A Study of RBI-4000 in Healthy Participants

NCT06048770 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: RBI-4000-101
• Study Type: interventional
• Target: 89
• Locations: 1 country
• Sites: 2

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).

Conditions

Healthy Volunteers

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (5)

• 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

  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

Study Arms (5)

Multiple Ascending Dose (MAD) Cohorts, Cohort 1: RBI-4000 0.1 mcg

EXPERIMENTAL

Participants will receive RBI-4000 0.1 micrograms (mcg) via intramuscular injection, once on Day 1 and Day 57.

Biological: RBI-4000

MAD Cohorts, Cohort 2: RBI-4000 1 mcg

EXPERIMENTAL

Participants will receive RBI-4000 1 mcg via intramuscular injection, once on Day 1 and Day 57.

Biological: RBI-4000

MAD Cohorts, Cohort 3: RBI-4000 10 mcg

EXPERIMENTAL

Participants will receive RBI-4000 10 mcg via intramuscular injection, single dose on Day 1.

Biological: RBI-4000

MAD Cohorts, Cohort 4: RBI-4000 10 mcg

EXPERIMENTAL

Participants will receive RBI-4000 ,10 mcg via intramuscular injection, once on Day 1 and Day 57.

Biological: RBI-4000

Cohort 5: RabAvert 1 mL

ACTIVE COMPARATOR

Participants will receive RabAvert 1 milliliter (mL), intramuscular injection, once on Day 1 and Day 8.

Biological: RabAvert

Interventions

RBI-4000 BIOLOGICAL

RBI-4000 intramuscular injection.

MAD Cohorts, Cohort 2: RBI-4000 1 mcg; MAD Cohorts, Cohort 3: RBI-4000 10 mcg; MAD Cohorts, Cohort 4: RBI-4000 10 mcg; Multiple Ascending Dose (MAD) Cohorts, Cohort 1: RBI-4000 0.1 mcg

RabAvert BIOLOGICAL

RabAvert intramuscular injection.

Cohort 5: RabAvert 1 mL

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Any gender participants between 18 and 45 years old, inclusive, at the time of the first vaccination.
• Body Mass Index \>18 kilogram per square meter (Kg/m\^2) and less than (\<) 32 Kg/m\^2.
• Hematological/biochemical values within these parameters:
• White Blood Cells and differential, within the study designated laboratory normal range.
• Platelets = 125,000 - 500,000 cells per cubic millimeter (cells/mm\^3)
• Hemoglobin within normal range of the study designated laboratory
• Liver function tests including alanine aminotransferase, aspartate aminotransferase, total bilirubin, and alkaline phosphatase within the study designated laboratory normal range.
• Female participants of non-childbearing potential or male participants with partners of childbearing potential may be enrolled in the study.
• Female participants of childbearing potential may be enrolled in the study, if the participant
• has practiced adequate contraception for 30 days prior to vaccination, and
• has a negative pregnancy test on the day of vaccination (for female participants),
• 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).

You may not qualify if:

• History of diagnosis with rabies exposure, infection or disease.
• History of rabies immunization (licensed or investigational) or human rabies immune globulin.
• Any confirmed or suspected immunosuppressive or immunodeficient condition based on medical history and physical examination.
• Family history of congenital or hereditary immunodeficiency.
• History of or current autoimmune disease.
• History of any reaction or hypersensitivity likely to be exacerbated by any components of commercially available rabies vaccines.
• 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).
• History of Type I hypersensitivity reactions to any beta-lactam antibiotics.
• Any acute or chronic, clinically significant disease, by history, physical examination, laboratory findings, subject personal report, and/or General Physician information.
• Any history of myocarditis and/or pericarditis.
• 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.
• 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.
• Current allergy treatment with allergen immunotherapy with antigen injections, unless on maintenance schedule.
• Concomitant or planned administration of antimalarial drugs, including hydroxychloroquine within 30 days of vaccination.
• Current anti-tuberculosis prophylaxis or therapy.

Sponsors & Collaborators

• Replicate Bioscience: lead

Study Sites (2)

Cordova Research Institute

Miami, Florida, 33155, United States

Location

Velocity Clinical Research

Omaha, Nebraska, 68134, United States

Location

Related Publications (1)

• Maine CJ, Picarda G, Miyake-Stoner SJ, Essink B, Somodevilla G, Sparks J, Geall AJ, Wang NS, Goldberg Z, Aliahmad P. Durability of next-generation self-replicating RNA vaccine RBI-4000: a phase 1, randomized open label clinical trial. Commun Med (Lond). 2025 Sep 24;5(1):392. doi: 10.1038/s43856-025-01147-4.

  PMID: 40993199 DERIVED

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 11, 2023
• First Posted: September 21, 2023
• Study Start: September 1, 2023
• Primary Completion: July 31, 2024
• Study Completion: July 31, 2024
• Last Updated: August 6, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)