A Phase 1, Dosage-Escalation Study of the Safety and Immunogenicity of a Novel Rabies Vaccine ChAd155-RG vs. the Comparator RABAVERT Vaccine in Healthy Adult Subjects
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- Rabies
- Sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)
- Enrollment
- 50
- Locations
- 1
- Primary Endpoint
- Number and Percentage of Participants With Solicited Injection Site Reactogenicity Events in Each Treatment Arm and Overall
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
This is a single-center, observer-blinded, dosage-escalation trial to evaluate the safety, tolerability, reactogenicity, and immunogenicity of ChAd155-RG compared with RABAVERT in rabies virus-naïve healthy male and non-pregnant female adult subjects ages 18-49. There are 4 dose groups: Group A will receive ChAd155-RG at the lower dosage (5x1010vp) on Day 1, then placebo injections on Days 8, 15, and 22; Group B will receive ChAd155-RG at the higher dosage (1x1011vp) on Day 1, then placebo injections on Days 8, 15, and 22; Group C will receive ChAd155-RG at the higher dosage (1x1011vp) on Days 1 and 15, and placebo injections on Days 8 and 22; Group D will receive RABAVERT at the standard dose (1 mL) on Days 1, 8, and 22, and a placebo injection on Day 15. Since this is a dosage-escalation study, sentinel subjects will be used at each dosage level before non-sentinel subjects will be enrolled. The study will be conducted at Emory University Vaccine and Treatment Evaluation Unit (VTEU). This trial is expected to take approximately 48 months to complete. The duration of each subject's participation is approximately 13 months, from recruitment through the last study visit. The primary objectives of this study are: 1) Assessment of the safety, tolerability, and reactogenicity of one dose of ChAd155-RG at 5x1010vp per dose, or one or two doses of ChAd155-RG at 1x1011vp per dose; 2) Comparison of the safety, tolerability, and reactogenicity of one or two doses of ChAd155-RG, with three doses of RABAVERT.
Detailed Description
This is a single-center, observer-blinded, Phase 1, dosage-escalation trial to evaluate the safety, tolerability, reactogenicity, and immunogenicity of ChAd155-RG compared with RABAVERT in rabies virus-naïve healthy male and non-pregnant female adult subjects ages 18-49. Subjects who have never received a licensed or investigational rabies virus vaccine, or an Ad-based investigational vaccine, and who have never been exposed to a rabid animal will be eligible for enrollment. There are 4 dose groups: Group A will receive ChAd155-RG at the lower dosage (5x1010vp) on Day 1, then placebo injections on Days 8, 15, and 22; Group B will receive ChAd155-RG at the higher dosage (1x1011vp) on Day 1, then placebo injections on Days 8, 15, and 22; Group C will receive ChAd155-RG at the higher dosage (1x1011vp) on Days 1 and 15, and placebo injections on Days 8 and 22; Group D will receive RABAVERT at the standard dose (1 mL) on Days 1, 8, and 22, and a placebo injection on Day 15. Since this is a dosage-escalation study, sentinel subjects will be used at each dosage level before non-sentinel subjects will be enrolled. The SMC will review the available safety, reactogenicity, AE, and lab data of all the sentinel subjects, and will decide if the remaining non-sentinel subjects should be enrolled. The study will be conducted at Emory University Vaccine and Treatment Evaluation Unit (VTEU). This trial is expected to take approximately 48 months to complete. The duration of each subject's participation is approximately 13 months, from recruitment through the last study visit. The primary objectives of this study are: 1) Assessment of the safety, tolerability, and reactogenicity of one dose of ChAd155-RG at 5x1010vp per dose, or one or two doses of ChAd155-RG at 1x1011vp per dose; 2) Comparison of the safety, tolerability, and reactogenicity of one or two doses of ChAd155-RG, with three doses of RABAVERT. The secondary objective is to assess the serum rabies VNA levels by a standard, WHO-approved, RFFIT, as assessed by immune response kinetics (through approximately 12 months after first dose of vaccine), seroconversion rates, and peak GMT in each treatment arm.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Must be a male or female aged 18-49 years old (inclusive) at the time of first vaccination.
- •Must be able to provide written informed consent.
- •Must have a body mass index (BMI) = / \>18.5 and \<35.0 kg/m\^2
- •Must be in good health based on physical examination, vital signs\*, medical history, safety labs\*\*, and the investigator's clinical judgment.
- •\*Vital signs must be within the normal ranges. If a subject has elevated systolic or diastolic blood pressure, subject may rest for 10 minutes in a quiet room and the blood pressure may be retaken.
- •\*\*Safety lab normal ranges will be those used by the reference clinical lab. Protocol-specific criteria for individual subjects are listed in criteria #
- •Must have acceptable\* lab values within 28 days before enrollment. \*Acceptable values include:
- •Hemoglobin: women \>11.6 g/dL, men \>13.1 g/dL
- •White blood cells: \>3,700 but \<10,900 cells/mm\^3
- •Absolute neutrophil count: = / \>1,500 cells/mm\^3
Exclusion Criteria
- •Was ever vaccinated with a licensed or investigational rabies vaccine\* or was diagnosed with rabies exposure, infection, or disease.
