Back to resultsA Study to Evaluate the Safety and Immunogenicity of GlaxoSmithKline (GSK) Biologicals' Experimental Rabies Vaccine in Healthy Adults
Primary Purpose
Virus Diseases
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Low dose formulation of RG SAM (CNE) vaccine (GSK3903133A)
Medium dose formulation of RG SAM (CNE) vaccine (GSK3903133A)
Lower dose formulation of RG SAM (CNE) vaccine (GSK3903133A)
Lowest dose formulation of RG SAM (CNE) vaccine (GSK3903133A)
Saline Placebo
RabAvert
Sponsored by
About this trial
This is an interventional prevention trial for Virus Diseases focused on measuring First Time in Human, Vaccine, Healthy subjects, Rabies
Eligibility Criteria
Inclusion Criteria:
- Participants who, in the opinion of the investigator, can and will comply with the requirements of the protocol (e.g. participation in genetics research, completion of the electronic diary cards, return for follow-up visits).
- Written informed consent obtained from the participant prior to performance of any study specific procedure.
- Healthy participants as established by medical history and clinical examination before entering into the study.
- A male or female participant between, and including, 18 and 40 years of age at the time of the first vaccination.
- Body Mass Index >18 Kg/m^2 and <35 Kg/m^2.
Participants with following hematological/biochemical parameters:
- White Blood Cells and differential, within the study designated laboratory normal range. Participants with FDA toxicity grade 1 differential cell counts and considered not clinically significant may be enrolled at the discretion of the investigator, and with the review and approval of the medical monitor.
- Platelets = 125,000 - 500,000 cells/mm^3
- Hemoglobin within normal range of the study designated laboratory
- Alanine aminotransferase within the study designated laboratory normal range
- Aspartate aminotransferase within the study designated laboratory normal range
- Total bilirubin within the study designated laboratory normal range
- Alkaline phosphatase within the study designated laboratory normal range
- Serum creatinine less than or equal to 1.1 times study designated laboratory's upper normal limit .
- Seronegative for hepatitis B surface antigen, hepatitis C virus antibodies, or human immunodeficiency virus antibodies
- Female participants of non-childbearing potential may be enrolled in the study. Non-childbearing potential is defined as pre-menarche, current bilateral tubal ligation or occlusion, hysterectomy, bilateral ovariectomy or post-menopause.
Female participants of childbearing potential may be enrolled in the study, if the participant
- has practiced adequate contraception for 30 days prior to vaccination, and
- has a negative pregnancy test on the day of vaccination, and
- has agreed to continue adequate contraception during the entire treatment period and for 2 months after completion of the vaccination series
Exclusion Criteria:
- History of diagnosis with rabies exposure, infection or disease.
- Any confirmed or suspected immunosuppressive or immunodeficient condition based on medical history and physical examination.
- Family history of congenital or hereditary immunodeficiency.
- History of or current autoimmune disease.
- History of any reaction or hypersensitivity likely to be exacerbated by any components of RabAvert including polygeline, bovine gelatin, neomycin, chlortetracycline and amphotericin B, chicken protein, egg products or any other vaccine component.
- Lymphoproliferative disorder or malignancy within previous 5 years (excluding effectively treated non-melanotic skin cancer).
- Hypersensitivity to latex.
- History of Type I hypersensitivity reactions to any beta-lactam antibiotics (penicillin, aminopenicillins, cephalosporins and carbapenems).
- Any acute or chronic, clinically significant disease, as determined by physical examination, laboratory screening tests, subject personal report and/or General Physician (GP) information.
- Use of any investigational or non-registered product other than the study vaccines during the period starting 30 days before the first dose of study vaccines, or planned use during the study period.
- Planned administration/administration of a vaccine not foreseen by the study protocol in the period starting 30 days before the vaccination and ending 30 days after (Influenza vaccine excluded).
- Previous vaccination with any licensed or investigational rabies vaccine.
- Administration of immunoglobulins and/or any blood products within the 3 months preceding the dose of study vaccine or planned administration during the study period.
- Chronic administration (defined as more than 14 days in total) of immunosuppressants or other immune-modifying drugs during the period within 6 months prior to the vaccine dose.
- Current allergy treatment with allergen immunotherapy with antigen injections, unless on maintenance schedule.
- Concomitant or planned administration of antimalarial drugs, to include hydroxychloroquine within 30 days of vaccination.
- Current anti-tuberculosis prophylaxis or therapy.
