Study to Evaluate Immunogenicity, Reactogenicity and Safety of Rotarix™ Vaccine in Korean Infants

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00969228
• Collaborator: (none)
• Enrollment: 684
• Locations: 18
• Arms: 2
• Actual Duration (Months): 10.9
• Patients Per Site: 38
• Patients Per Site Per Month: 3.5

Study Details

Study Description

Brief Summary

The aim of this study is to assess the immunogenicity, reactogenicity and safety of the human rotavirus (HRV) Rotarix ™ vaccine when administered in healthy infants aged approximately 6-12 weeks at the time of first vaccination.

Condition or Disease	Intervention/Treatment	Phase
Infections, Rotavirus; Rotavirus Vaccines	Biological: Rotarix ™; Biological: Placebo	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 684 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Immunogenicity, Reactogenicity and Safety Study to Evaluate Two Doses of the Lyophilised Formulation of the Human Rotavirus (HRV) Vaccine When Administered to Healthy Korean Infants Previously Uninfected With HRV
• Actual Study Start Date: Aug 25, 2009
• Actual Primary Completion Date: Jul 23, 2010
• Actual Study Completion Date: Jul 23, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Rotarix Group Subjects received 2 oral doses of Rotarix according to a 0, 1 or 2-month schedule.	Biological: Rotarix ™; Two oral doses
Placebo Comparator: Placebo Group Subjects received 2 oral doses of placebo according to a 0, 1 or 2-month schedule.	Biological: Placebo; Two oral doses

Outcome Measures

Primary Outcome Measures

1. Number of Subjects Seroconverted for Anti-rotavirus Immunoglobulin A [One month after the second vaccine dose]

   Seroconversion is defined as the appearance of antibodies with concentrations greater than or equal to 20 units per milliliter (U/mL) in the serum of subjects seronegative before vaccination.

Secondary Outcome Measures

1. Serum Anti-rotavirus Immunoglobulin A Antibody Concentrations [One month after the second vaccine dose]

   Concentrations are given as Geometric Mean Concentrations (GMCs). Note: In the Placebo Group the value was below the assay cut-off (20 units per milliliter).

2. Number of Subjects Reporting Solicited Symptoms [During the 8-day (Day 0 - Day 7) follow-up period after each vaccine dose.]

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

3. Number of Subjects Reporting Unsolicited Adverse Events (AEs) [During the 31-day (Day 0 - Day 30) follow-up period after each vaccine dose]

   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 Serious Adverse Events (SAEs) [Throughout the study period (2-3 months).]

   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.

5. Number of Subjects Reporting Rotavirus Gastroenteritis Episode(s) [From Dose 1 up to 1 month after Dose 2.]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 6 Weeks to 12 Weeks
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

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

• A male or female between, and including, 6 to 12 weeks of age at the time of the first dose of the vaccination.

• Written informed consent obtained from the parents or guardians of the subject.

• Healthy subjects as established by medical history and clinical examination before entering into the study.

• Born after a normal gestation period of between 37 and 41 weeks + 6 days inclusive.

• Subjects for whom the vaccination history is available from vaccination diary cards or medical charts.

Exclusion Criteria:

• Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine(s) within 30 days preceding the dose of study vaccine, or planned use during the study period.

• Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs since birth.

• Planned administration/ administration of a vaccine not foreseen by the study protocol within 30 days of the first dose of vaccine with the exception of the routine infant vaccines.

• Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational product.

• Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination.

• Any clinically significant history of chronic gastrointestinal disease including any uncorrected congenital malformation of the gastrointestinal tract or other serious medical condition as determined by the investigator.

• History of allergic disease or reactions likely to be exacerbated by any component of the vaccine.

• Acute disease at the time of enrolment.

• Administration of immunoglobulins and/or any blood products since birth or planned administration during the study period.

• Gastroenteritis (GE) within 7 days preceding the study vaccine administration.

• Previous confirmed occurrence of RV GE.

• Previous vaccination with rotavirus vaccine or planned use during the study period.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Busan		Korea, Republic of	614-735
2	GSK Investigational Site	Daegu		Korea, Republic of	700-712
3	GSK Investigational Site	Daegu		Korea, Republic of	701-600
4	GSK Investigational Site	Daejeon		Korea, Republic of	301-723
5	GSK Investigational Site	Daejeon		Korea, Republic of
6	GSK Investigational Site	Goyang		Korea, Republic of
7	GSK Investigational Site	Gwangju		Korea, Republic of	501-717
8	GSK Investigational Site	Iksan		Korea, Republic of	570-711
9	GSK Investigational Site	Incheon		Korea, Republic of	400-711
10	GSK Investigational Site	Jeonju Jeonbuk		Korea, Republic of	561-712
11	GSK Investigational Site	Kwangju		Korea, Republic of
12	GSK Investigational Site	Seoul		Korea, Republic of	130-702
13	GSK Investigational Site	Seoul		Korea, Republic of	135-710
14	GSK Investigational Site	Seoul		Korea, Republic of	138-736
15	GSK Investigational Site	Seoul		Korea, Republic of	139-707
16	GSK Investigational Site	Seoul		Korea, Republic of	150-719
17	GSK Investigational Site	Seoul		Korea, Republic of
18	GSK Investigational Site	Suwon, Kyonggi-do		Korea, Republic of	443-721