- •\*Includes RABAVERT and Imovax. Subject's verbal history will suffice.
- •Has 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 CDC\*.
- •People at high risk of exposure to rabies, such as veterinarians, animal handlers, rabies laboratory workers, spelunkers, and rabies biologics production workers.
- •People whose activities bring them into frequent contact with rabies virus or with possibly rabid animals.
- •International travelers who are likely to come in contact with animals in parts of the world where rabies is common.
- •Was ever vaccinated with a licensed or investigational Ad vector or Ad vaccine.
- •Is currently taking chloroquine or hydroxychloroquine.
- •Was diagnosed with laboratory-confirmed COVID-19 (PCR or antigen-based test) in the preceding 28 days.
- •Positive serology for HIV antibody, HCV antibody, or Hepatitis B surface antigen (HBsAg).
Outcomes
Primary Outcomes
Number and Percentage of Participants With Solicited Injection Site Reactogenicity Events in Each Treatment Arm and Overall
Time Frame: Day 1 through Day 29
Injection site reactogenicity events were solicited on a memory aid completed by participants from the time of each vaccination through Day 7 following each vaccination. Injection site reactogenicity events included pruritus, erythema, ecchymosis, induration/swelling, pain, and tenderness. Each event was graded as mild, moderate, or severe. Participants are counted according to their maximum severity of injection site event reported. Participants reporting no injection site events are counted under "None".
Number and Percentage of Participants With Serious Adverse Events (SAEs) Considered Study Vaccine-Related in Each Treatment Arm and Overall
Time Frame: Day 1 through Day 381
An AE or suspected AE was considered "serious" if, in the view of either the investigator or sponsor, it resulted in any of the following outcomes: death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital anomaly/birth defect. Events were determined to be related if there was a reasonable possibility that the study product caused the AE; that is, there was evidence to suggest a causal relationship between the study product and the AE. Each event was graded as mild, moderate, or severe. Participants are counted according to their maximum severity of event reported. Participants reporting no vaccine-related SAEs are counted under "None".
Number and Percentage of Participants With Serious Adverse Events (SAEs) in Each Treatment Arm and Overall
Time Frame: Day 1 through Day 381
An AE or suspected AE was considered "serious" if, in the view of either the investigator or sponsor, it resulted in any of the following outcomes: death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital anomaly/birth defect. Each event was graded as mild, moderate, or severe. Participants are counted according to their maximum severity of event reported. Participants reporting no SAEs are counted under "None".
Number and Percentage of Participants With Solicited Systemic Reactogenicity Events in Each Treatment Arm and Overall
Time Frame: Day 1 through Day 29
Systemic reactogenicity events were solicited on a memory aid completed by participants from the time of each vaccination through Day 7 following each vaccination. Systemic reactogenicity events included fever, chills/shivering/sweating, fatigue, malaise, myalgia and arthralgia (exclusive of the injection site), headache, and nausea. Each event was graded as mild, moderate, or severe. Participants are counted according to their maximum severity of systemic event reported. Participants reporting no systemic events are counted under "None".
Number and Percentage of Participants With New Onset of a Chronic Medical Condition in Each Treatment Arm and Overall
Time Frame: Day 1 through Day 381
Participants were queried at each visit for the occurrence of new onset chronic medical conditions throughout the duration of the study.
Number and Percentage of Participants With Study Vaccine-related Lab Adverse Events (AEs) in Each Treatment Arm and Overall
Time Frame: Day 1 through Day 22
Clinical safety lab parameters evaluated after receipt of vaccine (on Days 2, 8, 16, and Day 22) included WBCs, hemoglobin, platelets, absolute neutrophil count, absolute lymphocyte count, ALT, AST, total bilirubin, BUN, and creatinine. Lab events were assessed for relatedness and were determined to be related if there was a reasonable possibility that the study product caused the AE; that is, there was evidence to suggest a causal relationship between the study product and the AE. Each lab event was graded as mild, moderate, or severe. Participants are counted according to their maximum severity of event reported. Participants reporting no lab events are counted under "None".
Number and Percentage of Participants With Unsolicited Study Vaccine-related Adverse Events (AEs) in Each Treatment Arm and Overall
Time Frame: Day 1 through Day 50
Adverse events were defined as any untoward medical occurrence in a patient or clinical investigation participant administered a study product regardless of its causal relationship to the study product administration. Unsolicited, non-serious AEs were collected from participants from Day 1 through Day 28 after the last vaccination (Day 50). Events were determined to be related if there was a reasonable possibility that the study product caused the AE; that is, there was evidence to suggest a causal relationship between the study product and the AE. Each event was graded as mild, moderate, or severe. Participants are counted according to their maximum severity of event reported. Participants reporting no vaccine-related AEs are counted under "None".
Secondary Outcomes
- Percentage of Participants Seroconverting to Rabies Virus in Each Treatment Arm and Overall(Day 8, Day 15, Day 22, Day 29, Day 91, Day 181, and Day 381)
- Peak Rabies VNA Geometric Mean Titer(Day 8 through Day 381)
- Rabies VNA Geometric Mean Titer(Day 1, Day 8, Day 15, Day 22, Day 29, Day 91, Day 181, and Day 381)