- Concurrently participating in another clinical study, at any time during the study period, in which the participant has been/will be exposed to an investigational or a non-investigational vaccine/product.
- Pregnant or lactating female participant.
- Female participant planning to become pregnant or planning to discontinue contraceptive precautions.
- Participants at a higher risk than the average US resident with regard to exposure to rabies, per the RabAvert package insert and rabies vaccination recommendations from the Centers for Disease Control (CDC).
- Participants with extensive tattoos covering deltoid region on both the arms that would preclude the assessment of local reactogenicity.
- Planned move to a location that will prohibit participating in the trial until study end.
- Any medical, psychiatric, social condition, occupational reason or other responsibility that, in the judgment of the investigator, is a contraindication to protocol participation.
Sites / Locations
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm Type
Experimental
Experimental
Experimental
Experimental
Placebo Comparator
Active Comparator
Arm Label
Low dose (Ld-) RG SAM (CNE) group
Medium dose (Md-) RG SAM (CNE) group
Lower dose (Lrd-) RG SAM (CNE) group
Lowest dose (Ltd-) RG SAM (CNE) group
Saline Placebo group
RabAvert group
Arm Description
In Part 1 of the study, healthy adults, 18 to 40 years of age, will receive one intramuscular injection of RG SAM (CNE) low dose formulation vaccine in one arm and one intramuscular injection of saline solution in the opposite arm at Days 1 and 61). In Part 2 of the study, healthy adults, 18 to 40 years of age, will receive one intramuscular injection of RG SAM (CNE) low dose formulation vaccine in one arm according to a 0, 2, 6-month schedule (i.e. at Days 1 and 61)
Healthy adults,18 to 40 years of age, will receive one intramuscular injection of RG SAM (CNE) medium dose formulation vaccine in one arm and one intramuscular injection of saline solution in the opposite arm at Day 1.
Healthy adults, 18 to 40 years of age, will receive one intramuscular injection of RG SAM (CNE) lower dose formulation vaccine in one arm according to a 0, 2, 6-month schedule (i.e. at Days 1 and 61)
Healthy adults, 18 to 40 years of age, will receive one intramuscular injection of RG SAM (CNE) lowest dose formulation vaccine in one arm according to a 0, 2, 6-month schedule (i.e. at Days 1 and 61)
In Part 1 of the study, healthy adults, 18 to 40 years of age, will receive two intramuscular injections of saline placebo, one in each arm, according to a 0, 2, 6-month schedule (i.e. at Days 1 and 61). In Part 2 of the study, healthy adults, 18 to 40 years of age will receive one intramuscular injections of saline placebo in one arm according to a 0, 2, 6-month schedule (i.e. at Days 1 and 61).
In Part 1 of the study, healthy adults, 18 to 40 years of age, will receive one intramuscular injection of RabAvert in one arm and one intramuscular injection of saline solution in the other arm, according to a 0, 2, 6-month schedule (i.e. at Days 1 and 61). In Part 2 of the study, healthy adults, 18 to 40 years of age, will receive one intramuscular injection of RabAvert in one arm according to a 0, 2, 6-month schedule (i.e. at Days 1 and 61).
Outcomes
Primary Outcome Measures
Number of participants reporting solicited local adverse events (AEs) during the 7-day follow-up period after the first dose received in the Primary vaccination phase
The following local AEs are solicited: pain, redness and swelling at injection site.
Number of participants reporting solicited local adverse events (AEs) during the 7-day follow-up period after the second dose received in the Primary vaccination phase
The following local AEs are solicited: pain, redness and swelling at injection site.
Number of participants reporting solicited general AEs during the 7-day follow-up period after the first dose received in the Primary vaccination phase
The following general AEs are solicited: fatigue, fever, nausea, vomiting, diarrhea, abdominal pain and headache.
Fever is defined as temperature ≥ 38.0°C / 100.4°F. The preferred location for measuring temperature in this study is the oral cavity.
Number of participants reporting solicited general AEs during the 7-day follow-up period after the second dose received in the Primary vaccination phase
The following general AEs are solicited: fatigue, fever, nausea, vomiting, diarrhea, abdominal pain and headache.
Fever is defined as temperature ≥ 38.0°C / 100.4°F. The preferred location for measuring temperature in this study is the oral cavity.
Number of participants reporting unsolicited AEs during a 30-day follow-up period follow-up after the first dose received in the Primary vaccination phase
Unsolicited AE is defined as an AE reported in addition to those solicited during the clinical study and as any solicited AE with onset outside the specified period of follow-up for solicited symptoms.
