Clinical trial NCT02109484: Phase I/II Descending Age Study of P2VP8 Subunit Parenteral Rotavirus Vaccine in Healthy Toddlers and Infants
Official title: Phase I/II Descending Age Double-blinded Randomized Placebo-controlled Dose Escalation Study to Examine the Safety Reactogenicity Tolerability & Immunogenicity of the P2-VP8 Subunit Parenteral Rotavirus Vaccine in Healthy Toddlers & Infants
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Evaluation of a Rotavirus Vaccine
Lead sponsor: PATH
Sponsor class: OTHER
First posted: 2014-04-10
Enrollment: 204
Sex: ALL
Minimum age (years): 6
Maximum age (years): 35
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.


Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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
* HIV infection

  * For toddlers, to be assessed by HIV ELISA
  * For infants, to be assessed by PCR, if mother is not known to be negative (negative test result between 24 weeks gestation and screening)

Primary outcomes:
measure: Number of Participants With Vaccine Induced Reactions
timeFrame: 7 days following each dose
measure: Number of Participants With Serious Adverse Events
timeFrame: within 28 days of a study dose and at any time
measure: Number of Participants Reporting Any Non-Serious Adverse Event
timeFrame: 6 mo following first vaccination
measure: Number/Percentage of Infant Participants With Anti-P2-VP8 IgA to P[8] Seroresponse.
timeFrame: Baseline to day 84
measure: Number/Percentage of Infants With Anti-P2-VP8 IgG to P[8] Seroresponses
timeFrame: Baseline to day 84
measure: Number/Percentage of Infants With Neutralizing Antibody Response to WA Strain (G1[P8])
timeFrame: Baseline to Day 84
Secondary outcomes:
measure: Rotavirus Shedding After Administration of Rotarix in Infants Receiving 3 Doses of Vaccine or Placebo.
timeFrame: Rotarix vaccination on Day 84 to day 91
Other outcomes:
Locations:
city: Johannesburg
country: South Africa
facility: Respiratory and Meningeal Pathogens Research Unit (RMPRU)
state: Gauteng
Study officials:
affiliation: SAMRC Respiratory and Meningeal Pathogen Research Unit
name: Michelle Groome
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.