Safety and Immunogenicity of Two Intradermal Rabies Vaccine Regimens Administered With and Without Human Rabies Immunoglobulin in Subjects ≥ 1 Years of Age
- Conditions
- Rabies Infection
- Interventions
- Biological: Rabies vaccineBiological: Rabies vaccines + Rabies immunoglobulins
- Registration Number
- NCT02177032
- Lead Sponsor
- Novartis
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 885
- 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
- 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.
- 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.
- 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.
- Body temperature ≥ 38.0°C (≥ 100.4°F) within 3 days of intended study vaccination.
- Received rabies vaccines or rabies immunoglobulin or have been exposed to rabies.
- Part of the study personnel or immediate family members of study personnel conducting this study.
- Current or history of drug or alcohol abuse within the past 2 years.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description 4-sites, 1-week without HRIG Rabies vaccine PCEC rabies vaccine, administered ID according to the "4-sites, 1-week" regimen 2-sites, TRC with HRIG Rabies vaccines + Rabies immunoglobulins PCEC rabies vaccine, administered ID to adults , according to the "2-sites, TRC" regimen plus HRIG 2-sites, TRC without HRIG Rabies vaccine PCEC rabies vaccine, administered ID according to the "2-sites, TRC" regimen 4-sites, 1-week with HRIG Rabies vaccines + Rabies immunoglobulins PCEC rabies vaccine, administered ID to adults, according to the "4-sites, 1-week" regimen plus HRIG
- Primary Outcome Measures
Name Time Method 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) Study day 50 (D50) 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.
- Secondary Outcome Measures
Name Time Method Number of Subjects Who Reported Solicited Local and Systemic Adverse Events After Any Vaccination 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) Number of subjects Who Reported Solicited Local and Systemic Adverse Events After Any Vaccination
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 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.
RVNA percentage of subjects with RVNA titer ≥ 0.5 IU/mL at study days 8, 15, 91, 181, and 366 following administration of the 2 ID rabies vaccine regimens (4-sites, 1-week and 2-sites, TRC), with or without HRIG, in the whole study population.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 Immunogenicity was assessed in terms of the number of subjects With Anti-RVNA concentration ≥0.5 IU/mL at Days 8, 15, 50, 91, 181 and 366 in Adult Subjects, ≥ 18 Years of Age
Geometric Mean Rabies Virus Neutralizing Antibody (RVNA) Concentration in Children and Adult Subjects, ≥ 1 Years of Age At Days 8, 15, 50, 91, 181 and 366 Immunogenicity was assessed in terms of the Geometric Mean Rabies Virus Neutralizing Antibody (RVNA) Concentration at Days 8, 15, 50, 91, 181 and 366 in Children and Adult Subjects, ≥ 1 Years of Age
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 Immunogenicity was assessed in terms of the Geometric Mean Rabies Virus Neutralizing Antibody (RVNA) Concentration at Days 8, 15, 50,91, 181 and 366 in Adult Subjects, ≥ 18 Years of Age.
RVNA GMCs with RVNA titer ≥ 0.5 IU/mL at days 8, 15, 50, 91, 181 and 366 and group differences (4-sites,1-week without HRIG versus 4-sites,1-week with HRIG; 4-sites,1-week with HRIG versus 2-sites,TRC with HRIG; 4-sites,1-week without HRIG versus 2-sites, TRC without HRIG)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 Immunogenicity was assessed in terms of Geometric Mean Rabies Virus Neutralizing Antibody (RVNA) Concentration in Children and Adult Subjects, ≥ 1 Years of Age at day 50 The GMCs, GMRs (i.e., within group ratio) and associated two sided 95% confidence intervals for each group were computed by exponentiating (base 10) of the least square means of the logarithmically transformed (base 10) concentration (and their differences) and the 95% CIs obtained from an Analysis of variance (ANOVA) with vaccine regimen, age strata and center as factors.
Non-inferiority of the immune response between the 2 ID rabies vaccine regimens (4-sites, 1-week and 2-sites, TRC) with or without HRIG administration as measured by RVNA GMCs at day 50 in the whole study population.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 Immunogenicity was assessed in terms of the Geometric Mean Rabies Virus Neutralizing Antibody (RVNA) Concentration at Days 8, 15, 91, 181 and 366 in Children and Adult Subjects, ≥ 1 Years of Age The GMCs, GMRs (i.e., within group ratio) and associated two sided 95% confidence intervals for each group were computed by exponentiating (base 10) of the least square means of the logarithmically transformed (base 10) concentration (and their differences) and the 95% CIs obtained from an Analysis of variance (ANOVA) with vaccine regimen, age strata and center as factors.
Non-inferiority of the immune response between the 2 ID rabies vaccine regimens (4-sites, 1-week and 2-sites, TRC) with or without HRIG administration as measured by RVNA GMCs at day 50 in the whole study population.Percentages of Subjects With Anti-RVNA Titer ≥0.5 IU/mL in Children and Adult Subjects, ≥ 1 Years of Age At Days 8, 15, 50, 91, 181 and 366 Immunogenicity was assessed in terms of the Percentages of Subjects With Anti-RVNA concentration ≥0.5 IU/mL at Days 8, 15, 50, 91, 181 and 366 in Children and Adult Subjects, ≥ 1 Years of Age
Geometric Mean Rabies Virus Neutralizing Antibody (RVNA) Concentration ≥0.5 IU/mL and Vaccine Group Differences in Adult Subjects, ≥ 18 Years of Age At Days 8, 15, 50, 91, 181 and 366 Immunogenicity was assessed in terms of the Geometric Mean Rabies Virus Neutralizing Antibody (RVNA) Concentration ≥0.5 IU/mL at Days 8, 15, 50,91, 181 and 366 in Adult Subjects, ≥ 18 Years of Age
Number of Subjects Reporting Unsolicited Adverse Events (AEs) Day 1 to Day 366 Safety was assessed in terms of the Number of Subjects Reporting Unsolicited Adverse Events (AEs)
Trial Locations
- Locations (6)
1, Research Institute for Tropical Medicine
🇵🇭Muntinlupa, Philippines
2, Asian Hospital and Medical Center
🇵🇭Muntinlupa, Philippines
4, De La Salle Health Sciences Institute
🇵🇭Cavite, Philippines
3, Research Institute for Tropical Medicine
🇵🇭Muntinlupa, Philippines
11, Infectious Diseases Unit, Department of Pediatrics, Phramongkutklao hospital
🇹🇭Bangkok, Thailand
12, Department of Tropical Pediatrics, Faculty of Tropical Medicine, Mahidol University
🇹🇭Bangkok, Thailand