Number of participants reporting unsolicited AEs during a 30-day follow-up period follow-up after the second dose received in the Primary vaccination phase
Unsolicited AE is defined as an AE reported in addition to those solicited during the clinical study and as any solicited AE with onset outside the specified period of follow-up for solicited symptoms.
Number of participants with hematological and biochemical laboratory abnormalities at Day 1.
Clinically significant abnormal laboratory findings (e.g. clinical chemistry and hematology) are reported. The investigator exercises his or her medical and scientific judgement in deciding whether an abnormal laboratory finding or other abnormal assessment is clinically significant.
Number of participants with hematological and biochemical laboratory abnormalities at Day 4.
Clinically significant abnormal laboratory findings (e.g. clinical chemistry and hematology) are reported. The investigator exercises his or her medical and scientific judgement in deciding whether an abnormal laboratory finding or other abnormal assessment is clinically significant.
Number of participants with hematological and biochemical laboratory abnormalities at Day 8.
Clinically significant abnormal laboratory findings (e.g. clinical chemistry and hematology) are reported. The investigator exercises his or her medical and scientific judgement in deciding whether an abnormal laboratory finding or other abnormal assessment is clinically significant.
Number of participants with hematological and biochemical laboratory abnormalities at Day 61.
Clinically significant abnormal laboratory findings (e.g. clinical chemistry and hematology) are reported. The investigator exercises his or her medical and scientific judgement in deciding whether an abnormal laboratory finding or other abnormal assessment is clinically significant.
Number of participants with hematological and biochemical laboratory abnormalities at Day 64.
Clinically significant abnormal laboratory findings (e.g. clinical chemistry and hematology) are reported. The investigator exercises his or her medical and scientific judgement in deciding whether an abnormal laboratory finding or other abnormal assessment is clinically significant.
Number of participants with hematological and biochemical laboratory abnormalities at Day 68.
Clinically significant abnormal laboratory findings (e.g. clinical chemistry and hematology) are reported. The investigator exercises his or her medical and scientific judgement in deciding whether an abnormal laboratory finding or other abnormal assessment is clinically significant.
Number of participants reporting medically attended AE (MAEs)
A medically attended adverse event is an AE for which the participants received medical attention defined as hospitalization, an emergency room visit or a visit to or from medical personnel (i.e., nurse practitioner or physician assistant or medical doctor) for any reason.
Number of participants reporting serious adverse events (SAEs)
SAEs assessed include any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity or is a congenital anomaly/birth defect in the offspring of a study patient.
Number of participants reporting potential immune-mediated diseases (pIMDs)
pIMDs are a subset of AEs that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune etiology.
Secondary Outcome Measures
Number of participants reporting solicited local adverse events (AEs) during the 7-day follow-up period after each vaccination received from Day 1 up to study conclusion at Month 18
The following local AEs are solicited: pain, redness and swelling at injection site.
Number of participants reporting solicited general AEs during the 7-day follow-up period after each vaccination received from Day 1 up to study conclusion at Month 18
The following general AEs are solicited: fatigue, fever, nausea, vomiting, diarrhea, abdominal pain and headache.
Fever is defined as temperature ≥ 38.0°C / 100.4°F. The preferred location for measuring temperature in this study is the oral cavity.
Number of participants reporting unsolicited AEs during a 30-day follow-up period after each vaccination from Day 1 up to study conclusion at Month 18
Unsolicited AE is defined as an AE reported in addition to those solicited during the clinical study and as any solicited AE with onset outside the specified period of follow-up for solicited symptoms.
Number of participants with hematological and biochemical laboratory abnormalities at Day 1, Day 4, Day 8, Day 61, Day 64, Day 68, Day 181, Day 184 and Day 188
Clinically significant abnormal laboratory findings (e.g. clinical chemistry and hematology) are reported. The investigator exercises his or her medical and scientific judgement in deciding whether an abnormal laboratory finding or other abnormal assessment is clinically significant.
Number of participants reporting MAEs from Day 1 up to study conclusion at Month 14
A medically attended adverse event is an AE for which the participants received medical attention defined as hospitalization, an emergency room visit or a visit to or from medical personnel (i.e., nurse practitioner or physician assistant or medical doctor) for any reason.
Number of participants reporting SAEs from Day 1 up to study conclusion at Month 14
SAEs assessed include any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity or is a congenital anomaly/birth defect in the offspring of a study patient.
