Rabies
Conditions
Brief summary
The purpose of this study is to compare the effectiveness of a two dose versus a three dose schedule and intramuscular versus intradermal injection for pre-exposure prophylaxis.
Detailed description
This is an exploratory vaccine trial to evaluate immunogenicity of a non-licensed dosing schedule and route of administration for a currently FDA licensed rabies vaccine for pre-exposure prophylaxis against rabies infection. The goal of this study is to characterize the immune response and persistence of immunity to a shortened dose schedule and intradermal (ID) administration, relative to the current licensed dosing schedule of the rabies vaccine (3 dose (0, 7, 21 days) IM). Rabies virus is endemic throughout the world due to high rates of both wild and domestic animal rabies and the risk to deployed military in endemic areas is considerable. Currently the commonly supported pre-exposure prophylaxis regimen for rabies, in the United States is comprised of three, 1.0 ml intramuscular (IM) injections of the human diploid cell vaccine (HDCV) or purified chick embryo cell (PCEC) rabies vaccine on days 0, 7, and 21 or 28. Modified, two and three dose schedules of intradermal (ID) injections of 0.1 ml of HDCV and PCEC are utilized outside the US. These two and three dose intradermal schedules share a similar safety and immunogenicity profile to intramuscular vaccinations and are easily boosted at one year after vaccination. A death, from rabies, of a US Soldier returned from Afghanistan underscores the importance of rabies pre-exposure prophylaxis for soldiers and the need to evaluate the safest, most effective means of vaccinating large deploying forces. While the current three dose, 1 ml IM rabies series is effective, a shortened, equally effective vaccination series with significantly smaller dose per injection would greatly improve the logistics and cost associated with universal or even targeted coverage of deploying soldiers. Evaluation of a shorter, smaller-dose, pre-exposure vaccination series for rabies is the goal of this study.
Interventions
DRUGRabies vaccine
Compare dose schedule and route of administration
DRUGPlacebo
Placebo
Sponsors
Walter Reed Army Institute of Research (WRAIR)
State University of New York - Upstate Medical University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
Male and non-pregnant females aged ≥ 18 to ≤ 60 years on the day of inclusion Able to comprehend and give informed consent Able to attend all scheduled visits and to comply with all trial procedures Subject in good health, based on medical history and physical examination
Exclusion criteria
1. Subject is pregnant, or lactating, or of childbearing potential (to be considered of non-childbearing potential, a female must be post- menopausal for at least 1 year, surgically sterile, or using an effective method of contraception or abstinence from at least 4 weeks prior to the first vaccination and until at least 4 weeks after the last vaccination). 2. Participation in the 4 weeks preceding the first trial vaccination, or planned participation during the present trial period, in another clinical trial investigating a vaccine, drug, medical device, or medical procedure. 3. Previous history of receiving the rabies vaccine. 4. Previous history of receiving rabies immune globulin. 5. Any major psychiatric disorder, such as severe depression, severe anxiety disorder, psychosis, schizophrenia, other major psychiatric disorders, or seizures. History of mild depression or anxiety disorder that is well controlled is not an
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Protective Humoral Immune Response at 1 Month Post First Vaccination. | 1 month post first vaccination | Percentage of subjects achieving the protective titer of ≥ 0.5 IU/ml against rabies virus |
| Protective Humoral Immune Response 12 Months Post First Vaccination. | 12 months post first vaccination | Percentage of subjects achieving the protective titer of ≥ 0.5 IU/ml against rabies virus 12 months post vaccinations (prior to boost). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Protective Humoral Immune Response 7 Days Post Booster at 12 Months Post First Vaccination. | up to 13 months post first vaccination | Percentage of subjects achieving the protective titer of ≥ 0.5 IU/ml against rabies virus at 7 days post boost. |
Countries
United States
Participant flow
Pre-assignment details
One subject in group 4 was lost to follow up prior to receiving vaccine.
