Lassa Fever
Conditions
Keywords
Lassa
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.
Detailed description
Lassa fever is a zoonotic infection endemic in West Africa and is spread by the Lassa virus, an arenavirus causing hemorrhagic fever. Up to 300,000 Lassa fever infections occur annually and while disease is often mild, in a subset of individuals disease is characterized by severe anemia, bleeding, encephalopathy, respiratory failure, shock, and high mortality. In some regions of West Africa, up to 15% of hospital admissions are secondary to Lassa fever, and an estimated 5,000 deaths occur annually. During epidemics of disease, case-fatality rates may reach as high as 50% in hospitalized patients. Approximately one-third of infected individuals will develop hearing loss regardless of disease severity, and in a proportion of patients, permanent deafness occurs. Prevention of illness through vaccination is a critical goal in reducing the burden of disease from Lassa fever. There are currently no vaccines or therapeutics demonstrated to be efficacious in the prevention or treatment of Lassa fever. 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.
Interventions
BIOLOGICALLASSARAB+ aPHAD-SEat 700rU
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
BIOLOGICALHDCV Comparator
Sterile, stable, freeze-dried suspension of rabies virus prepared from strain PM-1503-3M
OTHERNormal Saline Placebo
Sterile 0.9% sodium chloride for injection, USP, or normal saline, is a sterile, nonpyrogenic, isotonic solution; each mL contains sodium chloride 9 mg
BIOLOGICALLASSARAB+ aPHAD-SEat 1400rU
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
Sponsors
Wilbur Chen, MD, MS
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Caregiver, Investigator)
Intervention model description
This is a phase 1, randomized, controlled, recipient- and observer-blinded, dose-escalation clinical trial
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
1. Provides written informed consent prior to the initiation of any trial procedures. 2. Able to understand and agrees to comply with all planned trial procedures and be available for all study visits. 3. Age ≥ 18 and ≤50 years at time of enrollment. 4. In good general health and without clinically significant medical, psychiatric, chronic or intermittent health conditions including those listed in
Exclusion criteria
5. 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. 6. 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). 7. 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 8. 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. 9. Has a negative rabies neutralizing antibody test at screening (\< 0.5 IU/mL in RFFIT assay) 10. Screening hematology tests (white blood cells, hemoglobin, and platelets) and screening chemistry tests (alanine transaminase, creatine, and total bilirubin) are within acceptable parameters 11. Must agree to the collection and storage of residual biological specimens and additional clinical specimens for secondary research use 12. Agreement to adhere to Lifestyle Considerations during the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants experiencing solicited local and systemic events | 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 solicited local and systemic reactogenicity Adverse Events (AEs) |
| Percentage of participants experiencing solicited local and systemic events | 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 reactogenicity Adverse Events (AEs) |
| Number of participants experiencing unsolicited events | Day 1 through Day 61 | Number of participants experiencing any unsolicited AEs |
| Percentage of participants experiencing unsolicited events | Day 1 through Day 61 | Percentage of participants experiencing any unsolicited AEs |
| Number of participants experiencing Serious Adverse Events (SAEs) | Day 1 through Day 394 | Number of participants experiencing SAEs |
| Percentage of participants experiencing Serious Adverse Events (SAEs) | Day 1 through Day 394 | Percentage of participants experiencing SAEs |
| Number of participants experiencing Medically-Attended Adverse Events (MAAEs) | Day 1 through Day 394 | Number of participants experiencing MAAEs |
| Percentage of participants experiencing Medically-Attended Adverse Events (MAAEs) | Day 1 through Day 394 | Percentage of participants experiencing MAAEs |
| Number of participants experiencing New-Onset Chronic Medical Conditions (NOCMCs) | Day 1 through Day 394 | Number of participants experiencing NOCMCs |
| Percentage of participants experiencing New-Onset Chronic Medical Conditions (NOCMCs) | Day 1 through Day 394 | Percentage of participants experiencing NOCMCs |
| Number of participants experiencing Potential Immune-Mediated Medical Conditions (PIMMCs) | Day 1 through Day 394 | Number of participants experiencing PIMMCs |
| Percentage of participants experiencing Potential Immune-Mediated Medical Conditions (PIMMCs) | Day 1 through Day 394 | Percentage of participants experiencing PIMMCs |
| Number of participants experiencing Adverse Event of Special Interest (AESI) | Day 1 through Day 394 | Number of participants experiencing Adverse Event of Special Interest (AESI) - new onset sensorineural hearing loss (SNHL) |
| Percentage of participants experiencing Adverse Event of Special Interest (AESI) | Day 1 through Day 394 | Percentage of participants experiencing Adverse Event of Special Interest (AESI) - new onset sensorineural hearing loss (SNHL) |
| Number of participants experiencing clinical laboratory AEs | Day 1 through Day 61 | Number of participants experiencing clinical laboratory AEs |
| Percentage of participants experiencing clinical laboratory AEs | Day 1 through Day 61 | Percentage of participants experiencing clinical laboratory AEs |
Countries
United States
Outcome results
None listed