Number of participants reporting pIMDs from Day 1 up to study conclusion at Month 14
pIMDs are a subset of AEs that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune etiology.
Evaluation of immunogenicity in terms of Rabies Virus Neutralizing Antibody (RVNA) concentrations
RVNA concentrations determined by Rapid Fluorescence Foci Inhibition Test (RFFIT) are presented as geometric mean concentrations (GMCs), expressed in International Unit per milliliter (IU/mL).
Evaluation of immunogenicity in terms of Anti-rabies G IgG antibody concentrations
Anti-rabies G IgG antibody concentrations determined by Enzyme Linked Immunosorbent Assay (ELISA) are presented as GMCs, expressed in ELISA unit per milliliter (EU/mL).
Evaluation of persistence of immunogenicity in terms of anti-rabies G IgG antibody concentrations at 5 months after last vaccination
Anti-rabies G IgG antibody concentrations determined by ELISA are presented as GMCs, expressed in EU/mL.
Evaluation of persistence of immunogenicity in terms of anti-rabies G IgG antibody concentrations at 10 months after last vaccination
Anti-rabies G IgG antibody concentrations determined by ELISA are presented as GMCs, expressed in EU/mL.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04062669
Brief Title
A Study to Evaluate the Safety and Immunogenicity of GlaxoSmithKline (GSK) Biologicals' Experimental Rabies Vaccine in Healthy Adults
Official Title
Safety and Immunogenicity of GSK's Rabies G SAM (CNE) Vaccine [GSK3903133A] in Healthy Adults.
Study Type
Interventional
2. Study Status
Record Verification Date
January 2023
Overall Recruitment Status
Completed
Study Start Date
August 13, 2019 (Actual)
Primary Completion Date
July 28, 2021 (Actual)
Study Completion Date
July 1, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
GlaxoSmithKline
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this first time-in-human (FTiH) study is to evaluate the safety, reactogenicity and immunogenicity of different dose levels of an experimental rabies glycoprotein G (RG) vaccine (RG-SAM [CNE] vaccine), made using a new technology, when administered intramuscularly (IM) on a 0, 2, 6 *-month schedule to healthy adults.
* There will be no vaccinations with the third dose of any of the study treatments.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Virus Diseases
Keywords
First Time in Human, Vaccine, Healthy subjects, Rabies
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
In Part 1 of the study, only data during the primary vaccination phase (from study start to Day 91) will be collected in an observer-blind manner. By observer-blind, it is meant that the vaccines recipient and those responsible for the evaluation of any study endpoint will all be unaware of which vaccine was administered.
For Part 1, the study will be observer-blind until Day 91. When the Day 91 analysis will result in unblinding of all the subjects to the sponsor. Therefore, the study cannot be considered observer-blind beyond Day 91 and will be conducted in a single-blind* manner thereafter; with all subjects remaining blinded up to study conclusion (Month 14).
For Part 2, the study will be conducted in open-label manner from study start to study conclusion.
*Due to the recent COVID-19 pandemic, the study will be fully unblinded from study start to study conclusion to allow all subject treatments to be known to the team and investigators, thereby facilitating rapid safety assessment.
Allocation
Randomized
Enrollment
82 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Low dose (Ld-) RG SAM (CNE) group
Arm Type
Experimental
Arm Description
In Part 1 of the study, healthy adults, 18 to 40 years of age, will receive one intramuscular injection of RG SAM (CNE) low dose formulation vaccine in one arm and one intramuscular injection of saline solution in the opposite arm at Days 1 and 61).
In Part 2 of the study, healthy adults, 18 to 40 years of age, will receive one intramuscular injection of RG SAM (CNE) low dose formulation vaccine in one arm according to a 0, 2, 6-month schedule (i.e. at Days 1 and 61)
Arm Title
Medium dose (Md-) RG SAM (CNE) group
Arm Type
Experimental
Arm Description
Healthy adults,18 to 40 years of age, will receive one intramuscular injection of RG SAM (CNE) medium dose formulation vaccine in one arm and one intramuscular injection of saline solution in the opposite arm at Day 1.
