A Dose-escalating Study to Evaluate the Immunogenicity and Safety of Rotavin-M1 Vaccine in Healthy Infants

NCT ID: NCT01377571

Last Updated: 2016-07-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 200 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-10-31
• Study Completion Date: 2010-04-30

Brief Summary

The purpose of this study is to evaluate the safety and immunogenicity of Rotavin-M1 produced by the Center for Research and Production of Vaccines and Biologicals (POLYVAC) in infants in Vietnam. In addition, we evaluate different dosages and schedules to determine the best regimen to test in a clinical trial.

Detailed Description

Rotavirus (RV) is the most important cause of acute gastroenteritis in children worldwide. In Vietnam rotavirus causes an estimated 122,000-140,000 hospitalizations and 2900-5400 deaths per year among children under 5 years of age (1). Over the past 13 years, sentinel hospital surveillance identified rotavirus in 44%-62% of children admitted for the treatment of acute diarrhea in Vietnam (2-4). Such a high burden of disease justified accelerated development of a new and locally manufactured vaccine against rotavirus in Vietnam. It is estimated that if a vaccine was introduced in the current childhood immunization schedule, it could reduce severe rotavirus disease by about 60% or more given current vaccine efficacies and coverage (5).

The Government of Vietnam has pursued a policy to encourage local vaccine production so the country could be self-reliant with affordable vaccines for its population (6). Over the past decades, several locally produced vaccines for poliomyelitis, cholera, Japanese encephalitis, and Diphtheria-Pertussis-Tetanus have contributed to the reduction in the prevalence of these diseases and to the eradication of polio over the past decade. While two commercial rotavirus vaccines, RotarixTM (GSK, Belgium) and RotaTeq® (Merck), have both been tested in Vietnam, neither is currently available at an affordable cost for the national program. Therefore, the candidate vaccine, Rotavin-M1, was developed in order to fill this need for a more affordable vaccine for Vietnamese children (6). This vaccine is similar to RotarixTM, and was developed by selecting a common G1P[8] strain and attenuating it through serial passages and plaque purification in qualified Vero cells under GLP conditions.

Conditions

Diarrhea; Fever; Nausea; Vomit; Irritability

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Blinding Strategy: QUADRUPLE

Study Groups

Rotavin2H

2 doses of Rotavin-M1 vaccine, 106.3FFU/dose, 2-month separation between doses

Group Type: EXPERIMENTAL

Rotarix

Intervention Type: BIOLOGICAL

2 doses of Rotarix vaccine, 106.5CID/dose, 1-month interval between doses

Rotavin2L

2 doses of Rotavin-M1 vaccine, 106.0FFU/dose, 2-month interval between doses

Group Type: EXPERIMENTAL

Rotarix

Intervention Type: BIOLOGICAL

2 doses of Rotarix vaccine, 106.5CID/dose, 1-month interval between doses

Rotavin3H

3 doses of Rotavin-M1 vaccine, 106.3FFU/dose, 1-month interval between doses

Group Type: EXPERIMENTAL

Rotarix

Intervention Type: BIOLOGICAL

2 doses of Rotarix vaccine, 106.5CID/dose, 1-month interval between doses

Rotavin3L

3 doses of Rotavin-M1, 106.0FFU/dose, 1-month interval between doses

Group Type: EXPERIMENTAL

Rotarix

Intervention Type: BIOLOGICAL

2 doses of Rotarix vaccine, 106.5CID/dose, 1-month interval between doses

Interventions

Rotarix

2 doses of Rotarix vaccine, 106.5CID/dose, 1-month interval between doses

Intervention Type: BIOLOGICAL

Other Intervention Names

RotarixTM, GSK biologicals

Eligibility Criteria

Inclusion Criteria

• At dose 1

1. A healthy male or female, 6 to 12 weeks of age (42 days to 84 days of age).

2. Full term gestation (>=37 weeks).

3. Birth weight of the subject should be >=2.5 kg.

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

5. Did not use any dose of Rota virus vaccine.

6. Written informed consent obtained from the parent or guardian of the subject.

• At dose 2

1. Received dose 1.

2. Oral informed consent obtained from the parent or guardian of the subject for continuing participate the study.

• At dose 3

1. Received both dose 1 and dose 2.

2. Oral informed consent obtained from the parent or guardian of the subject for continuing participate the study.

Exclusion Criteria

• At dose 1

1. Has a chronic disease (cardiovascular, liver, kidney disease).

2. Acute disease at the time of enrolment.

3. Administering corticosteroids (> 1mg/kg/day).

4. Received any immunosuppressive therapy within 4 week before vaccination (Administration of immunoglobulins and/or any blood product or corticosteroids for >2 weeks).

5. Immunosuppressive or immunodeficient condition.

6. Family has immunosuppressive or immunodeficient condition medical history.

7. History of high fever convulsion.

8. Allergic or reaction with any component of vaccine, includes anaphylactic shock with any antibiotic.

9. Preterm of gestation delivery (gestation period < 37 weeks).

10. Low birth weight (<2.5 kg).

11. Fever (axillary temperature >38oC) within 3 days before or on the day of vaccination.

12. Malnutrition.

13. Has any type of blood disorder, leukemia, or malignant tumor which can affect the bone marrow or lymph system.

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

• At dose 2

1. Acute disease at the time of 2nd dose.

2. Administering corticosteroids (> 1mg/kg/day).

3. Received any immunosuppressive therapy within 4 week before vaccination (Administration of immunoglobulins and/or any blood product or corticosteroids for >2 weeks).