Sponsors and Collaborators

• GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Publications

• Buyse H, Vinals C, Karkada N, Han HH. The human rotavirus vaccine Rotarix™ in infants: an integrated analysis of safety and reactogenicity. Hum Vaccin Immunother. 2014;10(1):19-24. doi: 10.4161/hv.26476. Epub 2013 Oct 8.
• Kim JS et al. Assessment of immunogenicity, reactogenicity and safety of human rotavirus vaccine RIX4414 in Korean infants. Abstract presented at the Korean Society of Pediatric Infectious Diseases - 2011 Autumn Conference (KSPID). Seoul, S Korea, 12-15 November 2011.
• Kim JS, Bae CW, Lee KY, Park MS, Choi YY, Kim KN, Kim JD, Park WS, Sin JB, Kim EA, Lee SG, Kim CS, Cha SH, Hong YJ, Shin SM, Shim GH, Choi KM, Yang JW, Liu A, Suryakiran PV, Han HH. Immunogenicity, reactogenicity and safety of a human rotavirus vaccine (RIX4414) in Korean infants: a randomized, double-blind, placebo-controlled, phase IV study. Hum Vaccin Immunother. 2012 Jun;8(6):806-12. doi: 10.4161/hv.19853. Epub 2012 Jun 1.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT00969228
• Other Study ID Numbers: 112269; 2015-001545-81
• First Posted: Sep 1, 2009
• Last Update Posted: Jan 18, 2020
• Last Verified: Jan 1, 2020

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by GlaxoSmithKline: Gastroenteritis
• Additional relevant MeSH terms: Rotavirus Infections

Study Results

Participant Flow

Arm/Group Title	Rotarix Group	Placebo Group
Arm/Group Description	Subjects received 2 oral doses of Rotarix according to a 0, 1 or 2-month schedule.	Subjects received 2 oral doses of placebo according to a 0, 1 or 2-month schedule.
Period Title: Overall Study
STARTED	508	176
COMPLETED	465	162
NOT COMPLETED	43	14

Baseline Characteristics

Arm/Group Title	Rotarix Group	Placebo Group	Total
Arm/Group Description	Subjects received 2 oral doses of Rotarix according to a 0, 1 or 2-month schedule.	Subjects received 2 oral doses of placebo according to a 0, 1 or 2-month schedule.	Total of all reporting groups
Overall Participants	508	176	684
Age (Weeks) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Weeks]	8.8 (1.25)	8.9 (1.26)	8.8 (1.25)
Sex: Female, Male (Count of Participants)
Female	231 45.5%	79 44.9%	310 45.3%
Male	277 54.5%	97 55.1%	374 54.7%

Outcome Measures

1. Primary Outcome

Title	Number of Subjects Seroconverted for Anti-rotavirus Immunoglobulin A
Description	Seroconversion is defined as the appearance of antibodies with concentrations greater than or equal to 20 units per milliliter (U/mL) in the serum of subjects seronegative before vaccination.
Time Frame	One month after the second vaccine dose

Outcome Measure Data

Analysis Population Description

Analysis was performed on the According-to-Protocol (ATP) cohort for immunogenicity, on subjects with available results.

Arm/Group Title	Rotarix Group	Placebo Group
Arm/Group Description	Subjects received 2 oral doses of Rotarix according to a 0, 1 or 2-month schedule.	Subjects received 2 oral doses of placebo according to a 0, 1 or 2-month schedule.
Measure Participants	318	114
Number [subjects]	280	5

2. Secondary Outcome

Title	Serum Anti-rotavirus Immunoglobulin A Antibody Concentrations
Description	Concentrations are given as Geometric Mean Concentrations (GMCs). Note: In the Placebo Group the value was below the assay cut-off (20 units per milliliter).
Time Frame	One month after the second vaccine dose

Outcome Measure Data

Analysis Population Description

Analysis was performed on the According-to-Protocol (ATP) cohort for immunogenicity, on subjects with available results.

Arm/Group Title	Rotarix Group	Placebo Group
Arm/Group Description	Subjects received 2 oral doses of Rotarix according to a 0, 1 or 2-month schedule.	Subjects received 2 oral doses of placebo according to a 0, 1 or 2-month schedule.
Measure Participants	280	114
Geometric Mean (95% Confidence Interval) [units per milliliter (U/mL)]	208.5	NA

3. Secondary Outcome

Title	Number of Subjects Reporting Solicited Symptoms
Description	Solicited symptoms assessed include cough, diarrhoea, irritability, loss of appetite , fever and vomiting.
Time Frame	During the 8-day (Day 0 - Day 7) follow-up period after each vaccine dose.

Outcome Measure Data

Analysis Population Description

Analysis was performed on the Total Vaccinated Cohort.

