Mixed Schedule Study of Live Oral Rotavirus Vaccines and Trivalent P2-VP8 Subunit Rotavirus Vaccine

NCT ID: NCT04344054

Last Updated: 2022-11-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

850 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-02-22

Study Completion Date

2022-09-09

Brief Summary

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The study will evaluate safety and immunogenicity of LORV (Rotarix and RV3-BB) when TV P2-VP8, a parentally administered rotavirus vaccine is administered either concomitantly or as a prime/boost model. Participants would be newborn babies or infants approximately at 6 weeks of age ta the time of enrollment. The vaccines will be administered at birth (only for one cohort) and at 6, 10 and 14 weeks. Immune response will be assessed prior to first vaccination, 14 weeks and at 18 weeks of age. The study will also evaluate the shedding of Rotarix virus after a challenge dose administered 28 days after last investigational product administration. Safety assessments will be conducted throughout the study duration.

Detailed Description

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This is a phase II, observer-blinded, multi-center, randomized and active-controlled study enrolling healthy infants 0-6 days of age or 6-8 weeks of age. The study will enroll infants in six arms divided into two cohorts enrolling infants at birth (0-6 days) and approximately 6 weeks of age. Within each cohort, the enrolled infants will be randomized to the three arms in a ratio of 6:6:5. Participants in Cohort A will receive: RV3-BB/TV P2-VP8 boost (arm 1); RV3-BB/TV P2-VP8 co-administered (arm 2); RV3-BB primed TV P2-VP8 (arm 3), while participants in Cohort B will receive: Rotarix®/TV P2-VP8 Boost (arm 4); Rotarix®/TV P2-VP8 co-administered (arm 5); or TV P2-VP8 alone (arm 6). Rotarix® and RV3-BB will be administered orally whereas TV P2-VP8 will be administered intramuscularly. The study will be conducted as an observer-blinded study wherein the treatment assignment within a cohort will be blinded, although allocation to a cohort will be unblinded due to the difference in age at enrolment between the two cohorts. Participants will receive a dose of injectable or oral placebo to maintain blinding.

A blood sample will be obtained from all the participating infants pre-vaccination and post-vaccination at week 14 and week 18 in both cohorts. All serum samples will be tested for serum IgA binding antibody by ELISA using virus lysates prepared from RV3-BB and 89-12 strains. Additionally, anti-P2-VP8 IgG binding and serum neutralizing antibody levels to each of the 3 strains of rotavirus from which TV P2-VP8 is derived will be determined.

Vaccine safety will be evaluated by 1) recording the immediate adverse events for 30 minutes after immunization, 2) solicited adverse events for 7 days after each study vaccination, 3) unsolicited events for 28 days after each dose, and 4) serious adverse events 28 days after last dose of study vaccination.

All participants in all the study arms will receive a challenge dose of Rotarix® at visit 5following completion of primary series of vaccinations. Stool sample will be collected to evaluate vaccine viral shedding.

The primary objective of the study is to compare the immunogenicity in participants receiving LORV co-administration with TV P2- VP8 or those receiving the TV P2-VP8 booster after receiving a standalone LORV primary series with the standalone LORV. A comparison of immune responses to birth dose of RV3-BB boosted with TV P2-VP8 to TV P2-VP8 administered alone will also be conducted. All primary immunogenicity analysis will be based on LORV specific serum anti-rotavirus IgA antibody concentration. Placebo administration (oral and parenteral) were appropriately placed to facilitate blinding.

The secondary objective were to compare the different treatment regimens within a cohort using serum anti-P2-VP8 IgG antibodies and neutralizing antibodies to each of the 3 strains of rotavirus from which TV P2-VP8 is derived.

Conditions

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Rotavirus Vaccine

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

The study will enroll infants in six arms divided into two cohorts enrolling infants at birth (0-6 days) or at approximately 6 weeks of age. Within each cohort, the enrolled infants will be randomized to the three arms in a ratio of 6:6:5.
Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
The participants will receive vaccine as per the assigned treatment to the arm to which he/she has been randomized.

Study Groups

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Arm 1

RV3-BB/TV P2-VP8 boost

Group Type EXPERIMENTAL

RV3-BB

Intervention Type BIOLOGICAL

1.0 mL of the thawed rotavirus vaccine to be administered orally at birth, 6 weeks and 10 weeks of age

Trivalent P2-VP8 Booster dose

Intervention Type BIOLOGICAL

0.5 mL of vaccine containing 90 μg of the TV P2-VP8 antigen; IM; at 14 weeks of age

Arm 2

RV3-BB/TV P2-VP8 co-administered

Group Type EXPERIMENTAL

RV3-BB

Intervention Type BIOLOGICAL

1.0 mL of the thawed rotavirus vaccine to be administered orally at birth, 6 weeks and 10 weeks of age

Trivalent P2-VP8

Intervention Type BIOLOGICAL

0.5 mL of vaccine containing 90 μg of the TV P2-VP8 antigen; IM; at approximately 6, 10 and 14 weeks of age

Arm 3

RV3-BB primed TV P2-VP8

Group Type EXPERIMENTAL

Trivalent P2-VP8

Intervention Type BIOLOGICAL

0.5 mL of vaccine containing 90 μg of the TV P2-VP8 antigen; IM; at approximately 6, 10 and 14 weeks of age

RV3-BB birth dose

Intervention Type BIOLOGICAL

1.0 mL of the thawed rotavirus vaccine to be administered orally at birth.

