DMID 23-0015; Lassa Fever CVD 1000

NCT06546709 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: DMID 23-0015
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 1

Brief Summary

This study proposes the evaluation of a novel, first-in-human Lassa fever vaccine based on the complete Lassa glycoprotein complex (GPC) antigen. The antigen will be presented on a genetically modified and attenuated rabies vector expressing both the rabies glycoprotein (GP) antigen and the Lassa GPC. The inactivated chimeric virus is delivered with a toll-like receptor (TLR-4)-activating oil-in-water emulsion adjuvant. Studies using this vaccine administered as a prime-boost series in mice and non-human primates, and then challenged with Lassa virus demonstrated significant protection against Lassa fever. Given that the vaccine backbone is an attenuated and inactivated rabies virus expressing rabies GP, this vaccine will also be evaluated for immunogenicity against rabies virus.

Conditions

Lassa Fever

Keywords

Lassa

Outcome Measures

Primary Outcomes (16)

• Number of participants experiencing solicited local and systemic events

  Number of participants experiencing solicited local and systemic reactogenicity Adverse Events (AEs)

  From Day 1 through Day 8 for the first vaccination and from Day 29 through Day 36 for the second vaccination, as applicable

• Percentage of participants experiencing solicited local and systemic events

  Percentage of participants experiencing solicited local and systemic reactogenicity Adverse Events (AEs)

  From Day 1 through Day 8 for the first vaccination and from Day 29 through Day 36 for the second vaccination, as applicable

• Number of participants experiencing unsolicited events

  Number of participants experiencing any unsolicited AEs

  Day 1 through Day 61

• Percentage of participants experiencing unsolicited events

  Percentage of participants experiencing any unsolicited AEs

  Day 1 through Day 61

• Number of participants experiencing Serious Adverse Events (SAEs)

  Number of participants experiencing SAEs

  Day 1 through Day 394

• Percentage of participants experiencing Serious Adverse Events (SAEs)

  Percentage of participants experiencing SAEs

  Day 1 through Day 394

• Number of participants experiencing Medically-Attended Adverse Events (MAAEs)

  Number of participants experiencing MAAEs

  Day 1 through Day 394

• Percentage of participants experiencing Medically-Attended Adverse Events (MAAEs)

  Percentage of participants experiencing MAAEs

  Day 1 through Day 394

• Number of participants experiencing New-Onset Chronic Medical Conditions (NOCMCs)

  Number of participants experiencing NOCMCs

  Day 1 through Day 394

• Percentage of participants experiencing New-Onset Chronic Medical Conditions (NOCMCs)

  Percentage of participants experiencing NOCMCs

  Day 1 through Day 394

• Number of participants experiencing Potential Immune-Mediated Medical Conditions (PIMMCs)

  Number of participants experiencing PIMMCs

  Day 1 through Day 394

• Percentage of participants experiencing Potential Immune-Mediated Medical Conditions (PIMMCs)

  Percentage of participants experiencing PIMMCs

  Day 1 through Day 394

• Number of participants experiencing Adverse Event of Special Interest (AESI)

  Number of participants experiencing Adverse Event of Special Interest (AESI) - new onset sensorineural hearing loss (SNHL)

  Day 1 through Day 394

• Percentage of participants experiencing Adverse Event of Special Interest (AESI)

  Percentage of participants experiencing Adverse Event of Special Interest (AESI) - new onset sensorineural hearing loss (SNHL)

  Day 1 through Day 394

• Number of participants experiencing clinical laboratory AEs

  Number of participants experiencing clinical laboratory AEs

  Day 1 through Day 61

• Percentage of participants experiencing clinical laboratory AEs

  Percentage of participants experiencing clinical laboratory AEs

  Day 1 through Day 61

Study Arms (4)

Cohort 1 - LASSARAB+ aPHAD-SE Vaccine at 700rU or Active Comparator (AC)

EXPERIMENTAL

4:1 randomization to investigational vaccine or active comparator (n=5)

Biological: LASSARAB+ aPHAD-SEat 700rU; Biological: HDCV Comparator

Cohort 2 - LASSARAB+ aPHAD-SE Vaccine at 700rU or 1400rU or AC

EXPERIMENTAL

11:4:3 randomization to investigational vaccine dose 700rU or 1400rU or active comparator (n=18)

Biological: LASSARAB+ aPHAD-SEat 700rU; Biological: HDCV Comparator; Biological: LASSARAB+ aPHAD-SEat 1400rU

Cohort 3 - LASSARAB+ aPHAD-SE Vaccine at 1400rU Single or Double or AC or AC/Placebo

EXPERIMENTAL

11:2:4:1 randomization to investigational vaccine single dose at 1400rU or investigational vaccine (2 doses) at 14rU or active comparator or active comparator and normal saline placebo

Biological: HDCV Comparator; Other: Normal Saline Placebo; Biological: LASSARAB+ aPHAD-SEat 1400rU

Cohort 4 - LASSARAB+ aPHAD-SE Vaccine at 1400rU (single) or AC/Placebo

EXPERIMENTAL

11:3 randomization to investigational vaccine (2 doses) at 14rU or active comparator and normal saline placebo

Biological: HDCV Comparator; Other: Normal Saline Placebo; Biological: LASSARAB+ aPHAD-SEat 1400rU

