A Phase II, Observer-blinded, Randomized, Active-controlled Study to Examine the Immunogenicity and Safety of Rotarix® and RV3-BB when Coadministered/Boosted with Trivalent P2-VP8 Subunit Rotavirus Vaccine Candidate in Healthy Infants in South Africa.


Diarrhea is the second-leading cause of infectious disease death worldwide among children under the age of five. Rotavirus is the leading cause of severe diarrhea, resulting in an estimated 215,000 (range: 197,000–233,000) deaths in 2013 which corresponds to 3.4% of all deaths in children

Primary Objectives


1. To assess and compare the immunogenicity of each standalone LORV to matching regimens that include co-administration with TV P2-VP8, measured by LORV-specific serum anti-rotavirus Ig

A antibody concentration.

2. To evaluate the boosting effect of TV P2-VP8 in infants receiving a standalone LORV primary series, measured by LORV-specific serum antirotavirus Ig

A antibody concentration.

3. To assess and compare the immunogenicity of a birth dose of RV3-BB boosted with TV P2-VP8 to TV P2-VP8 administered alone, measured by RV3-BB specific serum anti-rotavirus Ig

A antibody concentration.

Safety To assess the safety and tolerability of LORVs and TV P2-VP8 when administered independently, concomitantly or in a prime-boost regimen

Study Design

• This is a phase II, observer-blinded, multi-center, randomized and activecontrolled 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 with Cohort A enrolling infants at birth (0-6 days) and Cohort B enrolling infants 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 (see below for cohort designation). Cohort A participants 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 in antero-lateral aspect of thigh. 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. To maintain the blind within cohorts, infants allocated to the arms receiving only an oral rotavirus vaccine or only TV P2-VP8 vaccine on Visit 2 and 3 will receive a dose of injectable placebo or an oral placebo (PLC-OA or PLC-OB depending on the cohort), respectively, such that all infants will receive both an oral and injectable administration during these visits. • The initiation of enrollment within a cohort will be staggered, with the target to initiate enrolment of Cohort B after 6 weeks of initiating enrolment in Cohort A, in order to increase the likelihood that participants are similar in terms of baseline characteristics and any environmental exposure to wild-type rotavirus that may be circulating.

• A blood sample will be obtained from all the participating infants prevaccination at Visit (V) 1 (for Cohort A)/V2 (for Cohort B) and postvaccination at week 14 and week 18 in both cohorts (appendix I). All serum samples will be tested for serum IgA antibodies using two separate ELISA assays that employ viral lysates derived from either rotavirus strains 89-12 or RV3. Serum samples will also be tested to quantitate anti-P2-VP8 IgG binding antibodies and neutralizing antibodies against the 3 rotavirus vaccine strains expressing P[4], P[6] and P[8] antigens contained in the TV P2-VP8 vaccine.

• Active follow-up for vaccine reactogenicity (solicited reactions) over the 7-day period following each vaccination will be conducted on all participants receiving study vaccination. In addition, surveillance for unsolicited AEs will be carried out over the period between first study vaccination and Visit 5 (approximately 28 days after last vaccination with IP) and SAEs will be collected until the study is completed.

• All participants in all the study arms will receive a challenge dose of Rotarix® at visit 5. Participants in study arms which received non-licensed candidate vaccines (RV3-BB and/or TV P2-VP8; arms 1-3 and 6 in Table 1 below) will receive another (second) supplemental doses of Rotarix® (standard of care in South Africa) with an interval of 4 weeks (Visit 6). Participants in other study arms will receive PLC-OB at this visit to maintain blinding. Safety of supplemental doses of Rotarix® will be ascertained by following up these infants for SAEs at Visit 6 and a phone call as Visit 7.

• Stool sample will be collected in all participants 4 and 7 days after the challenge dose with Rotarix® at Visit 5 to evaluate vaccine viral shedding. Viral shedding will be investigated by EIA and PCR in stool specimens collected at these timepoints.

• The partially blinded safety data will be reviewed by a PSRT (Protocol Safety Review Team) and by an independent Data and Safety Monitoring Board (DSMB). In addition, the DSMB will also perform unblinded data review at periodic intervals and as necessary on request by the PSRT team. .

Study Population

Infants aged 0-6 days or 6-8 weeks will be enrolled in this study from two clinical sites in South Africa


Prof Lee Fairlie, Principal Investigator

Dr Gabriella Benade

Dr Masebole Masenya

Dr Faeezah Patel

Dr Elizea Horne

Dr Mrinmayee Dhar

Dr Alden Geldenhuys



Latest Update: 23 August 2021

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