Safety and Immunogenicity Study of Trivalent P2-VP8 Subunit Rotavirus Vaccine in Adults, Toddlers and Infants

NCT02646891 | Completed Phase 1 Results DMC

• 1 other identifier: VAC-041
• Study Type: interventional
• Target: 618
• Locations: 1 country
• Sites: 3

Brief Summary

This is is a study of a parenteral trivalent rotavirus vaccine (P2-VP8 subunit rotavirus vaccine). The study examined the safety and immunogenicity of three dose levels of this vaccine in healthy South African adults, toddlers and infants. Progression from one dose level to another and to the next age group population was based on the assessment of safety information from the lowest dose and older age group. The primary safety hypothesis is that the P2-VP8 subunit rotavirus vaccine is safe and well-tolerated. The primary immunogenicity hypothesis is that the trivalent P2-VP8 subunit rotavirus vaccine is immunogenic in infant participants and will induce an immune response to at least 2 of the 3 strains in 60% or more of participants in at least one of the study groups.

Conditions

Healthy

Keywords

Rotavirus Vaccine

Outcome Measures

Primary Outcomes (8)

• Number of Participants Experiencing Adverse Events (AE) Within 28 Days of Any Vaccination

  Any symptom starting after 7 days post any study injection was recorded as an adverse event. A serious adverse event (SAE) is any event that occurred from the first dose of study drug that resulted in any of the following outcomes: 1. Death 2. Life-threatening AE 3. Inpatient hospitalization or prolongation of existing hospitalization 4. Persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions 5. Congenital abnormality or birth defect 6. Important medical event that may not result in one of the above outcomes but may jeopardize the health of the study participant or require medical or surgical intervention to prevent one of the outcomes listed above. The severity of adverse events was graded from Mild (grade 1) to Life Threatening (grade 4). AEs related to study drug were those events for which there was a reasonable possibility that the study drug caused the event In the opinion of the site investigator.

  Up to 28 days after any vaccination (up to Day 28 for toddlers and up to Day 84 for infants and adults)

• Number of Participants With Local or Systemic Reactions Within 7 Day of Vaccination

  Reactogenicity data (solicited signs or symptoms) were assessed for 7 days after each injection. Participants and parents were instructed to assess and record daily local reactions (injection site pain/tenderness, redness, swelling, itching), as well as systemic signs and symptoms (fever, headache, vomiting, nausea, fatigue, chills and myalgia for adults; and fever, vomiting, decreased appetite, irritability, and decreased activity for toddlers and infants) in a participant memory aid. Reactions were graded on a scale from mild (Grade 1) to life-threatening (Grade 4). The overall number of participants who experienced any local or systemic reaction is reported. Grades are based on maximum severity per participant.

  7 days following each vaccination

• Number of Infants With Anti-P2-VP8 Immunoglobulin G (IgG) Seroresponse 4 Weeks After the Third Vaccination, by Vaccine Antigen

  Seroresponse was defined as a four-fold rise or greater in antibody titer between Baseline and 28 days after the third injection (Day 84). Measured by enzyme-linked immunosorbent assay (ELISA) and adjusted for decay in maternal IgG antibodies. The estimated maternal antibody half-life was derived from linear regression of Log2 transformed titers in placebo recipients from the combined infant cohorts.

  Day 84

• Number of Infants With Anti-P2-VP8 Immunoglobulin A (IgA) Seroresponse 4 Weeks After the Third Vaccination, by Vaccine Antigen

  Seroresponse was defined as a four-fold rise or greater in antibody titer between Baseline and 28 days after the final injection (Day 84). Measured by enzyme-linked immunosorbent assay (ELISA) to whole viral lysate.

  Day 84

• Number of Infants With Neutralizing Antibody Responses 4 Weeks After the Third Vaccination to Each Rotavirus Strain

  Neutralizing antibody response was defined as a ≥ 2.7-fold rise in antibody titer between Baseline and 28 days after the final injection (Day 84). Neutralizing antibodies to each of the three rotavirus strains from which the vaccine antigens were derived (Wa, DS-1, and 1076) were measured using a validated assay. For infants, antibody titer was adjusted for decay in maternal antibodies.