Arm/Group Title	Rotarix Group	Placebo Group
Arm/Group Description	Subjects received 2 oral doses of Rotarix according to a 0, 1 or 2-month schedule.	Subjects received 2 oral doses of placebo according to a 0, 1 or 2-month schedule.
Measure Participants	508	176
Cough	180	66
Diarrhoea	20	7
Irritability	290	106
Loss of appetite	174	60
Fever	67	18
Vomiting	95	36

4. Secondary Outcome

Title	Number of Subjects Reporting Unsolicited Adverse Events (AEs)
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 (Day 0 - Day 30) follow-up period after each vaccine dose

Outcome Measure Data

Analysis Population Description

Analysis was performed on the Total Vaccinated Cohort.

Arm/Group Title	Rotarix Group	Placebo Group
Arm/Group Description	Subjects received 2 oral doses of Rotarix according to a 0, 1 or 2-month schedule.	Subjects received 2 oral doses of placebo according to a 0, 1 or 2-month schedule.
Measure Participants	508	176
Number [subjects]	148	59

5. Secondary Outcome

Title	Number of Subjects Reporting Serious Adverse Events (SAEs)
Description	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.
Time Frame	Throughout the study period (2-3 months).

Outcome Measure Data

Analysis Population Description

Analysis was performed on the Total Vaccinated Cohort.

Arm/Group Title	Rotarix Group	Placebo Group
Arm/Group Description	Subjects received 2 oral doses of Rotarix according to a 0, 1 or 2-month schedule.	Subjects received 2 oral doses of placebo according to a 0, 1 or 2-month schedule.
Measure Participants	508	176
Number [subjects]	17	13

6. Secondary Outcome

Title	Number of Subjects Reporting Rotavirus Gastroenteritis Episode(s)
Time Frame	From Dose 1 up to 1 month after Dose 2.

Outcome Measure Data

Analysis Population Description

Analysis was performed on the Total Vaccinated Cohort.

Arm/Group Title	Rotarix Group	Placebo Group
Arm/Group Description	Subjects received 2 oral doses of Rotarix according to a 0, 1 or 2-month schedule.	Subjects received 2 oral doses of placebo according to a 0, 1 or 2-month schedule.
Measure Participants	508	176
Number [subjects]	0	0

Adverse Events

Time Frame	Solicited symptoms: during the 8-day follow-up period after each dose of vaccine. Unsolicited adverse events: during the 31-day follow-up after any dose of Rotarix vaccine or placebo. Serious adverse events: during the entire study period (2-3 months)
Arm/Group Title	Rotarix Group		Placebo Group
Arm/Group Description	Subjects received 2 oral doses of Rotarix according to a 0, 1 or 2-month schedule.		Subjects received 2 oral doses of placebo according to a 0, 1 or 2-month schedule.
All Cause Mortality
	Rotarix Group		Placebo Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Rotarix Group		Placebo Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	17/508 (3.3%)		13/176 (7.4%)
Congenital, familial and genetic disorders
Solitary kidney	0/508 (0%)		1/176 (0.6%)
Gastrointestinal disorders
Abdominal pain	0/508 (0%)		1/176 (0.6%)
Diarrhoea	1/508 (0.2%)		0/176 (0%)
General disorders
Pyrexia	4/508 (0.8%)		0/176 (0%)
Infections and infestations
Bronchiolitis	6/508 (1.2%)		5/176 (2.8%)
Gastroenteritis	5/508 (1%)		4/176 (2.3%)
Urinary tract infection	2/508 (0.4%)		2/176 (1.1%)
Bronchitis	1/508 (0.2%)		1/176 (0.6%)
Bronchopneumonia	2/508 (0.4%)		0/176 (0%)
Escherichia urinary tract infection	0/508 (0%)		1/176 (0.6%)
Hepatitis viral	0/508 (0%)		1/176 (0.6%)
Otitis externa	1/508 (0.2%)		0/176 (0%)
Otitis media	1/508 (0.2%)		0/176 (0%)
Pharyngitis	1/508 (0.2%)		0/176 (0%)
Pneumonia	0/508 (0%)		1/176 (0.6%)
Pneumonia bacterial	1/508 (0.2%)		0/176 (0%)
Pyelonephritis acute	0/508 (0%)		1/176 (0.6%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lymphoma	1/508 (0.2%)		0/176 (0%)
Respiratory, thoracic and mediastinal disorders
Pneumonia apiration	0/508 (0%)		1/176 (0.6%)
Other (Not Including Serious) Adverse Events
	Rotarix Group		Placebo Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	367/508 (72.2%)		134/176 (76.1%)
General disorders
Cough	180/508 (35.4%)		66/176 (37.5%)
Irritability	290/508 (57.1%)		106/176 (60.2%)
Loss of appetite	174/508 (34.3%)		60/176 (34.1%)
Fever	67/508 (13.2%)		18/176 (10.2%)
Vomiting	95/508 (18.7%)		36/176 (20.5%)
Infections and infestations
Nasopharynigitis	29/508 (5.7%)		17/176 (9.7%)

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.