Safety and Immunogenicity of Two Intradermal Rabies Vaccine Regimens Administered With and Without Human Rabies Immunoglobulin in Subjects ≥ 1 Years of Age

NCT02177032 | Completed Phase 3 Results

• 2 other identifiers: V49_302013-CT0191
• Study Type: interventional
• Target: 885
• Locations: 2 countries
• Sites: 6

Brief Summary

Demonstrate non-inferiority of the immune response between new versus the currently recommended intradermal regimens of rabies vaccine when administered with or without rabies immunoglobulins in healthy subjects ≥ 1 years of age.

Conditions

Rabies Infection

Keywords

Rabies vaccines; intradermal; human rabies immunoglobulins

Outcome Measures

Primary Outcomes (1)

• Percentages of Subjects With RVNA Titer >= 0.5 and Vaccine Group Differences ("4-sites, 1-week" to That of "2-sites, TRC" ID PEP Regimen of the PCEC Rabies Vaccine With or Without HRIG Administration)

  Vaccine group differences are calculated assuming a binomial distribution and the associated confidence interval for the differences in percentage was based on M-N method. Non-inferiority of the immune response of the new "4-sites, 1-week" ID PEP regimen of the PCEC vaccine, with or without HRIG administration, to that of the currently recommended "2-sites, TRC" ID PEP regimen of the PCEC rabies vaccine with or without HRIG administration, as measured by the percentage of subjects with RVNA titer ≥ 0.5 IU/ml at day 50 in the whole study population.

  Study day 50 (D50)

Secondary Outcomes (11)

• Geometric Mean Rabies Virus Neutralizing Antibody (RVNA) Concentration and Between-group (2 ID Rabies Vaccine Regimens (4-sites, 1-week and 2-sites, TRC) With or Without HRIG) Ratio of GMCs

  Study Day 50

• Geometric Mean Rabies Virus Neutralizing Antibody Concentration at Days 8, 15, 91, 181 and 366 & Between-group (2 ID Rabies Vaccine Regimens (4-sites,1-week & 2-sites, TRC) With or Without HRIG) Ratio of GMCs in Children & Adult Subjects,≥ 1 Years of Age

  At Days 8, 15, 91, 181 and 366

• Percentages of Subjects With Anti-RVNA Titer ≥0.5 IU/mL at Days 8, 15, 91, 181 and 366 in Children and Adult Subjects and Vaccine Group Differences (2 ID Rabies Vaccine Regimens (4-sites, 1-week and 2-sites, TRC), With or Without HRIG), ≥ 1 Years of Age

  At Days 8, 15, 91, 181 and 366

• Geometric Mean Rabies Virus Neutralizing Antibody (RVNA) Concentration and Vaccine Group Differences in Adult Subjects, ≥ 18 Years of Age

  At Days 8, 15, 50, 91, 181 and 366

• Percentages of Subjects With Anti-RVNA Titer ≥0.5 IU/mL in Adult Subjects, ≥ 18 Years of Age

  At Days 8, 15,50, 91, 181 and 366

Study Arms (4)

4-sites, 1-week without HRIG

EXPERIMENTAL

PCEC rabies vaccine, administered ID according to the "4-sites, 1-week" regimen

Biological: Rabies vaccine

4-sites, 1-week with HRIG

EXPERIMENTAL

PCEC rabies vaccine, administered ID to adults, according to the "4-sites, 1-week" regimen plus HRIG

Biological: Rabies vaccines + Rabies immunoglobulins

2-sites, TRC without HRIG

ACTIVE COMPARATOR

PCEC rabies vaccine, administered ID according to the "2-sites, TRC" regimen

Biological: Rabies vaccine

2-sites, TRC with HRIG

ACTIVE COMPARATOR

PCEC rabies vaccine, administered ID to adults , according to the "2-sites, TRC" regimen plus HRIG

Biological: Rabies vaccines + Rabies immunoglobulins

Interventions

Rabies vaccine BIOLOGICAL

12 doses of the PCEC rabies vaccine, administered ID (0.1mL for each injection) according to the "4-sites, 1-week" regimen (i.e. 4 doses of vaccine; in both deltoids and anterolateral thigh areas, administered on days 1, 4, and 8).

