events (AEs) During the 31-day Follow-up Period After Each Vaccine Dose for Year 1 to Year 6 Study Period [During the 31-day follow-up period after each vaccine dose for Year 1 to Year 6 study period]

   Unsolicited AE covers any AE reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms.

6. Number of Subjects Reporting Serious Adverse Events (SAEs) During the Post-marketing Study Period for Year 1 & Year 2 Study Period [During the post-marketing study period for Year 1 & Year 2 study period]

   SAEs assessed include medical occurrences that resulted in death, were life-threatening, required hospitalization or prolongation of hospitalization, resulted in disability/incapacity or were a congenital anomaly/birth defect in the offspring of a study subject.

7. Number of Subjects Reporting Serious Adverse Events (SAEs) During the Post-marketing Study Period for Year 3 & Year 4 Study Period [During the post-marketing study period for Year 3 & Year 4 study period]

   SAEs assessed include medical occurrences that resulted in death, were life-threatening, required hospitalization or prolongation of hospitalization, resulted in disability/incapacity or were a congenital anomaly/birth defect in the offspring of a study subject.

8. Number of Subjects Reporting Serious Adverse Events (SAEs) During the Post-marketing Study Period for Year 5 Study Period [During the post-marketing study period for Year 5 study period]

   SAEs assessed include medical occurrences that resulted in death, were life-threatening, required hospitalization or prolongation of hospitalization, resulted in disability/incapacity or were a congenital anomaly/birth defect in the offspring of a study subject.

9. Number of Subjects Reporting Serious Adverse Events (SAEs) During the Post-marketing Study Period for Year 1 to Year 6 Study Period [During the post-marketing study period for Year 1 to Year 6 study period]

   SAEs assessed include medical occurrences that resulted in death, were life-threatening, required hospitalization or prolongation of hospitalization, resulted in disability/incapacity or were a congenital anomaly/birth defect in the offspring of a study subject.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 6 Weeks to 24 Weeks
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Infants who the investigator believes that their parents/guardians can and will comply with the requirements of the protocol should be enrolled in the PMS.

• A male or female infant from the age of 6 weeks at the time of the first vaccination.

• Written informed consent obtained from the parent or guardian of the infant.

Exclusion Criteria:

• At the time of PMS entry, the contraindications and precautions of use indicated in the prescribing information should be checked and the infant must not be included in the PMS if there is any contraindication. Any changes in the locally approved Prescribing Information must be implemented immediately.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Seoul		Korea, Republic of	122-896

Sponsors and Collaborators

• GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Full CSR posting.

Publications

None provided.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT00750893
• Other Study ID Numbers: 111700
• First Posted: Sep 11, 2008
• Last Update Posted: Mar 3, 2020
• Last Verified: Feb 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by GlaxoSmithKline: Gastroenteritis
• Additional relevant MeSH terms: Rotavirus Infections

Study Results

Participant Flow

Recruitment Details	This post marketing study (PMS) covered a period of 6 consecutive years. Results were presented for Years 1, 2, 3, 4, 5 (Year [Y] 1 & Y2 data combined and presented at the Y2 time point and Y3 & Y4 data combined and presented at the Y4 time point) along with consolidated surveillance data from Y1- Y6 timepoint.
Pre-assignment Detail	Consolidated participant flow and baseline measure data were given for Years 1 to 6 time point in order to account for all the subjects participating in this study.

Arm/Group Title	Rotarix Group
Arm/Group Description	Subjects who received 2 oral doses of Rotarix. The first dose was administered before the age of 6 weeks and the second one at least 4 weeks after, preferably before the age of 16 weeks. The 2 doses had to be given before 24 weeks of age.
Period Title: Overall Study
STARTED	3111
COMPLETED	2569
NOT COMPLETED	542

