A Study of RBI-4000 in Healthy Participants

• ClinicalTrials.gov Identifier: NCT06048770
• Recruitment Status: Active, not recruiting
• First Posted: September 21, 2023
• Last Update Posted: March 8, 2024
• Sponsor: Replicate Bioscience
• Information provided by (Responsible Party): Replicate Bioscience

Study Description

Brief Summary:

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).

Condition or disease	Intervention/treatment	Phase
Healthy Volunteers	Biological: RBI-4000; Biological: RabAvert	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 84 participants
• Allocation: Randomized
• Intervention Model: Sequential Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Other
• Official Title: A Study to Evaluate the Safety, Reactogenicity and Immunogenicity of RBI-4000 in Healthy Volunteers
• Actual Study Start Date: September 1, 2023
• Estimated Primary Completion Date: April 14, 2025
• Estimated Study Completion Date: April 14, 2025

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

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

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 45 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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.

Contacts and Locations

Locations

United States, Florida

Cordova Research Institute

Miami, Florida, United States, 33155

United States, Nebraska

Velocity Clinical Research

Omaha, Nebraska, United States, 68134

Sponsors and Collaborators

Replicate Bioscience

More Information

• Responsible Party: Replicate Bioscience
• ClinicalTrials.gov Identifier: NCT06048770
• Other Study ID Numbers: RBI-4000-101
• First Posted: September 21, 2023
• Last Update Posted: March 8, 2024
• Last Verified: March 2024

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No