Dosage-Escalation Study of the Safety and Immunogenicity of a Novel Rabies Vaccine ChAd155-RG vs. the Comparator RABAVERT Vaccine in Healthy Adult Subjects

NCT04019444 | Completed Phase 1 Results FDA Drug

• 1 other identifier: 17-0089
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

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.

Conditions

Rabies; Rabies Immunisation

Keywords

Adults; ChAd155-RG; Dosage-Escalation; Healthy; Immunogenicity; RABAVERT; Rabies; Safety; Vaccine

Outcome Measures

Primary Outcomes (7)

• Number and Percentage of Participants With Solicited Injection Site Reactogenicity Events in Each Treatment Arm and Overall

  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".

  Day 1 through Day 29

• Number and Percentage of Participants With Solicited Systemic Reactogenicity Events in Each Treatment Arm and Overall

  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".

  Day 1 through Day 29

• Number and Percentage of Participants With Serious Adverse Events (SAEs) Considered Study Vaccine-Related in Each Treatment Arm and Overall

  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".

  Day 1 through Day 381

• Number and Percentage of Participants With Study Vaccine-related Lab Adverse Events (AEs) in Each Treatment Arm and Overall

  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".

  Day 1 through Day 22

• Number and Percentage of Participants With Unsolicited Study Vaccine-related Adverse Events (AEs) in Each Treatment Arm and Overall

  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".

  Day 1 through Day 50

• Number and Percentage of Participants With New Onset of a Chronic Medical Condition in Each Treatment Arm and Overall

  Participants were queried at each visit for the occurrence of new onset chronic medical conditions throughout the duration of the study.

  Day 1 through Day 381

• Number and Percentage of Participants With Serious Adverse Events (SAEs) in Each Treatment Arm and Overall

  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".

  Day 1 through Day 381

Secondary Outcomes (3)

• 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

• Rabies VNA Geometric Mean Titer

  Day 1, 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

Study Arms (4)

Arm A

EXPERIMENTAL

One dose (1 ml (5x10\^10 vp)) of ChAd155-RG vaccine administered intramuscularly on Day 1, and 1 ml of matching placebo administered intramuscularly on Days 8, 15, 22. N=14 (3 sentinel, 11 non-sentinel)

Biological: ChAd155-RG; Other: Placebo

Arm B

EXPERIMENTAL

One dose (1 ml (1x10\^11 vp)) of ChAd155-RG vaccine administered intramuscularly on Day 1, and 1 ml of matching placebo administered intramuscularly on Days 8, 15, 22. N=14 (3 sentinel, 11 non-sentinel)

Biological: ChAd155-RG; Other: Placebo

Arm C

EXPERIMENTAL

Two doses (1 ml (1x10\^11 vp) each) of ChAd155-RG vaccine administered intramuscularly on Day 1 (first dose) and Day 15 (second dose), and 1 ml of matching placebo administered intramuscularly on Days 8 and 22. N=10

Biological: ChAd155-RG; Other: Placebo

Arm D

ACTIVE COMPARATOR

Three doses (1 ml each) of RABAVERT vaccine administered intramuscularly on Day 1 (first dose), Day 8 (second dose), and Day 22 (third dose), and 1 ml of matching placebo administered intramuscularly on Day 15. N=12 (2 sentinel, 10 non-sentinel)

Other: Placebo; Biological: Rabies Vaccine

Interventions

ChAd155-RG BIOLOGICAL

The ChAd155-RG Vaccine consists of a replication-defective group C ChAd, ChAd155, expressing RG under the control of the CMV promoter. The RG sequence cloned into the ChAd155 vector is a medoid, a natural viral strain with the highest average percent of amino acid identity among all RG sequences annotated in the NCBI database. The selected RG (NCBI strain AGN94271) shares an average 94% percent identity to the RGs in current vaccines.

Arm A; Arm B; Arm C

Placebo OTHER

0.9% Sodium Chloride, USP injection.

Arm A; Arm B; Arm C; Arm D

Rabies Vaccine BIOLOGICAL

The RABAVERT Vaccine is an inactivated, purified chick embryo cell vaccine (PCECV). It consists of lyophilized rabies virus (strain Flury LEP) that has been propagated in chicken fibroblasts, inactivated with beta-propiolactone, and concentrated and purified by centrifugation

Arm D

Eligibility Criteria

• Age: 18 Years - 49 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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 #5.
• 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
• Absolute lymphocyte count: = / \>850 cells/mm\^3
• Platelets: \>139,000 but \<401,000 per mm\^3
• Urine dipstick (clean urine sample): protein \<1+, glucose negative
• Alanine transaminase and aspartate transaminase (ALT, AST) \<1.1 x institutional upper limit of normal (ULN)
• Total bilirubin \<1.1x institutional ULN

You may not qualify if:

• 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).
• Has known allergy or history of anaphylaxis or other serious adverse reaction to a vaccine or vaccine products\*.
• \*Including egg products, aminoglycosides, gelatin, sorbitol, tris (hydroxymethyl)-amino methane (THAM), or any of the constituents of the study vaccines.
• Has severe allergy or anaphylaxis to latex.
• Has an acute illness or temperature = / \>38.0 Degrees Celsius on Day 1\*.
• \*Subjects with fever or acute illness on the day of vaccination may be re-assessed and enrolled if healthy or only minor residual symptoms remain within 3 days.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

The Hope Clinic of Emory University

Decatur, Georgia, 30030-1705, United States

Location

Related Publications (1)

• Phadke VK, Gromer DJ, Rebolledo PA, Graciaa DS, Wiley Z, Sherman AC, Scherer EM, Leary M, Girmay T, McCullough MP, Min JY, Capone S, Sommella A, Vitelli A, Retallick J, Seetahal J, Koller M, Tsong R, Neill-Gubitz H, Mulligan MJ, Rouphael NG. Safety and immunogenicity of a ChAd155-vectored rabies vaccine compared with inactivated, purified chick embryo cell rabies vaccine in healthy adults. Vaccine. 2024 Dec 2;42(26):126441. doi: 10.1016/j.vaccine.2024.126441. Epub 2024 Oct 16.

  PMID: 39418686 DERIVED

MeSH Terms

Conditions

Rabies

Interventions

Rabies Vaccines

Condition Hierarchy (Ancestors)

Rhabdoviridae Infections; Mononegavirales Infections; RNA Virus Infections; Virus Diseases; Infections

Intervention Hierarchy (Ancestors)

Viral Vaccines; Vaccines; Biological Products; Complex Mixtures

Results Point of Contact

• Title: Varun K. Phadke, MD
• Organization: The Hope Clinic of the Emory Vaccine Center

vphadke@emory.edu

404-712-9046

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: SEQUENTIAL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 11, 2019
• First Posted: July 15, 2019
• Study Start: September 19, 2019
• Primary Completion: March 24, 2023
• Study Completion: March 24, 2023
• Last Updated: June 3, 2024
• Results First Posted: April 10, 2024

Record last verified: 2019-07-05

Locations

US (1)