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Rotavirus VaccinePhase 2NCT04344054

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

A Phase 2 study testing RV3-BB, Trivalent P2-VP8 and Rotarix in people with Rotavirus Vaccine, run by PATH at 2 sites in South Africa.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages Up to 56 daysHealthy volunteers can take part
Conditions the study is for
Rotavirus Vaccine
What is being tested?
RV3-BB, Trivalent P2-VP8 and Rotarix
Could I receive a placebo?
No, everyone receives an active treatment
How many people
850 participants
Where
2 sitesSouth Africa
Study dates
22 Feb 2021to 9 Sep 2022
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Up to 56 days
  • All sexes
  • Healthy volunteers accepted
  • Child

Who may be able to join

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

Who cannot join

  • Presence of diarrhea or vomiting in the previous 72 hours or on the day of enrollment; temporary exclusion.
  • Presence of acute disease at the time of enrollment; temporary exclusion.
  • Presence of fever on the day of enrollment (axillary temperature ≥37.5 °C); temporary exclusion.
  • Concurrent participation in another clinical trial throughout the entire timeframe of this study.
  • 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.
  • History of premature birth (<37 weeks gestation) as per the investigator's assessment.
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  • History of congenital abdominal disorders, intussusception, abdominal surgery.
  • Known or suspected impairment of immunological function based on medical history and physical examination.
  • Prior receipt of or intent to receive age specified EPI vaccines including rotavirus vaccine, outside of the study center and during study participation.
  • A known sensitivity or allergy to any components of the study medication.
  • Clinically detectable congenital anomaly or genetic defect.
  • History of persistent diarrhea (defined as diarrhea more than 14 days). Not applicable for selection of Cohort A.
  • Participant's parent/LAR not able, available or willing to accept active follow-up by the study staff.
  • Receipt of any immunoglobulin therapy and/or blood products since birth or planned administration during the study period.
  • 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.
  • 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.

Trial locations and contacts

2 sites in 1 country.

South Africa2 sites

  • Wits RHI Shandukani Research Centre

    Johannesburg, Gauteng, 2003

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

    Johannesburg, Gauteng, 2013

Other trials in South Africa

About this study

Official title: A Phase II, Observer-blinded, Randomized, Active-controlled Study to Examine the Immunogenicity and Safety of Rotarix® and RV3-BB When Co-administered/Boosted With Trivalent P2-VP8 Subunit Rotavirus Vaccine Candidate in Healthy Infants in South Africa

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.

Read the detailed description

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.

Being tested
RV3-BB, Trivalent P2-VP8, Rotarix, RV3-BB birth dose, Trivalent P2-VP8 Booster dose
Keywords
Parental Rotavirus Vaccine, Rotarix, RV3-BB, TV P2-VP8, Mixed schedule, Rotavirus Booster

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • RV3-BBBiological

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

  • Trivalent P2-VP8Biological

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

  • RotarixBiological

    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.

  • RV3-BB birth doseBiological

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

  • Trivalent P2-VP8 Booster doseBiological

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

Study groups in NCT04344054
Study groupRoleWhat they receive
Arm 1ExperimentalRV3-BB/TV P2-VP8 boost
Receives: Biological: RV3-BB; Biological: Trivalent P2-VP8 Booster dose
Arm 2ExperimentalRV3-BB/TV P2-VP8 co-administered
Receives: Biological: RV3-BB; Biological: Trivalent P2-VP8
Arm 3ExperimentalRV3-BB primed TV P2-VP8
Receives: Biological: Trivalent P2-VP8; Biological: RV3-BB birth dose
Arm 4ExperimentalRotarix®/TV P2-VP8 Boost
Receives: Biological: Rotarix; Biological: Trivalent P2-VP8 Booster dose
Arm 5ExperimentalRotarix®/TV P2-VP8 co-administered
Receives: Biological: Trivalent P2-VP8; Biological: Rotarix
Arm 6ExperimentalTV P2-VP8 alone
Receives: Biological: Trivalent P2-VP8

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Immunogenicity 1

    Immunogenicity: Between-arm comparisons (all comparisons except for LORV alone vs TV P2-VP8-boosted LORV) will be performed by computing Geometric Mean Concentration (GMC) ratios for LORV-specific serum anti-rotavirus IgA antibody and corresponding confidence intervals.

