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

Primary Purpose

Rabies Infection

Status

Completed

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

Rabies vaccine

Rabies vaccines + Rabies immunoglobulins

Rabies vaccine

Rabies vaccines + Rabies immunoglobulins

About this trial

This is an interventional prevention trial for Rabies Infection focused on measuring Rabies vaccines, intradermal, human rabies immunoglobulins

Eligibility Criteria

1 Year - undefined (Child, Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

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

Exclusion Criteria:

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.

Sites / Locations

4, De La Salle Health Sciences Institute
1, Research Institute for Tropical Medicine
2, Asian Hospital and Medical Center
3, Research Institute for Tropical Medicine
11, Infectious Diseases Unit, Department of Pediatrics, Phramongkutklao hospital
12, Department of Tropical Pediatrics, Faculty of Tropical Medicine, Mahidol University

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Active Comparator

Arm Label

4-sites, 1-week without HRIG

4-sites, 1-week with HRIG

2-sites, TRC without HRIG

2-sites, TRC with HRIG

Arm Description

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

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

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

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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

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

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 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

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.

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

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)

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

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 Adult Subjects, ≥ 18 Years of Age. Percentage of subjects 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 in Children and Adult Subjects, ≥ 1 Years of Age

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

Percentages of Subjects With Anti-RVNA Titer ≥0.5 IU/mL in Children and Adult Subjects, ≥ 1 Years of Age

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

Number of Subjects Who Reported Solicited Local and Systemic Adverse Events After Any Vaccination

Number of subjects Who Reported Solicited Local and Systemic Adverse Events After Any Vaccination

Number of Subjects Reporting Unsolicited Adverse Events (AEs)

Safety was assessed in terms of the Number of Subjects Reporting Unsolicited Adverse Events (AEs)

Geometric Mean Rabies Virus Neutralizing Antibody (RVNA) Concentration ≥0.5 IU/mL and Vaccine Group Differences in Adult Subjects, ≥ 18 Years of Age

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

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

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

Full Information

NCT ID

NCT02177032

First Posted

June 24, 2014

Last Updated

February 21, 2017

Sponsor

Novartis

Collaborators

Novartis Vaccines

1. Study Identification

Unique Protocol Identification Number

NCT02177032

Brief Title

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

2. Study Status

Record Verification Date

February 2017

Overall Recruitment Status

Completed

Study Start Date

June 2014 (undefined)

Primary Completion Date

October 2014 (Actual)

Study Completion Date

August 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Novartis

Collaborators

Novartis Vaccines

4. Oversight

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Rabies Infection

Keywords

Rabies vaccines, intradermal, human rabies immunoglobulins

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

885 (Actual)

8. Arms, Groups, and Interventions

Arm Title

4-sites, 1-week without HRIG

Arm Type

Experimental

Arm Description

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

Arm Title

4-sites, 1-week with HRIG

Arm Type

Experimental

Arm Description

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

Arm Title

2-sites, TRC without HRIG

Arm Type

Active Comparator

Arm Description

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

Arm Title

2-sites, TRC with HRIG

Arm Type

Active Comparator

Arm Description

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

Intervention Type

Biological

Intervention Name(s)

Rabies vaccine

Intervention Description

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).

Intervention Type

Biological

Intervention Name(s)

Rabies vaccines + Rabies immunoglobulins

Intervention Description

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.

Intervention Type

Biological

Intervention Name(s)

Rabies vaccine

Intervention Description

8 doses of the PCEC rabies vaccine, administered ID (0.1ml for each injection) according to the "2-sites, TRC", updated Thai Red Cross regimen (i.e. 2 doses of vaccine; in both deltoids, administered on days 1, 4, 8, and 29).

Intervention Type

Biological

Intervention Name(s)

Rabies vaccines + Rabies immunoglobulins

Intervention Description

8 doses of the PCEC rabies vaccine, administered ID (0.1ml for each injection) to adults only, according to the "2-sites, TRC", updated Thai Red Cross regimen (i.e. 2 doses of vaccine; in both deltoids, administered on days 1, 4, 8, and 29). 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.

Primary Outcome Measure Information:

Title

Description

Time Frame

Study day 50 (D50)

Secondary Outcome Measure Information:

Title

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

Description

Time Frame

Study Day 50

Title

Description

Time Frame

At Days 8, 15, 91, 181 and 366

Title

Description

Time Frame

At Days 8, 15, 91, 181 and 366

Title

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

Description

Time Frame

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

Title

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

Description

Time Frame

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

Title

Geometric Mean Rabies Virus Neutralizing Antibody (RVNA) Concentration in Children and Adult Subjects, ≥ 1 Years of Age

Description

Time Frame

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

Title

Percentages of Subjects With Anti-RVNA Titer ≥0.5 IU/mL in Children and Adult Subjects, ≥ 1 Years of Age

Description

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

Time Frame

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

Title

Number of Subjects Who Reported Solicited Local and Systemic Adverse Events After Any Vaccination

Description

Number of subjects Who Reported Solicited Local and Systemic Adverse Events After Any Vaccination

Time Frame

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)

Title

Number of Subjects Reporting Unsolicited Adverse Events (AEs)

Description

Safety was assessed in terms of the Number of Subjects Reporting Unsolicited Adverse Events (AEs)

Time Frame

Day 1 to Day 366

Title

Geometric Mean Rabies Virus Neutralizing Antibody (RVNA) Concentration ≥0.5 IU/mL and Vaccine Group Differences in Adult Subjects, ≥ 18 Years of Age

Description

Time Frame

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

Title

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

Description

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

Time Frame

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

10. Eligibility

Sex

All

Minimum Age & Unit of Time

1 Year

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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 Exclusion Criteria: 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Novartis Vaccines

Organizational Affiliation

Novartis Vaccines

Official's Role

Study Chair

Facility Information:

Facility Name

4, De La Salle Health Sciences Institute

City

Cavite

ZIP/Postal Code

4114

Country

Philippines

Facility Name

1, Research Institute for Tropical Medicine

City

Muntinlupa

ZIP/Postal Code

1781

Country

Philippines

Facility Name

2, Asian Hospital and Medical Center

City

Muntinlupa

ZIP/Postal Code

1781

Country

Philippines

Facility Name

3, Research Institute for Tropical Medicine

City

Muntinlupa

Country

Philippines

Facility Name

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

City

Bangkok

ZIP/Postal Code

10400

Country

Thailand

Facility Name

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

City

Bangkok

ZIP/Postal Code

10400

Country

Thailand

12. IPD Sharing Statement

Learn more about this trial

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

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