Interventions

LASSARAB+ aPHAD-SEat 700rU BIOLOGICAL

Rabies-Vectored Monovalent Lassa Fever Vaccine (LASSARAB) with 3D-(6- acyl) Phosphorylated Hexaacyl Disaccharides (PHAD)-Stable squalene oil-in-water nanoemulsion (aPHAD-SE) adjuvant administered by IM injection

Cohort 1 - LASSARAB+ aPHAD-SE Vaccine at 700rU or Active Comparator (AC); Cohort 2 - LASSARAB+ aPHAD-SE Vaccine at 700rU or 1400rU or AC

HDCV Comparator BIOLOGICAL

Sterile, stable, freeze-dried suspension of rabies virus prepared from strain PM-1503-3M

Also known as: Imovax

Cohort 1 - LASSARAB+ aPHAD-SE Vaccine at 700rU or Active Comparator (AC); Cohort 2 - LASSARAB+ aPHAD-SE Vaccine at 700rU or 1400rU or AC; Cohort 3 - LASSARAB+ aPHAD-SE Vaccine at 1400rU Single or Double or AC or AC/Placebo; Cohort 4 - LASSARAB+ aPHAD-SE Vaccine at 1400rU (single) or AC/Placebo

Normal Saline Placebo OTHER

Sterile 0.9% sodium chloride for injection, USP, or normal saline, is a sterile, nonpyrogenic, isotonic solution; each mL contains sodium chloride 9 mg

Cohort 3 - LASSARAB+ aPHAD-SE Vaccine at 1400rU Single or Double or AC or AC/Placebo; Cohort 4 - LASSARAB+ aPHAD-SE Vaccine at 1400rU (single) or AC/Placebo

LASSARAB+ aPHAD-SEat 1400rU BIOLOGICAL

Rabies-Vectored Monovalent Lassa Fever Vaccine (LASSARAB) with 3D-(6- acyl) Phosphorylated Hexaacyl Disaccharides (PHAD)-Stable squalene oil-in-water nanoemulsion (aPHAD-SE) adjuvant administered by IM injection

Cohort 2 - LASSARAB+ aPHAD-SE Vaccine at 700rU or 1400rU or AC; Cohort 3 - LASSARAB+ aPHAD-SE Vaccine at 1400rU Single or Double or AC or AC/Placebo; Cohort 4 - LASSARAB+ aPHAD-SE Vaccine at 1400rU (single) or AC/Placebo

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Provides written informed consent prior to the initiation of any trial procedures.
• Able to understand and agrees to comply with all planned trial procedures and be available for all study visits.
• Age ≥ 18 and ≤50 years at time of enrollment.

You may not qualify if:

• Participants of childbearing potential must have a negative serum human chronic gonadotropin (HCG) pregnancy test at screening and a negative urine HCG pregnancy test within 24 hours prior to the study vaccination.
• Participants of childbearing potential in a heterosexual relationship agree to use of highly effective contraception beginning at the time of the screening visit through Day 61 (32 days after the last study treatment).
• Vital signs and Body Mass Index (BMI) are in the following ranges at screening:
• Oral temperature is less than 100.4°F (38.0°C).
• Pulse is 47 to 100 beats per minute, inclusive.
• Systolic blood pressure (SBP) is 85 to 140 mmHg, inclusive.
• Diastolic blood pressure(DBP) is 55 to 90 mmHg, inclusive.
• BMI of 18 kilograms/square meter (kg/m2) (inclusive) to \<35 kg/m2
• Has a negative test result for hepatitis B virus (HBV) surface antigen, hepatitis C virus (HCV) antibody, and human immunodeficiency virus (HIV) types 1 or 2 antibodies at screening.
• Has a negative rabies neutralizing antibody test at screening (\< 0.5 IU/mL in RFFIT assay)
• Screening hematology tests (white blood cells, hemoglobin, and platelets) and screening chemistry tests (alanine transaminase, creatine, and total bilirubin) are within acceptable parameters
• Must agree to the collection and storage of residual biological specimens and additional clinical specimens for secondary research use
• Agreement to adhere to Lifestyle Considerations during the study
• A history of anaphylaxis, serum sickness, meningitis; neuroparalytic events such as encephalitis, transient paralysis; Guillain-Barré Syndrome; myelitis; retrobulbar neuritis; history of prior or current hearing loss as assessed by quantitative audiometry; or multiple sclerosis
• Current use of any medications that may be associated with impaired immune responsiveness

Sponsors & Collaborators

• Wilbur Chen, MD, MS: lead

Study Sites (1)

University of Maryland, Baltimore, University of Maryland School of Medicine, Center for Vaccine Development and Global Health

Baltimore, Maryland, 21201, United States

Location

MeSH Terms

Conditions

Lassa Fever

Interventions

Rabies Vaccines

Condition Hierarchy (Ancestors)

Arenaviridae Infections; RNA Virus Infections; Virus Diseases; Infections; Hemorrhagic Fevers, Viral

Intervention Hierarchy (Ancestors)

Viral Vaccines; Vaccines; Biological Products; Complex Mixtures

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Frank M. Calia, MD Endowed Professor and Interim Chief, Division of Geographic Medicine, Department of Medicine (Sponsor Representative)

Model Details: This is a phase 1, randomized, controlled, recipient- and observer-blinded, dose-escalation clinical trial

Study Record Dates

• First Submitted: July 30, 2024
• First Posted: August 9, 2024
• Study Start: January 13, 2025
• Primary Completion: May 1, 2026
• Study Completion: May 1, 2026
• Last Updated: June 1, 2026

Record last verified: 2026-05

Locations

US (1)