Arm Title
Lower dose (Lrd-) RG SAM (CNE) group
Arm Type
Experimental
Arm Description
Healthy adults, 18 to 40 years of age, will receive one intramuscular injection of RG SAM (CNE) lower dose formulation vaccine in one arm according to a 0, 2, 6-month schedule (i.e. at Days 1 and 61)
Arm Title
Lowest dose (Ltd-) RG SAM (CNE) group
Arm Type
Experimental
Arm Description
Healthy adults, 18 to 40 years of age, will receive one intramuscular injection of RG SAM (CNE) lowest dose formulation vaccine in one arm according to a 0, 2, 6-month schedule (i.e. at Days 1 and 61)
Arm Title
Saline Placebo group
Arm Type
Placebo Comparator
Arm Description
In Part 1 of the study, healthy adults, 18 to 40 years of age, will receive two intramuscular injections of saline placebo, one in each arm, according to a 0, 2, 6-month schedule (i.e. at Days 1 and 61).
In Part 2 of the study, healthy adults, 18 to 40 years of age will receive one intramuscular injections of saline placebo in one arm according to a 0, 2, 6-month schedule (i.e. at Days 1 and 61).
Arm Title
RabAvert group
Arm Type
Active Comparator
Arm Description
In Part 1 of the study, healthy adults, 18 to 40 years of age, will receive one intramuscular injection of RabAvert in one arm and one intramuscular injection of saline solution in the other arm, according to a 0, 2, 6-month schedule (i.e. at Days 1 and 61).
In Part 2 of the study, healthy adults, 18 to 40 years of age, will receive one intramuscular injection of RabAvert in one arm according to a 0, 2, 6-month schedule (i.e. at Days 1 and 61).
Intervention Type
Biological
Intervention Name(s)
Low dose formulation of RG SAM (CNE) vaccine (GSK3903133A)
Intervention Description
Subjects in the low dose (Ld-) RG SAM (CNE) group will receive 2 doses of RG SAM (CNE) low dose formulation, administered intramuscularlyat Days 1 and 61.
Intervention Type
Biological
Intervention Name(s)
Medium dose formulation of RG SAM (CNE) vaccine (GSK3903133A)
Intervention Description
Subjects in the medium dose (Md-) RG SAM (CNE) group will receive 1 doses of RG SAM (CNE) medium dose formulation, administered intramuscularly at Day 1.
Intervention Type
Biological
Intervention Name(s)
Lower dose formulation of RG SAM (CNE) vaccine (GSK3903133A)
Intervention Description
Subjects in the Lower dose (Lrd-) RG SAM (CNE) group will receive 2 doses of RG SAM (CNE) lower dose formulation, administered intramuscularly, according to a 0, 2-month schedule (i.e. at Days 1 and 61)
Intervention Type
Biological
Intervention Name(s)
Lowest dose formulation of RG SAM (CNE) vaccine (GSK3903133A)
Intervention Description
Subjects in the Lowest dose (Ltd-) RG SAM (CNE) group will receive 2 doses of RG SAM (CNE) lowest dose formulation, administered intramuscularly, according to a 0, 2-month schedule (i.e. at Days 1 and 61)
Intervention Type
Drug
Intervention Name(s)
Saline Placebo
Intervention Description
Subjects in the Saline Placebo group will receive 2 doses of saline Placebo, administered intramuscularly Day 1 and 61.
Intervention Type
Biological
Intervention Name(s)
RabAvert
Intervention Description
Subjects in the RabAvert Group will receive 2 doses of RabAvert vaccine, administered intramuscularly, at Days 1 and 61.
Primary Outcome Measure Information:
Title
Number of participants reporting solicited local adverse events (AEs) during the 7-day follow-up period after the first dose received in the Primary vaccination phase
Description
The following local AEs are solicited: pain, redness and swelling at injection site.
Time Frame
During the 7-day follow-up period after the first dose (administered at Day 1)
Title
Number of participants reporting solicited local adverse events (AEs) during the 7-day follow-up period after the second dose received in the Primary vaccination phase
Description
The following local AEs are solicited: pain, redness and swelling at injection site.
Time Frame
During the 7-day follow-up period after the second dose (administered at Day 61)
Title
Number of participants reporting solicited general AEs during the 7-day follow-up period after the first dose received in the Primary vaccination phase
Description
The following general AEs are solicited: fatigue, fever, nausea, vomiting, diarrhea, abdominal pain and headache.
Fever is defined as temperature ≥ 38.0°C / 100.4°F. The preferred location for measuring temperature in this study is the oral cavity.
Time Frame
During the 7-day follow-up period after the first dose (administered at Day 1)
Title
Number of participants reporting solicited general AEs during the 7-day follow-up period after the second dose received in the Primary vaccination phase
Description
The following general AEs are solicited: fatigue, fever, nausea, vomiting, diarrhea, abdominal pain and headache.
