Clinical trial NCT03703336: Phase III Study of Liquid Formulation of ROTAVIN
Official title: A Phase III, Randomized, Partially Double- Blind, Active Control Study to Compare the Immunogenicity and Safety of a Liquid Formulation of ROTAVIN With the Currently Licensed Frozen Formulation of the Vaccine (ROTAVIN-M1), in Healthy Vietnamese Infants
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Diarrhea
Diarrhea Rotavirus
Keywords: ROTAVIN
Rotavirus vaccine
Rotavirus
Diarrhea
Lead sponsor: Center for Research and Production of Vaccines and Biologicals, Vietnam
Sponsor class: OTHER_GOV
Collaborators: name: PATH
name: National Institute of Hygiene and Epidemiology, Vietnam
name: Children's Hospital Medical Center, Cincinnati
First posted: 2018-10-11
Enrollment: 825
Sex: ALL
Minimum age (years): 60
Maximum age (years): 91
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Eligible infants will be randomized to receive either ROTAVIN or ROTAVIN-M1 vaccines in the ratio of 2:1.
Primary purpose: PREVENTION

Brief summary: This study is conducted to demonstrate non-inferiority in the immunogenicity of the liquid formulation of ROTAVIN in comparison to currently licensed frozen formulation of the vaccine (ROTAVIN-M1), 28 days after the second vaccination when administered as two dose series starting at 2-3 months of age.

The study will also assess the reactogenicity of the vaccine 7 days after each vaccination and safety from first vaccination up to 4 weeks after the last vaccination.

Detailed description: The study is designed as a phase III, randomized, partially double-blinded, active controlled study with two groups of infants receiving vaccines at the ratio of 2:1 (liquid formulation of ROTAVIN to frozen formulation ROTAVIN-M1), to compare their immunogenicity and safety. Two doses of vaccine will be administered 8 weeks apart with the first vaccine administration between 60-91 days of age. All childhood vaccines as per the Expanded Program for Immunization of the Government of Vietnam (including Diphtheria, Tetanus, Pertussis, Haemophilus influenzae type b and Hepatitis B vaccine (DTwPHib-HepB), and Oral Polio Vaccine at at 2, 3 and 4 months of age) will be allowed as per the immunization schedule.

Active surveillance for vaccine reactogenicity (solicited reactions) over the 7-day period after each vaccination, unsolicited adverse events (AEs) for 4 weeks after each vaccination and serious adverse events (SAEs) including intussusception over the period between first vaccination and four weeks after the last vaccination will be conducted for all infants.

This trial will generate immunogenicity and safety data which would be submitted to Ministry of Health in Vietnam for license of new formulation of ROTAVIN vaccine.

Eligibility criteria: Inclusion Criteria:

1. Healthy infants as established by medical history and clinical examination before entering the study.
2. Age: 60-91 days (both days inclusive) at the time of enrollment.
3. Parental/legally acceptable representative ability and willingness to provide written informed consent.
4. Parent/legally acceptable representative who intends to remain in the area with the child during the study period.

Exclusion Criteria:

1. Presence of diarrhea or vomiting in the previous 72 hours or on the day of enrollment (temporary exclusion).
2. Presence of fever on the day of enrollment (temporary exclusion).
3. Acute disease at the time of enrollment (temporary exclusion).
4. Concurrent participation in another clinical trial at any point throughout the entire time frame for this study.
5. Presence of significant malnutrition (weight-for-height z-score \< -3 SD median)
6. Presence of any systemic disorder (cardiovascular, pulmonary, hepatic, renal, gastrointestinal, hematological, endocrine, immunological, dermatological, neurological, cancer, or autoimmune disease) as determined by medical history and / or physical examination which would compromise the participant's health or is likely to result in nonconformance to the protocol.
7. History of congenital abdominal disorders, intussusception, or abdominal surgery.
8. Known or suspected impairment of immunological function based on medical history and physical examination.
9. Household contact with an immunosuppressed individual or pregnant woman.
10. Prior receipt of rotavirus or an intent to receive this vaccine from outside of the study center during study participation.
11. Prior receipt of Expanded Program on Immunization (EPI) vaccination during past 7 days or plan to receive them within next 7 days.
12. A known sensitivity or allergy to any components of the study vaccine.
13. History of allergy to antibiotic kanamycin.
14. Clinically detectable significant congenital or genetic defect.
15. History of persistent diarrhea (defined as diarrhea that lasts 14 days or longer).
16. Receipt of immunoglobulin therapy and / or blood products since birth or planned administration during the study period.
17. History of chronic administration (defined as more than 14 days) of immunosuppressants including corticosteroids. Infants on inhaled or topical steroids may be permitted to participate in the study.
18. Any medical condition in the parent/legally acceptable representative or infant which, in the judgment of the Investigator, would interfere with or serves as a contraindication to protocol adherence.

Primary outcomes:
measure: Geometric Mean Concentration (GMC) of Serum Anti-rotavirus Immunoglobulin A (IgA) Antibodies 28 Days After Second Vaccination
timeFrame: Day 85 (28 days after the second vaccination)
measure: Number of Participants With Solicited Reactions Within 7 Days of Vaccination
timeFrame: 7 days after each vaccination (Days 1 to 8 and 57 to 64)
Secondary outcomes:
measure: Percentage of Participants With Seroconversion 28 Days After the Second Vaccination
timeFrame: 28 days after the second vaccination (Day 85)
measure: Percentage of Participants With Seropositivity at Baseline and 28 Days After the Second Vaccination
timeFrame: Baseline (Day 1) and at 28 days after the second vaccination (Day 85)
measure: Number of Participants With Immediate Adverse Events (AEs)
timeFrame: Within 30 minutes after each vaccination on Day 1 and Day 57
measure: Number of Participants With Unsolicited Adverse Events
timeFrame: From vaccination through 28 days after each dose (Days 1 to 28 and 57 to 85)
measure: Number of Participants With Serious Adverse Events Including Intussusception
timeFrame: From first vaccination through 28 days after the last vaccination; 85 days
Other outcomes:
Locations:
city: Nam Dinh
country: Vietnam
facility: CDC Nam Dinh
city: Quang Ninh
country: Vietnam
facility: CDC Quang Ninh
Study officials:
affiliation: PATH India
name: Niraj Rathi, MD
role: STUDY_DIRECTOR
References:
citation: Thiem VD, Anh DD, Ha VH, Hien ND, Huong NT, Nga NT, Thang TC, McNeal MM, Meyer N, Pham HL, Huong NM, Gompana G, Cassels F, Tang Y, Flores J, Rathi N. Safety and immunogenicity of two formulations of rotavirus vaccine in Vietnamese infants. Vaccine. 2021 Jul 22;39(32):4463-4470. doi: 10.1016/j.vaccine.2021.06.056. Epub 2021 Jul 1.