4-sites, 1-week without HRIG

Rabies vaccines + Rabies immunoglobulins BIOLOGICAL

12 doses of the PCEC rabies vaccine, administered ID (0.1mL for each injection) to adults only, according to the "4-sites, 1-week" regimen (i.e. 4 doses of vaccine; in both deltoids and anterolateral thigh areas, administered on days 1, 4, and 8). HRIG will be administered on day 1 (before the first dose of the vaccine) in a dose of 20 IU/kg body weight intramuscularly into the gluteal muscle.

4-sites, 1-week with HRIG

Eligibility Criteria

• Age: 1 Year+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy males and females ≥ 1 years of age
• Individuals/ individual's parents or legal guardians who have given written consent
• Individuals in good health
• Individuals who can comply with study procedures

You may not qualify if:

• Behavioral or cognitive impairment or psychiatric disease.
• Unable to comprehend and to follow all required study procedures for the whole period of the study.
• History of illness or with an ongoing illness that may pose additional risk to the individual if he/she participates in the study.
• Individuals ≥ 1 to ≤ 17 years of age, who have or ever had a malignancy.
• Individuals ≥ 18 years of age, who have or who within the last 5 years, have had a malignancy (excluding nonmelanotic skin cancer) or lymphoproliferative disorder.
• Known or suspected impairment of the immune system (including but not limited to HIV, autoimmune disorders, immunosuppressive therapy as applicable).
• Female of childbearing potential who has not used any of the "acceptable contraceptive methods" for at least 2 months prior to study entry.
• Female of childbearing potential, refusal to use an "acceptable birth control method" through day 50.
• Female of childbearing potential, with a positive pregnancy test prior to enrollment.
• Received blood, blood products and/or plasma derivatives or any parenteral immunoglobulin preparation in the previous 12 weeks.
• Allergic to any of the vaccine components.
• Allergic to any of the human rabies immunoglobulin components.
• Contraindication or precaution against rabies vaccination.
• Contraindication or precaution against man rabies immunoglobulin administration.
• Planning to receive anti-malaria medications (e.g. Mefloquine) 14 days prior to day 1 vaccination through day 50.

Sponsors & Collaborators

• Novartis: lead
• Novartis Vaccines: collaborator

Study Sites (6)

4, De La Salle Health Sciences Institute

Cavite, 4114, Philippines

Location

1, Research Institute for Tropical Medicine

City of Muntinlupa, 1781, Philippines

Location

2, Asian Hospital and Medical Center

City of Muntinlupa, 1781, Philippines

Location

3, Research Institute for Tropical Medicine

City of Muntinlupa, Philippines

Location

11, Infectious Diseases Unit, Department of Pediatrics, Phramongkutklao hospital

Bangkok, Bangkok, 10400, Thailand

Location

12, Department of Tropical Pediatrics, Faculty of Tropical Medicine, Mahidol University

Bangkok, Bangkok, 10400, Thailand

Location

MeSH Terms

Interventions

Rabies Vaccines

Intervention Hierarchy (Ancestors)

Viral Vaccines; Vaccines; Biological Products; Complex Mixtures

Results Point of Contact

• Title: Posting Director
• Organization: Novartis Vaccines

RegistryContactVaccinesUS@novartis.com

Study Officials

• Novartis Vaccines

  Novartis Vaccines

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 24, 2014
• First Posted: June 27, 2014
• Study Start: June 1, 2014
• Primary Completion: October 1, 2014
• Study Completion: August 1, 2015
• Last Updated: April 7, 2017
• Results First Posted: April 7, 2017

Record last verified: 2017-02

Locations

TH (2); PH (4)