Fever is defined as temperature ≥ 38.0°C / 100.4°F. The preferred location for measuring temperature in this study is the oral cavity.
Time Frame
During the 7-day follow-up period after the second dose (administered at Day 61)
Title
Number of participants reporting unsolicited AEs during a 30-day follow-up period follow-up after the first dose received in the Primary vaccination phase
Description
Unsolicited AE is defined as an AE reported in addition to those solicited during the clinical study and as any solicited AE with onset outside the specified period of follow-up for solicited symptoms.
Time Frame
During the 30-day follow-up period after the first dose (administered at Day 1).
Title
Number of participants reporting unsolicited AEs during a 30-day follow-up period follow-up after the second dose received in the Primary vaccination phase
Description
Unsolicited AE is defined as an AE reported in addition to those solicited during the clinical study and as any solicited AE with onset outside the specified period of follow-up for solicited symptoms.
Time Frame
During the 30-day follow-up period after the second dose (administered at Day 61).
Title
Number of participants with hematological and biochemical laboratory abnormalities at Day 1.
Description
Clinically significant abnormal laboratory findings (e.g. clinical chemistry and hematology) are reported. The investigator exercises his or her medical and scientific judgement in deciding whether an abnormal laboratory finding or other abnormal assessment is clinically significant.
Time Frame
At Day 1
Title
Number of participants with hematological and biochemical laboratory abnormalities at Day 4.
Description
Clinically significant abnormal laboratory findings (e.g. clinical chemistry and hematology) are reported. The investigator exercises his or her medical and scientific judgement in deciding whether an abnormal laboratory finding or other abnormal assessment is clinically significant.
Time Frame
At Day 4.
Title
Number of participants with hematological and biochemical laboratory abnormalities at Day 8.
Description
Clinically significant abnormal laboratory findings (e.g. clinical chemistry and hematology) are reported. The investigator exercises his or her medical and scientific judgement in deciding whether an abnormal laboratory finding or other abnormal assessment is clinically significant.
Time Frame
At Day 8.
Title
Number of participants with hematological and biochemical laboratory abnormalities at Day 61.
Description
Clinically significant abnormal laboratory findings (e.g. clinical chemistry and hematology) are reported. The investigator exercises his or her medical and scientific judgement in deciding whether an abnormal laboratory finding or other abnormal assessment is clinically significant.
Time Frame
At Day 61.
Title
Number of participants with hematological and biochemical laboratory abnormalities at Day 64.
Description
Clinically significant abnormal laboratory findings (e.g. clinical chemistry and hematology) are reported. The investigator exercises his or her medical and scientific judgement in deciding whether an abnormal laboratory finding or other abnormal assessment is clinically significant.
Time Frame
At Day 64.
Title
Number of participants with hematological and biochemical laboratory abnormalities at Day 68.
Description
Clinically significant abnormal laboratory findings (e.g. clinical chemistry and hematology) are reported. The investigator exercises his or her medical and scientific judgement in deciding whether an abnormal laboratory finding or other abnormal assessment is clinically significant.
Time Frame
At Day 68.
Title
Number of participants reporting medically attended AE (MAEs)
Description
A medically attended adverse event is an AE for which the participants received medical attention defined as hospitalization, an emergency room visit or a visit to or from medical personnel (i.e., nurse practitioner or physician assistant or medical doctor) for any reason.
Time Frame
During 90 days (from Day 1 to Day 91)
Title
Number of participants reporting serious adverse events (SAEs)
Description
SAEs assessed include any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity or is a congenital anomaly/birth defect in the offspring of a study patient.
Time Frame
During 90 days (from Day 1 to Day 91)
Title
Number of participants reporting potential immune-mediated diseases (pIMDs)
Description
pIMDs are a subset of AEs that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune etiology.
Time Frame
During 90 days (from Day 1 to Day 91)
Secondary Outcome Measure Information:
Title
Number of participants reporting solicited local adverse events (AEs) during the 7-day follow-up period after each vaccination received from Day 1 up to study conclusion at Month 18
Description
The following local AEs are solicited: pain, redness and swelling at injection site.
Time Frame
During the 7-day follow-up period after the third dose (administered at Day 181)
Title
Number of participants reporting solicited general AEs during the 7-day follow-up period after each vaccination received from Day 1 up to study conclusion at Month 18
Description
The following general AEs are solicited: fatigue, fever, nausea, vomiting, diarrhea, abdominal pain and headache.