    Measured: 4 weeks after the last vaccination within each regimen being compared.

  2. Immunogenicity 2

    Immunogenicity: Within-arm evaluation of boosting will be performed using the geometric mean fold rise (GMFR) of LORV-specific serum anti-rotavirus IgA antibody and its corresponding confidence interval.

    Measured: 4 weeks after completion of LORV (Week 14)

  3. Immunogenicity 3

    Immunogenicity: Within-arm evaluation of boosting will be performed using the geometric mean fold rise (GMFR) of LORV-specific serum antirotavirus IgA antibody and its corresponding confidence interval.

    Measured: 4 weeks post-boost (Week 18)

  4. Safety 1: Percentage of participants reporting immediate adverse events after each vaccination

    Immediate Adverse Events: Percentage of participants reporting immediate adverse events after each vaccination

    Measured: within 30 minutes' post-vaccination

  5. Safety 2: Percentage of participants reporting solicited post-vaccination reactogenicity

    Solicited Adverse Events: Percentage of participants reporting solicited post-vaccination reactogenicity

    Measured: 7 day period after each vaccination

  6. Safety 3: Percentage of participants reporting unsolicited AEs

    Unsolicited Adverse Events: Percentage of participants reporting unsolicited AEs

    Measured: from first vaccination through 4 weeks after the last vaccination

  7. Safety 4: Percentage of participants reporting SAEs

    Serious Adverse Events: Percentage of participants reporting SAEs

    Measured: from first vaccination through 4 weeks after the last vaccination of each study participant

Secondary outcomes (8)

  1. Immunogenicity 1

    Between- and within-arm comparisons for serum IgA will be performed using GMC ratios and GMFRs, respectively

    Measured: 4 weeks after the last vaccination within each regimen being compared

  2. Immunogenicity 2

    Seroconversion rate for anti-rotavirus IgA antibodies.

    Measured: 4 weeks after the last vaccination

  3. Immunogenicity 3

    Seropositivity rate for anti-rotavirus IgA antibodies.

    Measured: 4 weeks after the last vaccination

  4. Immunogenicity 4

    Seroresponse rate for anti-rotavirus IgA antibodies.

    Measured: 4 weeks after the last vaccination

  5. Immunogenicity 5

    Geometric Mean Concentration (GMC) ratios and Geometric Mean Fold Rise (GMFR) for serum anti-P2-VP8 IgG antibodies.

    Measured: 4 weeks after the last vaccination

  6. Immunogenicity 6

    Seroresponse rate for serum anti-P2-VP8 IgG antibodies.

    Measured: 4 weeks after the last vaccination

  7. Immunogenicity 7

    Geometric Mean Titers (GMT) ratios and Geometric Mean Fold Rise (GMFR) of TV P2-VP8-specific serum neutralizing antibodies.

    Measured: 4 weeks after the last vaccination

  8. Immunogenicity 8

    Seroresponse rate of TV P2-VP8-specific serum neutralizing antibodies

    Measured: 4 weeks after the last vaccination

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Apr 2020
  2. Study start22 Feb 2021
  3. Primary completion6 Sep 2022
  4. Study completion9 Sep 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
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.
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
850 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04344054
Sponsor's protocol ID
CVIA 082
Status last verified
Nov 2022
First submitted
6 Apr 2020
Last updated
29 Nov 2022
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: Summary results for primary and secondary objectives to be posted at CT.gov.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing RV3-BB, Trivalent P2-VP8 and Rotarix in people with Rotavirus Vaccine, run by PATH at 2 sites in South Africa.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 29 Nov 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in South Africa. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Immunogenicity 1 (time frame: 4 weeks after the last vaccination within each regimen being compared.). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04344054.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Nov 2022.

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