West Nile Viral Infection
Conditions
Keywords
Healthy Adults, HydroVax-001B WNV, Immunogenicity, Safety, Vaccine, West Nile Virus
Brief summary
A randomized, placebo controlled, double-blind (within dosing group), sequential dose escalation study. This phase 1 trial addresses the urgent need for a vaccine to prevent disease resulting from infection with West Nile virus (WNV), a virus that is primarily spread to people by the bite of an infected mosquito. The purpose of this Phase 1 trial is to evaluate the safety and immunogenicity of the HydroVax-001B WNV vaccine in healthy adult volunteers. The study Population will consist of healthy male and non-pregnant, non-breastfeeding female adults, 18 to 49 years of age, inclusive. Potential participants with a history of prior flavivirus infection or receipt of any flavivirus vaccine or monoclonal antibody, and those who likely had a prior flavivirus infection based on exposure history will be ineligible for the study. Participants will be randomized to receive HydroVax-001B WNV vaccine or placebo in a 12:3 ratio within a dosage group. Participants will be sequentially enrolled into two dosage groups. The primary objective is to assess the safety and reactogenicity of 4 mcg versus 10 mcg dose of the HydroVax-001B WNV vaccine administered intramuscularly (IM) on Days 1, 29 and 181.
Detailed description
A randomized, placebo controlled, double-blind (within dosing group), sequential dose escalation study. This phase 1 trial addresses the urgent need for a vaccine to prevent disease resulting from infection with West Nile virus (WNV), a virus that is primarily spread to people by the bite of an infected mosquito. The purpose of this Phase 1 trial is to evaluate the safety and immunogenicity of the HydroVax-001B WNV vaccine in healthy adult volunteers. The study Population will consist of healthy male and non-pregnant, non-breastfeeding female adults, 18 to 49 years of age, inclusive. Potential participants with a history of prior flavivirus infection or receipt of any flavivirus vaccine or monoclonal antibody, and those who likely had a prior flavivirus infection based on exposure history will be ineligible for the study. Participants will be randomized to receive HydroVax-001B WNV vaccine or placebo in a 12:3 ratio within a dosage group. Participants will be sequentially enrolled into two dosage groups. The primary objective is to assess the safety and reactogenicity of 4 mcg versus 10 mcg dose of the HydroVax-001B WNV vaccine administered intramuscularly (IM) on Days 1, 29 and 181. The secondary objective is to assess immunogenicity of 4 mcg versus 10 mcg dose of HydroVax-001B WNV vaccine given IM on Days 1, 29 and 181 as measured by WNV-specific focus reduction neutralizing test (FRNT50) after each vaccination.
Interventions
BIOLOGICALHydroVax-001B WNV
A vaccine to West Nile Virus (WNV) that is prepared by propagating naturally attenuated Kunjin strain of WNV on well characterized low-passage Vero cells. The vaccine contains 10 mcg of inactivated purified whole virion WNV formulated in a volume of 0.5 mL/dose with 0.10% aluminum hydroxide, 10% D-sorbitol, 0.001% Polysorbate 80 (Tween80) in 10 mM phosphate-buffer with 350 mM NaCl.