Fever is defined as temperature ≥ 38.0°C / 100.4°F. The preferred location for measuring temperature in this study is the oral cavity.
Time Frame
During the 7-day follow-up period after the third dose (administered at Day 181)
Title
Number of participants reporting unsolicited AEs during a 30-day follow-up period after each vaccination from Day 1 up to study conclusion at Month 18
Description
Unsolicited AE is defined as an AE reported in addition to those solicited during the clinical study and as any solicited AE with onset outside the specified period of follow-up for solicited symptoms.
Time Frame
During the 30-day follow-up period after the third dose (administered at Day 181)
Title
Number of participants with hematological and biochemical laboratory abnormalities at Day 1, Day 4, Day 8, Day 61, Day 64, Day 68, Day 181, Day 184 and Day 188
Description
Clinically significant abnormal laboratory findings (e.g. clinical chemistry and hematology) are reported. The investigator exercises his or her medical and scientific judgement in deciding whether an abnormal laboratory finding or other abnormal assessment is clinically significant.
Time Frame
At Day 1, Day 4, Day 8, Day 61, Day 64, Day 68, Day 181, Day 184 and Day 188
Title
Number of participants reporting MAEs from Day 1 up to study conclusion at Month 14
Description
A medically attended adverse event is an AE for which the participants received medical attention defined as hospitalization, an emergency room visit or a visit to or from medical personnel (i.e., nurse practitioner or physician assistant or medical doctor) for any reason.
Time Frame
From Day 1 up to study conclusion at Month 14
Title
Number of participants reporting SAEs from Day 1 up to study conclusion at Month 14
Description
SAEs assessed include any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity or is a congenital anomaly/birth defect in the offspring of a study patient.
Time Frame
From Day 1 to up to study end at Month 14
Title
Number of participants reporting pIMDs from Day 1 up to study conclusion at Month 14
Description
pIMDs are a subset of AEs that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune etiology.
Time Frame
From Day 1 up to study conclusion at Month 14
Title
Evaluation of immunogenicity in terms of Rabies Virus Neutralizing Antibody (RVNA) concentrations
Description
RVNA concentrations determined by Rapid Fluorescence Foci Inhibition Test (RFFIT) are presented as geometric mean concentrations (GMCs), expressed in International Unit per milliliter (IU/mL).
Time Frame
At Day 1 and Day 91
Title
Evaluation of immunogenicity in terms of Anti-rabies G IgG antibody concentrations
Description
Anti-rabies G IgG antibody concentrations determined by Enzyme Linked Immunosorbent Assay (ELISA) are presented as GMCs, expressed in ELISA unit per milliliter (EU/mL).
Time Frame
At Day 1 and Day 91
Title
Evaluation of persistence of immunogenicity in terms of anti-rabies G IgG antibody concentrations at 5 months after last vaccination
Description
Anti-rabies G IgG antibody concentrations determined by ELISA are presented as GMCs, expressed in EU/mL.
Time Frame
At Month 7 (i.e. 5 months after the last vaccination)
Title
Evaluation of persistence of immunogenicity in terms of anti-rabies G IgG antibody concentrations at 10 months after last vaccination
Description
Anti-rabies G IgG antibody concentrations determined by ELISA are presented as GMCs, expressed in EU/mL.
Time Frame
At Month 12 (i.e. 10 months after the last vaccination)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Participants who, in the opinion of the investigator, can and will comply with the requirements of the protocol (e.g. participation in genetics research, completion of the electronic diary cards, return for follow-up visits).
Written informed consent obtained from the participant prior to performance of any study specific procedure.
Healthy participants as established by medical history and clinical examination before entering into the study.
A male or female participant between, and including, 18 and 40 years of age at the time of the first vaccination.
Body Mass Index >18 Kg/m^2 and <35 Kg/m^2.
Participants with following hematological/biochemical parameters:
White Blood Cells and differential, within the study designated laboratory normal range. Participants with FDA toxicity grade 1 differential cell counts and considered not clinically significant may be enrolled at the discretion of the investigator, and with the review and approval of the medical monitor.
Platelets = 125,000 - 500,000 cells/mm^3
Hemoglobin within normal range of the study designated laboratory
Alanine aminotransferase within the study designated laboratory normal range
Aspartate aminotransferase within the study designated laboratory normal range
Total bilirubin within the study designated laboratory normal range
Alkaline phosphatase within the study designated laboratory normal range
Serum creatinine less than or equal to 1.1 times study designated laboratory's upper normal limit .