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

5. Fever (axillary temperature >38oC) within 3 days before or on the day of vaccination.

6. Has any type of blood disorder, leukemia, or malignant tumor which can affect the bone marrow or lymph system.

7. Use of any investigational or non-registered product (unlicensed drug or vaccine) other than the study vaccine during the study period.

• At dose 3

1. Acute disease at the time of 3rd dose.

2. Administering corticosteroids (> 1mg/kg/day).

3. Received any immunosuppressive therapy within 4 week before vaccination (Administration of immunoglobulins and/or any blood product or corticosteroids for >2 weeks).

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

5. Fever (axillary temperature >38oC) within 3 days before or on the day of vaccination.

6. Has any type of blood disorder, leukemia, or malignant tumor which can affect the bone marrow or lymph system.

7. Use of any investigational or non-registered product (unlicensed drug or vaccine) other than the study vaccine during the study period.

• Minimum Eligible Age: 6 Weeks
• Maximum Eligible Age: 12 Weeks
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Center for Research and Production of Vaccines and Biologicals, Vietnam

OTHER_GOV

Sponsor Role: collaborator

National Institute of Hygiene and Epidemiology, Vietnam

OTHER

Sponsor Role: lead

Responsible Party

Dang Duc Anh

Director

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Anh D Dang, PhD.

Role: PRINCIPAL_INVESTIGATOR

The National Institute of Hygiene and Epidemiology

Thiem D Vu, MD., PhD.

Role: PRINCIPAL_INVESTIGATOR

The National Institute of Hygiene and Epidemiology

Locations

Preventive Medicine center

Thanh Sơn, Phu Tho, Vietnam

Countries

Vietnam

References

Anh DD, Thiem VD, Fischer TK, Canh DG, Minh TT, Tho le H, Van Man N, Luan le T, Kilgore P, von Seidlein L, Glass RI. The burden of rotavirus diarrhea in Khanh Hoa Province, Vietnam: baseline assessment for a rotavirus vaccine trial. Pediatr Infect Dis J. 2006 Jan;25(1):37-40. doi: 10.1097/01.inf.0000195635.05186.52.

Reference Type: BACKGROUND

PMID: 16395100 (View on PubMed)

Van Man N, Luan le T, Trach DD, Thanh NT, Van Tu P, Long NT, Anh DD, Fischer TK, Ivanoff B, Gentsch JR, Glass RI; Vietnam Rotavirus Surveillance Network. Epidemiological profile and burden of rotavirus diarrhea in Vietnam: 5 years of sentinel hospital surveillance, 1998-2003. J Infect Dis. 2005 Sep 1;192 Suppl 1:S127-32. doi: 10.1086/431501.

Reference Type: BACKGROUND

PMID: 16088796 (View on PubMed)

Ngo TC, Nguyen BM, Dang DA, Nguyen HT, Nguyen TT, Tran VN, Vu TT, Ogino M, Alam MM, Nakagomi T, Nakagomi O, Yamashiro T. Molecular epidemiology of rotavirus diarrhoea among children in Haiphong, Vietnam: the emergence of G3 rotavirus. Vaccine. 2009 Nov 20;27 Suppl 5:F75-80. doi: 10.1016/j.vaccine.2009.08.074.

Reference Type: BACKGROUND

PMID: 19931725 (View on PubMed)

Nguyen TA, Yagyu F, Okame M, Phan TG, Trinh QD, Yan H, Hoang KT, Cao AT, Le Hoang P, Okitsu S, Ushijima H. Diversity of viruses associated with acute gastroenteritis in children hospitalized with diarrhea in Ho Chi Minh City, Vietnam. J Med Virol. 2007 May;79(5):582-90. doi: 10.1002/jmv.20857.

Reference Type: BACKGROUND

PMID: 17385670 (View on PubMed)

Kim SY, Goldie SJ, Salomon JA. Cost-effectiveness of Rotavirus vaccination in Vietnam. BMC Public Health. 2009 Jan 21;9:29. doi: 10.1186/1471-2458-9-29.

Reference Type: BACKGROUND

PMID: 19159483 (View on PubMed)

Luan le T, Trang NV, Phuong NM, Nguyen HT, Ngo HT, Nguyen HT, Tran HB, Dang HN, Dang AD, Gentsch JR, Wang Y, Esona MD, Glass RI, Steele AD, Kilgore PE, Nguyen MV, Jiang B, Nguyen HD. Development and characterization of candidate rotavirus vaccine strains derived from children with diarrhoea in Vietnam. Vaccine. 2009 Nov 20;27 Suppl 5:F130-8. doi: 10.1016/j.vaccine.2009.08.086.

Reference Type: BACKGROUND

PMID: 19931712 (View on PubMed)

Dang DA, Nguyen VT, Vu DT, Nguyen TH, Nguyen DM, Yuhuan W, Baoming J, Nguyen DH, Le TL; Rotavin-M1 Vaccine Trial Group. A dose-escalation safety and immunogenicity study of a new live attenuated human rotavirus vaccine (Rotavin-M1) in Vietnamese children. Vaccine. 2012 Apr 27;30 Suppl 1:A114-21. doi: 10.1016/j.vaccine.2011.07.118.

Reference Type: DERIVED

PMID: 22520120 (View on PubMed)

Other Identifiers

KC.10.33/06-10

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

Rotavin02

Identifier Type: -

Identifier Source: org_study_id