A Study of RBI-4000 in Healthy Participants

A Study to Evaluate the Safety, Reactogenicity and Immunogenicity of RBI-4000 in Healthy Volunteers

The primary purpose of the study is to evaluate the safety, reactogenicity, and immunogenicity of RBI-4000 administered at various dose levels via intramuscular injection and to determine the lowest dose of RBI-4000 necessary to elicit the rabies virus neutralizing antibody titer of equal or greater than (>=) 0.5 international unit per milliliter (IU/mL).

Study Overview

• Status: Active, not recruiting
• Conditions: Healthy Volunteers
• Intervention / Treatment: Biological: RBI-4000; Biological: RabAvert

• Study Type: Interventional
• Enrollment (Estimated): 84
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33155
      • Cordova Research Institute
  • Nebraska
    • Omaha, Nebraska, United States, 68134
      • Velocity Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Any gender participants between 18 and 45 years old, inclusive, at the time of the first vaccination.
2. Body Mass Index >18 kilogram per square meter (Kg/m^2) and less than (<) 32 Kg/m^2.

3. Hematological/biochemical values within these parameters:

   1. White Blood Cells and differential, within the study designated laboratory normal range.
   2. Platelets = 125,000 - 500,000 cells per cubic millimeter (cells/mm^3)
   3. Hemoglobin within normal range of the study designated laboratory
   4. Liver function tests including alanine aminotransferase, aspartate aminotransferase, total bilirubin, and alkaline phosphatase within the study designated laboratory normal range.
4. Female participants of non-childbearing potential or male participants with partners of childbearing potential may be enrolled in the study.

5. Female participants of childbearing potential may be enrolled in the study, if the participant

   1. has practiced adequate contraception for 30 days prior to vaccination, and
   2. has a negative pregnancy test on the day of vaccination (for female participants),
   3. has agreed to continue adequate contraception during the entire treatment period and for 2 months after completion of the vaccination series and agrees to not donate sperm (for male participants).

Exclusion Criteria:

1. History of diagnosis with rabies exposure, infection or disease.
2. History of rabies immunization (licensed or investigational) or human rabies immune globulin.
3. Any confirmed or suspected immunosuppressive or immunodeficient condition based on medical history and physical examination.
4. Family history of congenital or hereditary immunodeficiency.
5. History of or current autoimmune disease.
6. History of any reaction or hypersensitivity likely to be exacerbated by any components of commercially available rabies vaccines.
7. Lymphoproliferative disorder or malignancy within previous 5 years (excluding effectively treated non-melanotic skin cancer, Ductal carcinoma in situ /Lobular carcinoma in situ (DCIS/LCIS).
8. History of Type I hypersensitivity reactions to any beta-lactam antibiotics.
9. Any acute or chronic, clinically significant disease, by history, physical examination, laboratory findings, subject personal report, and/or General Physician information.
10. Any history of myocarditis and/or pericarditis.
11. 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.
12. Chronic administration (defined as more than 14 days in total) of immunosuppressants or other immune-modifying drugs including steroids during the period within 6 months prior to the vaccine dose.
13. Current allergy treatment with allergen immunotherapy with antigen injections, unless on maintenance schedule.
14. Concomitant or planned administration of antimalarial drugs, including hydroxychloroquine within 30 days of vaccination.
15. Current anti-tuberculosis prophylaxis or therapy.
16. Pregnant or lactating female participant.
17. Female participant planning to become pregnant or planning to discontinue contraceptive precautions.
18. Participants with extensive tattoos covering deltoid region on both the arms that would preclude the assessment of local reactogenicity.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Single

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Multiple Ascending Dose (MAD) Cohorts, Cohort 1: RBI-4000 0.1 mcg; Participants will receive RBI-4000 0.1 micrograms (mcg) via intramuscular injection, once on Day 1 and Day 57.	Biological: RBI-4000; RBI-4000 intramuscular injection.
Experimental: MAD Cohorts, Cohort 2: RBI-4000 1 mcg; Participants will receive RBI-4000 1 mcg via intramuscular injection, once on Day 1 and Day 57.	Biological: RBI-4000; RBI-4000 intramuscular injection.
Experimental: MAD Cohorts, Cohort 3: RBI-4000 10 mcg; Participants will receive RBI-4000 10 mcg via intramuscular injection, single dose on Day 1.	Biological: RBI-4000; RBI-4000 intramuscular injection.
Experimental: MAD Cohorts, Cohort 4: RBI-4000 10 mcg; Participants will receive RBI-4000 ,10 mcg via intramuscular injection, once on Day 1 and Day 57.	Biological: RBI-4000; RBI-4000 intramuscular injection.
Active Comparator: Cohort 5: RabAvert 1 mL; Participants will receive RabAvert 1 milliliter (mL), intramuscular injection, once on Day 1 and Day 8.	Biological: RabAvert; RabAvert intramuscular injection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency of any Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)	TEAEs and SAEs measured per the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials (FDA 2007).	Day 1 up to 18 months
Immunogenicity of RBI-4000 Measured by Neutralizing Antibody Titers	Measured by neutralizing antibody titers >=0.5 IU/mL.	Day 1 up to 18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Titer level of Rabies Virus Neutralizing Antibody		Day 1 and up to 18 months
Durability of RBI-4000 Against Rabies Assessed by T-cell Levels	Durability of RBI-4000 against rabies assessed by quantifying cytokine-producing T cells by ELISpot and flow cytometry.	Day 1 and up to 18 months
Rate of RBI-4000 Decay Over Time		Day 1 and up to 18 months
Length of Time Above the Recognized Antibody Correlate of Protection Value		Day 1 and up to 18 months
Lowest Dose of RBI-4000 that Provides Durable (greater than [>] 6 months) Coverage Above the Correlate of Protection		Day 1 and up to 18 months

Collaborators and Investigators

• Sponsor: Replicate Bioscience

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2023
• Primary Completion (Estimated): April 14, 2025
• Study Completion (Estimated): April 14, 2025

Study Registration Dates

• First Submitted: September 11, 2023
• First Submitted That Met QC Criteria: September 20, 2023
• First Posted (Actual): September 21, 2023

Study Record Updates

• Last Update Posted (Actual): March 8, 2024
• Last Update Submitted That Met QC Criteria: March 6, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Other Study ID Numbers: RBI-4000-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No