Clinical trial NCT02177032: Safety and Immunogenicity of Two Intradermal Rabies Vaccine Regimens Administered With and Without Human Rabies Immunoglobulin in Subjects ≥ 1 Years of Age
Official title: Phase 3, Randomized, Stratified, Open Label, Multicenter, Controlled Clinical Study to Evaluate Safety and Immunogenicity of a Rabies Vaccine Administered, With and Without Human Rabies Immunoglobulin, Using the New "4-sites, 1-week" Intradermal Regimen for Postexposure Prophylaxis Compared to the Currently Recommended "2-sites, TRC" Intradermal Regimen in Children and Adults Subjects.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Rabies Infection
Keywords: Rabies vaccines
intradermal
human rabies immunoglobulins
Lead sponsor: Novartis
Sponsor class: INDUSTRY
Collaborators: name: Novartis Vaccines
First posted: 2014-06-27
Enrollment: 885
Sex: ALL
Minimum age (years): 1
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.


Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

1. Behavioral or cognitive impairment or psychiatric disease.
2. Unable to comprehend and to follow all required study procedures for the whole period of the study.
3. History of illness or with an ongoing illness that may pose additional risk to the individual if he/she participates in the study.
4. Individuals ≥ 1 to ≤ 17 years of age, who have or ever had a malignancy.
5. 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.
6. Known or suspected impairment of the immune system (including but not limited to HIV, autoimmune disorders, immunosuppressive therapy as applicable).
7. Female of childbearing potential who has not used any of the "acceptable contraceptive methods" for at least 2 months prior to study entry.
8. Female of childbearing potential, refusal to use an "acceptable birth control method" through day 50.
9. Female of childbearing potential, with a positive pregnancy test prior to enrollment.
10. Received blood, blood products and/or plasma derivatives or any parenteral immunoglobulin preparation in the previous 12 weeks.
11. Allergic to any of the vaccine components.
12. Allergic to any of the human rabies immunoglobulin components.
13. Contraindication or precaution against rabies vaccination.
14. Contraindication or precaution against man rabies immunoglobulin administration.
15. Planning to receive anti-malaria medications (e.g. Mefloquine) 14 days prior to day 1 vaccination through day 50.
16. Participating in any clinical trial with another investigational product 30 days prior to first study visit or intent to participate in another clinical study at any time during the conduct of this study.
17. Received any other vaccines within 14 days (for inactivated vaccines) or 28 days (for live vaccines) prior to enrollment in this study or who are planning to receive any vaccine within 28 days from the study vaccines.
18. Body temperature ≥ 38.0°C (≥ 100.4°F) within 3 days of intended study vaccination.
19. Received rabies vaccines or rabies immunoglobulin or have been exposed to rabies.
20. Part of the study personnel or immediate family members of study personnel conducting this study.
21. Current or history of drug or alcohol abuse within the past 2 years.

Primary outcomes:
measure: 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)
timeFrame: Study day 50 (D50)
Secondary outcomes:
measure: 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
timeFrame: Study Day 50
measure: 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
timeFrame: At Days 8, 15, 91, 181 and 366
measure: 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
timeFrame: At Days 8, 15, 91, 181 and 366
measure: Geometric Mean Rabies Virus Neutralizing Antibody (RVNA) Concentration and Vaccine Group Differences in Adult Subjects, ≥ 18 Years of Age
timeFrame: At Days 8, 15, 50, 91, 181 and 366
measure: Percentages of Subjects With Anti-RVNA Titer ≥0.5 IU/mL in Adult Subjects, ≥ 18 Years of Age
timeFrame: At Days 8, 15,50, 91, 181 and 366
measure: Geometric Mean Rabies Virus Neutralizing Antibody (RVNA) Concentration in Children and Adult Subjects, ≥ 1 Years of Age
timeFrame: At Days 8, 15, 50, 91, 181 and 366
measure: Percentages of Subjects With Anti-RVNA Titer ≥0.5 IU/mL in Children and Adult Subjects, ≥ 1 Years of Age
timeFrame: At Days 8, 15, 50, 91, 181 and 366
measure: Number of Subjects Who Reported Solicited Local and Systemic Adverse Events After Any Vaccination
timeFrame: From day 1 to day 3; from day 4 to day 7; from day 8 to day 14; from day 29 to day 35(2-sites, TRC PEP, ID regimen)
measure: Number of Subjects Reporting Unsolicited Adverse Events (AEs)
timeFrame: Day 1 to Day 366
measure: Geometric Mean Rabies Virus Neutralizing Antibody (RVNA) Concentration ≥0.5 IU/mL and Vaccine Group Differences in Adult Subjects, ≥ 18 Years of Age
timeFrame: At Days 8, 15, 50, 91, 181 and 366
measure: Percentages of Subjects With Anti-RVNA Titer ≥0.5 IU/mL in Adult Subjects, ≥ 18 Years of Age
timeFrame: At Days 8, 15,50, 91, 181 and 366
Other outcomes:
Locations:
city: Cavite
country: Philippines
facility: 4, De La Salle Health Sciences Institute
city: Muntinlupa
country: Philippines
facility: 1, Research Institute for Tropical Medicine
city: Muntinlupa
country: Philippines
facility: 2, Asian Hospital and Medical Center
city: Muntinlupa
country: Philippines
facility: 3, Research Institute for Tropical Medicine
city: Bangkok
country: Thailand
facility: 11, Infectious Diseases Unit, Department of Pediatrics, Phramongkutklao hospital
city: Bangkok
country: Thailand
facility: 12, Department of Tropical Pediatrics, Faculty of Tropical Medicine, Mahidol University
Study officials:
affiliation: Novartis Vaccines
name: Novartis Vaccines
role: STUDY_CHAIR
References: