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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
QUADRUPLE
Enrollment
160
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.
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.
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)
GSK Investigational Site
South Miami, Florida, United States
GSK Investigational Site
Lenexa, Kansas, United States
GSK Investigational Site
Baltimore, Maryland, United States
GSK Investigational Site
Rochester, New York, United States
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.
Time frame: During the 7-day follow-up period after the first dose (administered at Day 1)
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.
Time frame: During the 7-day follow-up period after the second dose (administered at Day 61)
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.
Time frame: During the 7-day follow-up period after the first dose (administered at Day 1)
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.
Time frame: During the 7-day follow-up period after the second dose (administered at Day 61)
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.
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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)
Subjects in the Saline Placebo group will receive 2 doses of saline Placebo, administered intramuscularly Day 1 and 61.
Subjects in the RabAvert Group will receive 2 doses of RabAvert vaccine, administered intramuscularly, at Days 1 and 61.
Time frame: During the 30-day follow-up period after the first dose (administered at Day 1).
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.
Time frame: During the 30-day follow-up period after the second dose (administered at Day 61).
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.
Time frame: At Day 1
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.
Time frame: At Day 4.
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.
Time frame: At Day 8.
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.
Time frame: At Day 61.
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.
Time frame: At Day 64.
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.
Time frame: At Day 68.
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.
Time frame: During 90 days (from Day 1 to Day 91)
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.
Time frame: During 90 days (from Day 1 to Day 91)
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.
Time frame: During 90 days (from Day 1 to Day 91)
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.
Time frame: During the 7-day follow-up period after the third dose (administered at Day 181)
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.
Time frame: During the 7-day follow-up period after the third dose (administered at Day 181)
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.
Time frame: During the 30-day follow-up period after the third dose (administered at Day 181)
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.
Time frame: At Day 1, Day 4, Day 8, Day 61, Day 64, Day 68, Day 181, Day 184 and Day 188
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.
Time frame: From Day 1 up to study conclusion at Month 14
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.
Time frame: From Day 1 to up to study end at Month 14
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.
Time frame: From Day 1 up to study conclusion at Month 14
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).
Time frame: At Day 1 and Day 91
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).
Time frame: At Day 1 and Day 91
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.
Time frame: At Month 7 (i.e. 5 months after the last vaccination)
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.
Time frame: At Month 12 (i.e. 10 months after the last vaccination)