  Day 84

• Anti-P2-VP8 Immunoglobulin G (IgG) Geometric Mean Titers Among Infants, by Vaccine Antigen

  Measured by ELISA at Baseline, 28 days after the second injection (Day 56 pre-vaccination; secondary outcome) and 28 days after the third and final injection (Day 84; primary outcome).

  Baseline and Days 56 (pre-vaccination) and 84

• Anti-P2-VP8 Immunoglobulin A (IgA) Geometric Mean Titers Among Infants, by Vaccine Antigen

  Measured by ELISA at Baseline, 28 days after the second injection (Day 56 pre-vaccination; secondary outcome) and 28 days after the third and final injection (Day 84; primary outcome).

  Baseline and Days 56 (pre-vaccination) and 84

• Geometric Mean Titers of Neutralizing Antibody Against Rotavirus Strains Among Infants

  Neutralizing antibodies to each of the three rotavirus strains from which the vaccine antigens were derived (Wa, DS-1, and 1076) were measured at Baseline and 28 days after the second injection (Day 56 pre-vaccination; secondary outcome) and third injection (Day 84; primary outcome).

  Baseline and Days 56 (pre-vaccination) and 84

Secondary Outcomes (10)

• Number of Participants Experiencing Adverse Events (AE) Over the Entire Study Period

  Up to 6 months after the last injection (224 days for adults and infants; 168 days for toddlers)

• Number of Infants With Anti-P2-VP8 Immunoglobulin G (IgG) Seroresponse 4 Weeks After the Second Vaccination, by Vaccine Antigen

  Day 56, pre-vaccination

• Number of Infants With Anti-P2-VP8 Immunoglobulin A (IgA) Seroresponse 4 Weeks After the Second Vaccination, by Vaccine Antigen

  Day 56, pre-vaccination

• Number of Infants With Neutralizing Antibody Responses 4 Weeks After the Second Vaccination

  Day 56, prevaccination

• Number of Adults and Toddlers With Anti-P2-VP8 Immunoglobulin G (IgG) Seroresponse, by Vaccine Antigen

  Day 84 for adults; Day 28 for toddlers

Study Arms (10)

Adults: Placebo

PLACEBO COMPARATOR

Adults received three intramuscular injections of placebo four weeks apart on Days 0, 28, and 56.

Biological: Placebo

Adults: 30 µg P2-VP8

EXPERIMENTAL

Adults received three intramuscular injections of 30 µg trivalent P2-VP8 subunit rotavirus vaccine four weeks apart on Days 0, 28, and 56.

Biological: Trivalent P2-VP8 Subunit Rotavirus Vaccine

Adults: 90 µg P2-VP8

EXPERIMENTAL

Adults received three intramuscular injections of 90 µg trivalent P2-VP8 subunit rotavirus vaccine four weeks apart on Days 0, 28, and 56.

Biological: Trivalent P2-VP8 Subunit Rotavirus Vaccine

Toddlers: Placebo

PLACEBO COMPARATOR

Toddlers received one intramuscular injection of placebo on Day 0.

Biological: Placebo

Toddlers: 30 µg P2-VP8

EXPERIMENTAL

Toddlers received one intramuscular injection of 30 µg trivalent P2-VP8 subunit rotavirus vaccine on Day 0.

Biological: Trivalent P2-VP8 Subunit Rotavirus Vaccine

Toddlers: 90 µg P2-VP8

EXPERIMENTAL

Toddlers received one intramuscular injection of 90 µg trivalent P2-VP8 subunit rotavirus vaccine on Day 0.

Biological: Trivalent P2-VP8 Subunit Rotavirus Vaccine

Infants: Placebo

PLACEBO COMPARATOR

Infants received three intramuscular injections of placebo four weeks apart on Days 0, 28, and 56.

Biological: Placebo

Infants: 15 µg P2-VP8

EXPERIMENTAL

Infants received three intramuscular injections of 15 µg trivalent P2-VP8 subunit rotavirus vaccine four weeks apart on Days 0, 28, and 56.

Biological: Trivalent P2-VP8 Subunit Rotavirus Vaccine

Infants: 30 µg P2-VP8

EXPERIMENTAL

Infants received three intramuscular injections of 30 µg trivalent P2-VP8 subunit rotavirus vaccine four weeks apart on Days 0, 28, and 56.