Participants by arm
| Arm | Count |
|---|---|
| Rabies Vaccine IM 3 Dose This is standard FDA approved schedule
Rabies vaccine: Compare dose schedule and route of administration | 12 |
| Rabies Vaccine ID 3 Dose This is using alternative administration method
Rabies vaccine: Compare dose schedule and route of administration | 12 |
| Rabies Vaccine IM 2 Dose This is using alternative dose schedule
Rabies vaccine: Compare dose schedule and route of administration | 12 |
| Rabies Vaccine ID 2 Dose This is using alternative dose schedule and administration
Rabies vaccine: Compare dose schedule and route of administration | 11 |
| Placebo IM 1 Dose Albumin and saline comparator
Placebo: Placebo | 6 |
| Placebo ID 1 Dose Albumin and saline comparator
Placebo: Placebo | 6 |
| Total | 59 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 1 | 0 | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 1 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Rabies Vaccine ID 3 Dose | Rabies Vaccine IM 2 Dose | Rabies Vaccine ID 2 Dose | Placebo IM 1 Dose | Placebo ID 1 Dose | Rabies Vaccine IM 3 Dose | Total |
|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants | 12 Participants | 10 Participants | 6 Participants | 6 Participants | 12 Participants | 58 Participants |
| Age, Continuous | 29.3 Years STANDARD_DEVIATION 9.5 | 32.3 Years STANDARD_DEVIATION 10 | 31.8 Years STANDARD_DEVIATION 12.6 | 38.5 Years STANDARD_DEVIATION 15.3 | 35.7 Years STANDARD_DEVIATION 10.6 | 31.7 Years STANDARD_DEVIATION 7 | 32.4 Years STANDARD_DEVIATION 10.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 12 Participants | 12 Participants | 11 Participants | 6 Participants | 4 Participants | 12 Participants | 57 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 9 Participants | 10 Participants | 11 Participants | 6 Participants | 6 Participants | 12 Participants | 54 Participants |
| Region of Enrollment United States | 12 participants | 12 participants | 11 participants | 6 participants | 6 participants | 12 participants | 59 participants |
| Sex: Female, Male Female | 8 Participants | 8 Participants | 8 Participants | 4 Participants | 3 Participants | 7 Participants | 38 Participants |
| Sex: Female, Male Male | 4 Participants | 4 Participants | 3 Participants | 2 Participants | 3 Participants | 5 Participants | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 12 | 0 / 12 | 0 / 11 | 0 / 6 | 0 / 6 |
| other Total, other adverse events | 10 / 12 | 12 / 12 | 8 / 12 | 11 / 11 | 1 / 6 | 0 / 6 |
| serious Total, serious adverse events | 0 / 12 | 0 / 12 | 0 / 12 | 0 / 11 | 0 / 6 | 0 / 6 |
Outcome results
Primary
Protective Humoral Immune Response 12 Months Post First Vaccination.
Percentage of subjects achieving the protective titer of ≥ 0.5 IU/ml against rabies virus 12 months post vaccinations (prior to boost).
Time frame: 12 months post first vaccination
Population: One subject in each of groups 1, 2, and 4 were lost to follow up prior to vaccination boost. Placebo groups were used for adverse event data collection only. It was not expected that placebo group would elicit any antibody titer to rabies. Samples in groups 5 and 6 were not analyzed for primary or secondary outcome measures.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Rabies Vaccine IM 3 Dose | Protective Humoral Immune Response 12 Months Post First Vaccination. | 7 Participants |
| Rabies Vaccine ID 3 Dose | Protective Humoral Immune Response 12 Months Post First Vaccination. | 5 Participants |
| Rabies Vaccine IM 2 Dose | Protective Humoral Immune Response 12 Months Post First Vaccination. | 7 Participants |
| Rabies Vaccine ID 2 Dose | Protective Humoral Immune Response 12 Months Post First Vaccination. | 6 Participants |
Primary
Protective Humoral Immune Response at 1 Month Post First Vaccination.
Percentage of subjects achieving the protective titer of ≥ 0.5 IU/ml against rabies virus
Time frame: 1 month post first vaccination
Population: Placebo groups were used for adverse event data collection only. It was not expected that placebo group would elicit any antibody titer to rabies. Samples in groups 5 and 6 were not analyzed for primary or secondary outcome measures.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Rabies Vaccine IM 3 Dose | Protective Humoral Immune Response at 1 Month Post First Vaccination. | 12 Participants |
| Rabies Vaccine ID 3 Dose | Protective Humoral Immune Response at 1 Month Post First Vaccination. | 12 Participants |
| Rabies Vaccine IM 2 Dose | Protective Humoral Immune Response at 1 Month Post First Vaccination. | 12 Participants |
| Rabies Vaccine ID 2 Dose | Protective Humoral Immune Response at 1 Month Post First Vaccination. | 11 Participants |
Secondary
Protective Humoral Immune Response 7 Days Post Booster at 12 Months Post First Vaccination.
Percentage of subjects achieving the protective titer of ≥ 0.5 IU/ml against rabies virus at 7 days post boost.
Time frame: up to 13 months post first vaccination
Population: One subject in group 3 and one in 4 withdrew consent not due to adverse events. Placebo groups were used for adverse event data collection only. It was not expected that placebo group would elicit any antibody titer to rabies. Samples in groups 5 and 6 were not analyzed for primary or secondary outcome measures.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Rabies Vaccine IM 3 Dose | Protective Humoral Immune Response 7 Days Post Booster at 12 Months Post First Vaccination. | 11 Participants |
| Rabies Vaccine ID 3 Dose | Protective Humoral Immune Response 7 Days Post Booster at 12 Months Post First Vaccination. | 11 Participants |
| Rabies Vaccine IM 2 Dose | Protective Humoral Immune Response 7 Days Post Booster at 12 Months Post First Vaccination. | 11 Participants |
| Rabies Vaccine ID 2 Dose | Protective Humoral Immune Response 7 Days Post Booster at 12 Months Post First Vaccination. | 9 Participants |