OTHERPlacebo
Placebo
0.9% Sodium Chloride Injection
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
Syringe will be masked
Eligibility
Sex/Gender
ALL
Age
18 Years to 49 Years
Healthy volunteers
Yes
Inclusion criteria
1. Provides written informed consent prior to initiation of any study procedures. 2. Is able to understand and agrees to comply with planned study procedures including being available for all study visits. 3. Agrees to the collection of venous blood per protocol. 4. Is a male or non-pregnant, non-lactating female 18 to 49 years of age, inclusive at time of enrollment. 5. Is in good health.\* \*Good health is defined by the absence of a medical condition described in the
Exclusion criteria
. If the participant has another current, ongoing medical condition, the condition cannot meet any of the following criteria: (1) was first diagnosed within 3 months of enrollment with a clinically significant condition, in the opinion of investigator that has worsened within 3 months of enrollment; (2) had non-elective surgery, clinically significant medical procedure, or hospitalization within 3 months of enrollment; (3) received new prescription for systemic medication within 30 days of enrollment, unless the new prescription is in the same class of agent or a transition from generic to/from brand name equivalent; or (4) takes medication that may pose a risk to participant's safety or impede assessment of adverse events or study endpoints if they participate in the study. 6. Oral temperature is less than 100.4 degrees Fahrenheit at screening. 7. Pulse is 51 to 100 beats per minute, inclusive at screening. 8. Systolic blood pressure is 90 to 140 mmHg, inclusive at screening. 9. Diastolic blood pressure is 55 to 90 mmHg, inclusive at screening. 10. Screening labs must be within acceptable parameters at screening.\* \*Hematology (white blood cell count \[WBC\], hemoglobin and platelet count), serum creatinine, blood urea nitrogen, potassium and liver panel (ALT, AST, and total bilirubin) should fall within the normal range of the clinical reference lab. A low creatinine value, low total bilirubin, or a low ALT value are acceptable for trial inclusion as they are not considered to be clinically significant. If screening lab values are within the normal range of the clinical reference lab but fall within the Grade 1 FDA toxicity table range, these will be considered acceptable for enrollment. Urine glucose must be negative and urine protein \<1+ (trace urine protein is acceptable) at screening to be eligible for the study. Abnormal urine protein in females on their menses can be repeated after menses is finished. 11. Tests for human immunodeficiency virus (HIV) antigens/antibodies, hepatitis B virus (HBV) surface antigen, and hepatitis C virus (HCV) antibodies must be negative at screening. 12. Females who are of childbearing potential\* must agree not to become pregnant during trial. \*Not of childbearing potential includes post-menopausal females (defined as no menses for at least 12 consecutive months without an alternative medical cause for amenorrhea), or surgically sterile females with documented per volunteer report history of hysterectomy, bilateral oophorectomy, tubal ligation/salpingectomy, or Essure(R) placement and at least 3 months have passed since sterilization procedure. 13. Females of childbearing potential must agree to use an acceptable contraception method\* from at least 30 days before the first study vaccination and for the duration of the trial. \*Acceptable forms of contraception include monogamous relationship with a vasectomized male partner who has been vasectomized for 90 days or more prior to enrollment, use of intrauterine devices, birth control pills, hormonal birth control products that are injectable, implantable (subdermal), transdermal or insertable (vaginal ring), barrier methods with spermicide. Females of childbearing potential who practice abstinence (defined as no heterosexual vaginal-penile intercourse) and agree to practice abstinence consistently for the duration of the study or those who have exclusively non-male sexual relations do not need to use contraception. 14. Females of childbearing potential must have a negative serum pregnancy test at screening and a negative urine pregnancy test prior to each study vaccination. 15. Has body mass index (BMI) 18.5 kg/m\^2 to 34.9 kg/m\^2, inclusive.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Frequency of any unsolicited adverse events (AEs) | Day 1 through Day 29 | — |
| Frequency of related Grade 3 laboratory toxicities | Day 1 through Day 15 | — |
| Frequency of related serious adverse events (SAE) overall and in each dose group through the end of the study | Day 1 through study completion, approximately 13 months | Frequency is the number of discontinuous events |
| Frequency of solicited local adverse events (AEs) | Day 1 through Day 8 | — |
| Frequency of solicited systemic adverse events (AEs) | Day 1 through Day 8 | — |
| Incidence of any unsolicited adverse events (AEs) | Day 1 through Day 29 | — |
| Incidence of related Grade 3 laboratory toxicities | Day 1 through Day 15 | — |
| Incidence of related serious adverse events (SAE) overall and in each dose group through the end of the study | Day 1 through study completion, approximately 13 months | Incidence is the number of participants with an event |
| Incidence of solicited local adverse events (AEs) | Day 1 through Day 8 | — |
| Incidence of solicited systemic adverse events (AEs) | Day 1 through Day 8 | — |
| Severity of any unsolicited adverse events (AEs) | Day 1 through Day 29 | — |
| Severity of solicited local adverse events (AEs) | Day 1 through Day 8 | — |
| Severity of solicited systemic adverse events (AEs) | Day 1 through Day 8 | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of participants seroconverting | Day 1 through Day 29 | Seroconversion is defined as greater than or equal to 1:10 in FRNT50 titer. |
| West Nile Virus (WNV)-specific focus reduction neutralizing test (FRNT50) geometric mean titer (GMT) | Day 15 through Day 181 | — |
Countries
United States
Outcome results
None listed