Seronegative for hepatitis B surface antigen, hepatitis C virus antibodies, or human immunodeficiency virus antibodies
Female participants of non-childbearing potential may be enrolled in the study. Non-childbearing potential is defined as pre-menarche, current bilateral tubal ligation or occlusion, hysterectomy, bilateral ovariectomy or post-menopause.
Female participants of childbearing potential may be enrolled in the study, if the participant
has practiced adequate contraception for 30 days prior to vaccination, and
has a negative pregnancy test on the day of vaccination, and
has agreed to continue adequate contraception during the entire treatment period and for 2 months after completion of the vaccination series
Exclusion Criteria:
History of diagnosis with rabies exposure, infection or disease.
Any confirmed or suspected immunosuppressive or immunodeficient condition based on medical history and physical examination.
Family history of congenital or hereditary immunodeficiency.
History of or current autoimmune disease.
History of any reaction or hypersensitivity likely to be exacerbated by any components of RabAvert including polygeline, bovine gelatin, neomycin, chlortetracycline and amphotericin B, chicken protein, egg products or any other vaccine component.
Lymphoproliferative disorder or malignancy within previous 5 years (excluding effectively treated non-melanotic skin cancer).
Hypersensitivity to latex.
History of Type I hypersensitivity reactions to any beta-lactam antibiotics (penicillin, aminopenicillins, cephalosporins and carbapenems).
Any acute or chronic, clinically significant disease, as determined by physical examination, laboratory screening tests, subject personal report and/or General Physician (GP) information.
Use of any investigational or non-registered product other than the study vaccines during the period starting 30 days before the first dose of study vaccines, or planned use during the study period.
Planned administration/administration of a vaccine not foreseen by the study protocol in the period starting 30 days before the vaccination and ending 30 days after (Influenza vaccine excluded).
Previous vaccination with any licensed or investigational rabies vaccine.
Administration of immunoglobulins and/or any blood products within the 3 months preceding the dose of study vaccine or planned administration during the study period.
Chronic administration (defined as more than 14 days in total) of immunosuppressants or other immune-modifying drugs during the period within 6 months prior to the vaccine dose.
Current allergy treatment with allergen immunotherapy with antigen injections, unless on maintenance schedule.
Concomitant or planned administration of antimalarial drugs, to include hydroxychloroquine within 30 days of vaccination.
Current anti-tuberculosis prophylaxis or therapy.
Concurrently participating in another clinical study, at any time during the study period, in which the participant has been/will be exposed to an investigational or a non-investigational vaccine/product.
Pregnant or lactating female participant.
Female participant planning to become pregnant or planning to discontinue contraceptive precautions.
Participants at a higher risk than the average US resident with regard to exposure to rabies, per the RabAvert package insert and rabies vaccination recommendations from the Centers for Disease Control (CDC).
Participants with extensive tattoos covering deltoid region on both the arms that would preclude the assessment of local reactogenicity.
Planned move to a location that will prohibit participating in the trial until study end.
Any medical, psychiatric, social condition, occupational reason or other responsibility that, in the judgment of the investigator, is a contraindication to protocol participation.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
GSK Clinical Trials
Organizational Affiliation
GlaxoSmithKline (for GlaxoSmithKline; Human Genome Sciences Inc., a GSK Company; Sirtris, a GSK Company; Stiefel, a GSK Company; ViiV Healthcare)
Official's Role
Study Director
Facility Information:
Facility Name
GSK Investigational Site
City
South Miami
State/Province
Florida
ZIP/Postal Code
33143
Country
United States
Facility Name
GSK Investigational Site
City
Lenexa
State/Province
Kansas
ZIP/Postal Code
66219
Country
United States
Facility Name
GSK Investigational Site
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Facility Name
GSK Investigational Site
City
Rochester
State/Province
New York
ZIP/Postal Code
14609
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
IPD for this study will be made available via the Clinical Study Data Request site.
IPD Sharing Time Frame
IPD will be made available within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data of the study.
IPD Sharing Access Criteria
Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an exemption can be granted, when justified, for up to another 12 months.
IPD Sharing URL
https://www.clinicalstudydatarequest.com
Learn more about this trial
A Study to Evaluate the Safety and Immunogenicity of GlaxoSmithKline (GSK) Biologicals' Experimental Rabies Vaccine in Healthy Adults
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