Phase I/II Descending Age Study of P2VP8 Subunit Parenteral Rotavirus Vaccine in Healthy Toddlers and Infants

NCT02109484 | Completed Phase 1 Results

• 1 other identifier: VAC-013
• Study Type: interventional
• Target: 204
• Locations: 1 country
• Sites: 1

Brief Summary

This is is a study of a parenteral rotavirus vaccine (P2-VP8 subunit rotavirus vaccine). The study will examine the safety and immunogenicity of this vaccine first in healthy South African toddlers. If the safety profile is deemed appropriate, the study will continue to explore the safety and immunogenicity of the vaccine in healthy South African infants. The primary safety hypothesis is that the P2-VP8 subunit rotavirus vaccine is safe and well-tolerated in healthy toddlers and infants. The primary immunogenicity hypothesis is that the P2-VP8 subunit rotavirus vaccine is immunogenic in infant participants and will induce an immune response in at least 80% of participants in at least one of the study groups.

Conditions

Evaluation of a Rotavirus Vaccine

Outcome Measures

Primary Outcomes (6)

• Number of Participants With Vaccine Induced Reactions

  Maximum severity of all local reactions or systemic reactogenicity after any vaccination

  7 days following each dose

• Number of Participants With Serious Adverse Events

  Number of participants experiencing a Serious Adverse Event within 28 days of a vaccination and at any time during the study

  within 28 days of a study dose and at any time

• Number of Participants Reporting Any Non-Serious Adverse Event

  all adverse events will be recorded over the duration of the 6 month follow up period.

  6 mo following first vaccination

• Number/Percentage of Infant Participants With Anti-P2-VP8 IgA to P[8] Seroresponse.

  Seroresponse is defined as 4 fold rise in Geometric Mean Titer (GMT) between pre-(baseline) and post vaccination (4 weeks after third vaccination). Confidence intervals are displayed as percentages.

  Baseline to day 84

• Number/Percentage of Infants With Anti-P2-VP8 IgG to P[8] Seroresponses

  Seroresponse is defined as 4 fold rise in Geometric Mean Titer (GMT) between pre-(baseline) and post vaccination (4 weeks after third injection).An unadjusted serioresponse was defined as an increase of 4 times or more in titers between baseline and 4 weeks after the 3rd injection. Adjusted IgG and neutralizing antibody post injection titres accounted for the decay in maternal antibodies using the half-life calculated from participants in the placebo group with detectable baseline titers higher than those at the post injection visit.

  Baseline to day 84

• Number/Percentage of Infants With Neutralizing Antibody Response to WA Strain (G1[P8])

  Seroresponse is defined as 4 fold rise in Geometric Mean Titer (GMT) between pre-(baseline) and post vaccination (4 weeks after third injection).An unadjusted serioresponse was defined as an increase of 4 times or more in titers between baseline and 4 weeks after the 3rd injection. Adjusted IgG and neutralizing antibody post injection titres accounted for the decay in maternal antibodies using the half-life calculated from participants in the placebo group with detectable baseline titers higher than those at the post injection visit.

  Baseline to Day 84

Secondary Outcomes (1)

• Rotavirus Shedding After Administration of Rotarix in Infants Receiving 3 Doses of Vaccine or Placebo.

  Rotarix vaccination on Day 84 to day 91

Study Arms (8)

Cohort A P2-VP8 30 mcg

EXPERIMENTAL

Cohort A toddlers (24-35 mo) receiving P2-VP8 Subunit Vaccine (30 mcg)

Biological: P2-VP8 Subunit Vaccine 30 mcg

Cohort A Placebo

PLACEBO COMPARATOR

Cohort A toddlers (24-35 mo)

Other: Placebo

Cohort A P2-VP8 60 mcg

EXPERIMENTAL

Cohort A toddlers (24-35 mo) receiving high dose P2-VP8 Subunit Vaccine (60mcg)

Biological: P2-VP8 Subunit Vaccine 60mcg

Cohort B P2-VP8 10mcg

EXPERIMENTAL

Cohort B infants receiving P2-VP8 Subunit Vaccine (10mcg)

Biological: P2-VP8 Subunit Vaccine 10mcg

Cohort B placebo

PLACEBO COMPARATOR

Cohort B infants aged 6 to \< 8 weeks receiving placebo

Other: Placebo

Cohort B P2-VP8 30mcg

EXPERIMENTAL

Cohort B infants aged 6 to \< 8 weeks receiving P2-VP8 Subunit Vaccine (30mcg)