Baseline Characteristics

Arm/Group Title	Rotarix Group
Arm/Group Description	Subjects who received 2 oral doses of Rotarix. The first dose was administered before the age of 6 weeks and the second one at least 4 weeks after, preferably before the age of 16 weeks. The 2 doses had to be given before 24 weeks of age.
Overall Participants	3111
Age (weeks) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [weeks]	9.6 (2.22)
Sex: Female, Male (Count of Participants)
Female	1525 49%
Male	1586 51%
Race/Ethnicity, Customized (Count of Participants)
Korean	3107 99.9%
Chinese	2 0.1%
Japanese	2 0.1%

Outcome Measures

1. Primary Outcome

Title	Number of Subjects Reporting Solicited General Symptoms
Description	Solicited general symptoms assessed include cough, diarrhoea, irritability, loss of appetite, temperature and vomiting.
Time Frame	During the 8-day follow-up period after each vaccine dose for Year 1 & Year 2 study period

Outcome Measure Data

Analysis Population Description

Analysis was performed on the Total Vaccinated Cohort, which included all vaccinated subjects with at least one dose of Rotarix vaccine administration documented and for whom data were available at Year 1 and Year 2.

Arm/Group Title	Rotarix Group
Arm/Group Description	Subjects who received 2 oral doses of Rotarix. The first dose was administered before the age of 6 weeks and the second one at least 4 weeks after, preferably before the age of 16 weeks. The 2 doses had to be given before 24 weeks of age.
Measure Participants	876
Cough	204 6.6%
Diarrhoea	50 1.6%
Irritability	405 13%
Loss of appetite	259 8.3%
Temperature	135 4.3%
Vomiting	200 6.4%

2. Primary Outcome

Title	Number of Subjects Reporting Unsolicited Adverse Events (AEs) During the 31-day Follow-up Period After Each Vaccine Dose for Year 1 & Year 2 Study Period
Description	Unsolicited AE covers any AE reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms.
Time Frame	During the 31-day follow-up period after each vaccine dose for Year 1 & Year 2 study period

Outcome Measure Data

Analysis Population Description

Analysis was performed on the Total Vaccinated Cohort, which included all vaccinated subjects with at least one dose of Rotarix vaccine administration documented and for whom data were available at Year 1 and Year 2.

Arm/Group Title	Rotarix Group
Arm/Group Description	Subjects who received 2 oral doses of Rotarix. The first dose was administered before the age of 6 weeks and the second one at least 4 weeks after, preferably before the age of 16 weeks. The 2 doses had to be given before 24 weeks of age.
Measure Participants	876
Count of Participants [Participants]	334 10.7%

3. Primary Outcome

Title	Number of Subjects Reporting Unsolicited Adverse Events (AEs) During the 31-day Follow-up Period After Each Vaccine Dose for Year 3 & Year 4 Study Period
Description	Unsolicited AE covers any AE reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms.
Time Frame	During the 31-day follow-up period after each vaccine dose for Year 3 & Year 4 study period

Outcome Measure Data

Analysis Population Description

Analysis was performed on the Total Vaccinated Cohort, which included all vaccinated subjects with at least one dose of Rotarix vaccine administration documented and for whom data were available at Year 3 and Year 4.

Arm/Group Title	Rotarix Group
Arm/Group Description	Subjects who received 2 oral doses of Rotarix. The first dose was administered before the age of 6 weeks and the second one at least 4 weeks after, preferably before the age of 16 weeks. The 2 doses had to be given before 24 weeks of age.
Measure Participants	1052
Count of Participants [Participants]	413 13.3%

4. Primary Outcome

Title	Number of Subjects Reporting Unsolicited Adverse Events (AEs) During the 31-day Follow-up Period After Each Vaccine Dose for Year 5 Study Period
Description	Unsolicited AE covers any AE reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms.
Time Frame	During the 31 day follow-up period after each vaccine dose for Year 5 study period

Outcome Measure Data

Analysis Population Description

Analysis was performed on the Total Vaccinated Cohort, which included all vaccinated subjects with at least one dose of Rotarix vaccine administration documented and for whom data were available at Year 5.