Biological: Trivalent P2-VP8 Subunit Rotavirus Vaccine

Infants: 90 µg P2-VP8

EXPERIMENTAL

Infants received three intramuscular injections of 90 µg trivalent P2-VP8 subunit rotavirus vaccine four weeks apart on Days 0, 28, and 56.

Biological: Trivalent P2-VP8 Subunit Rotavirus Vaccine

Interventions

Trivalent P2-VP8 Subunit Rotavirus Vaccine BIOLOGICAL

Manufactured and supplied by the Walter Reed Army Institute of Research (WRAIR) Pilot Bioproduction Facility (BPF). The trivalent P2-VP8 vaccine was formulated as a sterile suspension containing a total of 360 µg of protein (120 µg of each P type) per mL adsorbed to aluminum hydroxide (1.125 mg of aluminum per mL in a phosphate buffer, pH 7).

Adults: 30 µg P2-VP8; Adults: 90 µg P2-VP8; Infants: 15 µg P2-VP8; Infants: 30 µg P2-VP8; Infants: 90 µg P2-VP8; Toddlers: 30 µg P2-VP8; Toddlers: 90 µg P2-VP8

Placebo BIOLOGICAL

Sodium Chloride 0.9%, USP for Injection

Adults: Placebo; Infants: Placebo; Toddlers: Placebo

Eligibility Criteria

• Age: 6 Weeks - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Healthy adults (≥ 18 and ≤ 45 years), toddlers (≥ 2 and ≤ 3 years), and infants (≥ 6 and ≤ 8 weeks)
• Participants will remain in the area during the study
• Females of childbearing potential must not be pregnant or breastfeeding, and willing to use adequate method of contraception during the trial.

You may not qualify if:

• Presence of fever or other acute illness
• concurrent participation in another clinical trial
• Presence of malnutrition or other systemic disorder.
• Infants with history of premature birth (\< 37 week gestational age)
• History of congenital abdominal disorders or surgery
• Suspected or known impairment of immune function
• Infants who have received rotavirus vaccine in the past
• Known sensitivity to any components of the vaccine
• History of anaphylactic reaction
• Major congenital or genetic defect
• Unwillingness to follow study schedule
• Receipt of immunoglobulin therapy or blood products in last 6 months
• History of chronic immunosuppressive medications (with the exception of inhaled or topical steroids)
• Any medical condition that, in the judgement of the investigator, would interfere with the protocol, or would interfere with participant's ability to adhere to the study protocol.
• Clinically significant screening laboratory value

Sponsors & Collaborators

• PATH: lead
• The Emmes Company, LLC: collaborator

Study Sites (3)

Respiratory and Meningeal Pathogens Research Unit (RMPRU)

Johannesburg, Gauteng, 2013, South Africa

Location

Shandukani Research Centre

Johannesburg, 2001, South Africa

Location

Family Clinical Research Unit (FAM-CRU) Stellenbosch Univ

Stellenbosch, 7505, South Africa

Location

Related Publications (1)

• Groome MJ, Fairlie L, Morrison J, Fix A, Koen A, Masenya M, Jose L, Madhi SA, Page N, McNeal M, Dally L, Cho I, Power M, Flores J, Cryz S. Safety and immunogenicity of a parenteral trivalent P2-VP8 subunit rotavirus vaccine: a multisite, randomised, double-blind, placebo-controlled trial. Lancet Infect Dis. 2020 Jul;20(7):851-863. doi: 10.1016/S1473-3099(20)30001-3. Epub 2020 Apr 3.

  PMID: 32251641 DERIVED

Results Point of Contact

• Title: Jorge Flores
• Organization: PATH

jeflores@path.org

(202) 822-0033

Study Officials

• Michelle Groom, MBBCh

  Chris Hani Baragwanath Hospital

  STUDY CHAIR

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: January 4, 2016
• First Posted: January 6, 2016
• Study Start: February 15, 2016
• Primary Completion: September 1, 2017
• Study Completion: December 22, 2017
• Last Updated: March 10, 2020
• Results First Posted: March 10, 2020

Record last verified: 2019-01

Data Sharing

• IPD Sharing: Will not share

Locations

ZA (3)