Biological: P2-VP8 Subunit Vaccine 30 mcg

Cohort B1 P2-VP8 60mcg

EXPERIMENTAL

Cohort B1 Infants aged 6 to \< 8 weeks receiving P2-VP8 Subunit Vaccine (60mcg)

Biological: P2-VP8 Subunit Vaccine 60mcg

Cohort A P2-VP8 10mcg

EXPERIMENTAL

Cohort A toddlers (24-35 mo) receiving P2VP8 Subunit Vaccine (10mcg)

Biological: P2-VP8 Subunit Vaccine 10mcg

Interventions

P2-VP8 Subunit Vaccine 10mcg BIOLOGICAL

10 mcg

Cohort A P2-VP8 10mcg; Cohort B P2-VP8 10mcg

P2-VP8 Subunit Vaccine 30 mcg BIOLOGICAL

30 mcg

Cohort A P2-VP8 30 mcg; Cohort B P2-VP8 30mcg

P2-VP8 Subunit Vaccine 60mcg BIOLOGICAL

60 mcg

Cohort A P2-VP8 60 mcg; Cohort B1 P2-VP8 60mcg

Placebo OTHER

Cohort A Placebo; Cohort B placebo

Eligibility Criteria

• Age: 6 Weeks - 35 Months
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• healthy infants/toddlers as established by medical history and clinical examination before entering study
• age:
• toddler cohort: \> or = 2 and \<3 years old at the time of enrollment
• infant cohort: \> or = 6 and \<8 weeks at the time of enrollment
• parental ability and willingness to provide informed consent
• parental intention to remain in the area with the child during the study period.

You may not qualify if:

• Presence of fever on the day of enrollment
• Acute disease at the time of enrollment
• Concurrent participation in another clinical trial throughout the entire timeframe for this study
• Presence of malnutrition or 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 that would compromise the participant's health or is likely to result in nonconformance to the protocol
• For infant cohort, history of premature birth (\<37 weeks gestation)
• History of congenital abdominal disorders, intussusception, or abdominal surgery
• Known or suspected impairment of immunological function based on medical history and physical examination
• For infant cohort only, prior receipt of rotavirus vaccine
• A known sensitivity or allergy to any components of the study vaccine
• History of anaphylactic reaction
• Major congenital or genetic defect
• Participant's parents not able, available or willing to accept active weekly follow-up by the study staff
• Has received 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 immunosuppressant medications, including corticosteroids. Infants on inhaled or topical steroids may be permitted to participate in the study
• Any medical condition in the parents/infant that, in the judgment of the investigator, would interfere with or serves as a contraindication to protocol adherence or a participant's parents' ability to give informed consent

Sponsors & Collaborators

• PATH: lead

Study Sites (1)

Respiratory and Meningeal Pathogens Research Unit (RMPRU)

Johannesburg, Gauteng, 2013, South Africa

Location

Related Publications (2)

• Koen A, Jose L, Madhi SA, Fix A, Cryz S, Groome MJ. Neutrophil Counts in Healthy South African Infants: Implications for Enrollment and Adverse Event Grading in Clinical Trials in an African Setting. J Pediatr X. 2019 Spring;1:100005. doi: 10.1016/j.ympdx.2019.100005.

  PMID: 32734176 DERIVED

• Groome MJ, Koen A, Fix A, Page N, Jose L, Madhi SA, McNeal M, Dally L, Cho I, Power M, Flores J, Cryz S. Safety and immunogenicity of a parenteral P2-VP8-P[8] subunit rotavirus vaccine in toddlers and infants in South Africa: a randomised, double-blind, placebo-controlled trial. Lancet Infect Dis. 2017 Aug;17(8):843-853. doi: 10.1016/S1473-3099(17)30242-6. Epub 2017 May 5.

  PMID: 28483414 DERIVED

Results Point of Contact

• Title: Michelle J. Groome, MD, PhD
• Organization: Chris Hani Baragwanath Academic Hospital

groomem@rmpru.co.za

+27 11 983 4283

Study Officials

• Michelle Groome

  SAMRC Respiratory and Meningeal Pathogen Research Unit

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 4, 2014
• First Posted: April 10, 2014
• Study Start: March 1, 2014
• Primary Completion: November 1, 2015
• Study Completion: November 1, 2015
• Last Updated: December 13, 2017
• Results First Posted: December 13, 2017

Record last verified: 2017-11

Locations

ZA (1)