Arm 4

Rotarix®/TV P2-VP8 Boost

Group Type EXPERIMENTAL

Rotarix

Intervention Type BIOLOGICAL

1.5 mL of the liquid vaccine containing the RIX4414 strain of human rotavirus vaccine to be administered orally at 6 weeks and 10 weeks of age.

Trivalent P2-VP8 Booster dose

Intervention Type BIOLOGICAL

0.5 mL of vaccine containing 90 μg of the TV P2-VP8 antigen; IM; at 14 weeks of age

Arm 5

Rotarix®/TV P2-VP8 co-administered

Group Type EXPERIMENTAL

Trivalent P2-VP8

Intervention Type BIOLOGICAL

0.5 mL of vaccine containing 90 μg of the TV P2-VP8 antigen; IM; at approximately 6, 10 and 14 weeks of age

Rotarix

Intervention Type BIOLOGICAL

1.5 mL of the liquid vaccine containing the RIX4414 strain of human rotavirus vaccine to be administered orally at 6 weeks and 10 weeks of age.

Arm 6

TV P2-VP8 alone

Group Type EXPERIMENTAL

Trivalent P2-VP8

Intervention Type BIOLOGICAL

0.5 mL of vaccine containing 90 μg of the TV P2-VP8 antigen; IM; at approximately 6, 10 and 14 weeks of age

Interventions

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RV3-BB

1.0 mL of the thawed rotavirus vaccine to be administered orally at birth, 6 weeks and 10 weeks of age

Intervention Type BIOLOGICAL

Trivalent P2-VP8

0.5 mL of vaccine containing 90 μg of the TV P2-VP8 antigen; IM; at approximately 6, 10 and 14 weeks of age

Intervention Type BIOLOGICAL

Rotarix

1.5 mL of the liquid vaccine containing the RIX4414 strain of human rotavirus vaccine to be administered orally at 6 weeks and 10 weeks of age.

Intervention Type BIOLOGICAL

RV3-BB birth dose

1.0 mL of the thawed rotavirus vaccine to be administered orally at birth.

Intervention Type BIOLOGICAL

Trivalent P2-VP8 Booster dose

0.5 mL of vaccine containing 90 μg of the TV P2-VP8 antigen; IM; at 14 weeks of age

Intervention Type BIOLOGICAL

Eligibility Criteria

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Inclusion Criteria

1. Healthy male and female infants as established by medical history and clinical examination at enrollment.
2. Age: ≤ 6 days old (Cohort A) or between the age of 6-8 weeks (42-56 days; inclusive) (Cohort B)
3. Birth weight of ≥ 2500 grams.
4. Parent's/legally acceptable representative's (LAR) ability and willingness to provide informed consent.
5. Parent/LAR confirms intention to stay in the area and bring their infant for the required study visits.

Exclusion Criteria

1. Presence of diarrhea or vomiting in the previous 72 hours or on the day of enrollment; temporary exclusion.
2. Presence of acute disease at the time of enrollment; temporary exclusion.
3. Presence of fever on the day of enrollment (axillary temperature ≥37.5 °C); temporary exclusion.
4. Concurrent participation in another clinical trial throughout the entire timeframe of this study.
5. 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 child's health or is likely to result in non-conformance to the protocol.
6. History of premature birth (\<37 weeks gestation) as per the investigator's assessment.
7. History of congenital abdominal disorders, intussusception, abdominal surgery.
8. Known or suspected impairment of immunological function based on medical history and physical examination.
9. Prior receipt of or intent to receive age specified EPI vaccines including rotavirus vaccine, outside of the study center and during study participation.
10. A known sensitivity or allergy to any components of the study medication.
11. Clinically detectable congenital anomaly or genetic defect.
12. History of persistent diarrhea (defined as diarrhea more than 14 days). Not applicable for selection of Cohort A.
13. Participant's parent/LAR not able, available or willing to accept active follow-up by the study staff.
14. Receipt of any immunoglobulin therapy and/or blood products since birth or planned administration during the study period.
15. History of chronic administration (defined as more than 14 days) of high doses of immunosuppressant including corticosteroids. Infants on inhaled or topical steroids may be permitted to participate in the study. Not applicable for selection of Cohort A.
16. Any medical condition in the parents/infants that, in the judgment of the investigator, would interfere with or serves as a contraindication to protocol adherence or a participant's parent's/LAR's ability to give informed consent.
Maximum Eligible Age

56 Days

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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SK Bioscience Co., Ltd.

INDUSTRY

Sponsor Role collaborator

Murdoch Childrens Research Institute

OTHER

Sponsor Role collaborator

Children's Hospital Medical Center, Cincinnati

OTHER

Sponsor Role collaborator

Bill and Melinda Gates Foundation

OTHER

Sponsor Role collaborator

PATH

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Stanley Cryz, PhD

Role: STUDY_DIRECTOR

PATH

Locations

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Wits RHI Shandukani Research Centre

Johannesburg, Gauteng, South Africa

Site Status

Vaccine and Infectious Diseases Analytics (VIDA) - formerly known as Respiratory and Meningococcal Pathogens Research Unit (RMPRU)

Johannesburg, Gauteng, South Africa

Site Status

Countries

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South Africa

Other Identifiers

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CVIA 082

Identifier Type: -

Identifier Source: org_study_id

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