Arm/Group Title	Rotarix Group
Arm/Group Description	Subjects who received 2 oral doses of Rotarix. The first dose was administered before the age of 6 weeks and the second one at least 4 weeks after, preferably before the age of 16 weeks. The 2 doses had to be given before 24 weeks of age.
Measure Participants	708
Count of Participants [Participants]	254 8.2%

5. Primary Outcome

Title	Number of Subjects Reporting Unsolicited Adverse Events (AEs) During the 31-day Follow-up Period After Each Vaccine Dose for Year 1 to Year 6 Study Period
Description	Unsolicited AE covers any AE reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms.
Time Frame	During the 31-day follow-up period after each vaccine dose for Year 1 to Year 6 study period

Outcome Measure Data

Analysis Population Description

Analysis was performed on the Total Vaccinated Cohort, which included all vaccinated subjects with at least one dose of Rotarix vaccine administration documented and for whom data were available for the Year 1 to Year 6 study period.

Arm/Group Title	Rotarix Group
Arm/Group Description	Subjects who received 2 oral doses of Rotarix. The first dose was administered before the age of 6 weeks and the second one at least 4 weeks after, preferably before the age of 16 weeks. The 2 doses had to be given before 24 weeks of age.
Measure Participants	3111
Count of Participants [Participants]	1201 38.6%

6. Primary Outcome

Title	Number of Subjects Reporting Serious Adverse Events (SAEs) During the Post-marketing Study Period for Year 1 & Year 2 Study Period
Description	SAEs assessed include medical occurrences that resulted in death, were life-threatening, required hospitalization or prolongation of hospitalization, resulted in disability/incapacity or were a congenital anomaly/birth defect in the offspring of a study subject.
Time Frame	During the post-marketing study period for Year 1 & Year 2 study period

Outcome Measure Data

Analysis Population Description

Analysis was performed on the Total Vaccinated Cohort, which included all vaccinated subjects with at least one dose of Rotarix vaccine administration documented for whom data were available at Year 1 and Year 2.

Arm/Group Title	Rotarix Group
Arm/Group Description	Subjects who received 2 oral doses of Rotarix. The first dose was administered before the age of 6 weeks and the second one at least 4 weeks after, preferably before the age of 16 weeks. The 2 doses had to be given before 24 weeks of age.
Measure Participants	876
Count of Participants [Participants]	6 0.2%

7. Primary Outcome

Title	Number of Subjects Reporting Serious Adverse Events (SAEs) During the Post-marketing Study Period for Year 3 & Year 4 Study Period
Description	SAEs assessed include medical occurrences that resulted in death, were life-threatening, required hospitalization or prolongation of hospitalization, resulted in disability/incapacity or were a congenital anomaly/birth defect in the offspring of a study subject.
Time Frame	During the post-marketing study period for Year 3 & Year 4 study period

Outcome Measure Data

Analysis Population Description

Analysis was performed on the Total Vaccinated Cohort, which included all vaccinated subjects with at least one dose of Rotarix vaccine administration documented for whom data were available at Year 3 and Year 4.

Arm/Group Title	Rotarix Group
Arm/Group Description	Subjects who received 2 oral doses of Rotarix. The first dose was administered before the age of 6 weeks and the second one at least 4 weeks after, preferably before the age of 16 weeks. The 2 doses had to be given before 24 weeks of age.
Measure Participants	1052
Count of Participants [Participants]	13 0.4%

8. Primary Outcome

Title	Number of Subjects Reporting Serious Adverse Events (SAEs) During the Post-marketing Study Period for Year 5 Study Period
Description	SAEs assessed include medical occurrences that resulted in death, were life-threatening, required hospitalization or prolongation of hospitalization, resulted in disability/incapacity or were a congenital anomaly/birth defect in the offspring of a study subject.
Time Frame	During the post-marketing study period for Year 5 study period

Outcome Measure Data

Analysis Population Description

Analysis was performed on the Total Vaccinated Cohort, which included all vaccinated subjects with at least one dose of Rotarix vaccine administration documented for whom data were available at Year 5.

Arm/Group Title	Rotarix Group
Arm/Group Description	Subjects who received 2 oral doses of Rotarix. The first dose was administered before the age of 6 weeks and the second one at least 4 weeks after, preferably before the age of 16 weeks. The 2 doses had to be given before 24 weeks of age.
Measure Participants	708
Count of Participants [Participants]	4 0.1%

9. Primary Outcome

Title	Number of Subjects Reporting Serious Adverse Events (SAEs) During the Post-marketing Study Period for Year 1 to Year 6 Study Period
Description	SAEs assessed include medical occurrences that resulted in death, were life-threatening, required hospitalization or prolongation of hospitalization, resulted in disability/incapacity or were a congenital anomaly/birth defect in the offspring of a study subject.
Time Frame	During the post-marketing study period for Year 1 to Year 6 study period

Outcome Measure Data

Analysis Population Description

Analysis was performed on the Total Vaccinated Cohort, which included all vaccinated subjects with at least one dose of Rotarix vaccine administration documented and for whom data were available for Year 1 to Year 6 study period.

Arm/Group Title	Rotarix Group
Arm/Group Description	Subjects who received 2 oral doses of Rotarix. The first dose was administered before the age of 6 weeks and the second one at least 4 weeks after, preferably before the age of 16 weeks. The 2 doses had to be given before 24 weeks of age.
Measure Participants	3111
Count of Participants [Participants]	26 0.8%

Adverse Events

Time Frame	Serious adverse events: during Years 1, 2, 3, 4, 5 and 6 post-marketing study period. Systematically and non-systematically assessed frequent adverse events: during the 8-day and 31-day follow-up period after each vaccine dose, respectively.
Adverse Event Reporting Description	Classification for AEs was performed differently across the study period, according to MedDRA preferred terms until Year 4, and to World Health Organisation's Adverse Reactions Terminology (WHO ART) Dictionary for Year 5 and for the consolidated results from Year 1 to Year 6. The data presented within the Adverse Events section represent the consolidated results for Year 1 to Year 6 period.
Arm/Group Title	Rotarix Group
Arm/Group Description	Subjects who received 2 oral doses of Rotarix. The first dose was administered before the age of 6 weeks and the second one at least 4 weeks after, preferably before the age of 16 weeks. The 2 doses had to be given before 24 weeks of age.
All Cause Mortality
	Rotarix Group
	Affected / at Risk (%)	# Events
Total	0/3111 (0%)
Serious Adverse Events
	Rotarix Group
	Affected / at Risk (%)	# Events
Total	26/3111 (0.8%)
Ear and labyrinth disorders
Otitis Media	4/3111 (0.1%)
Gastrointestinal disorders
Ileus paralytic	1/3111 (0%)
Colitis	1/3111 (0%)
Gastroenteritis	3/3111 (0.1%)
Gastroenteritis viral	1/3111 (0%)
Cytomegalovirus Gastrointestinal Infection	1/3111 (0%)
General disorders
Fever	1/3111 (0%)
Infections and infestations
Sepsis	1/3111 (0%)
Renal and urinary disorders
Hydronephrosis	1/3111 (0%)
Urinary tract infection	3/3111 (0.1%)
Respiratory, thoracic and mediastinal disorders
Upper respiratory tract infection	1/3111 (0%)
Bronchopneumonia	1/3111 (0%)
Pneumonia	4/3111 (0.1%)
Bronchiolitis	9/3111 (0.3%)
Croup	1/3111 (0%)
Bronchitis	2/3111 (0.1%)
Pneumonia viral	1/3111 (0%)
Other (Not Including Serious) Adverse Events
	Rotarix Group
	Affected / at Risk (%)	# Events
Total	684/3111 (22%)
Gastrointestinal disorders
Vomiting	200/3111 (6.4%)
General disorders
Irritability	405/3111 (13%)
Metabolism and nutrition disorders
Decreased appetite	259/3111 (8.3%)
Respiratory, thoracic and mediastinal disorders
Cough	204/3111 (6.6%)
Upper respiratory tract infection	268/3111 (8.6%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.