Trial for Safety and Immunogenicity of a Chikungunya Vaccine, VRC-CHKVLP059-00-VP, in Healthy Adults

Phase 2 Randomized, Placebo-Controlled Trial to Evaluate the Safety and Immunogenicity of a Chikungunya Virus-Like Particle Vaccine, VRC-CHKVLP059-00-VP, in Healthy Adults

This is a multicenter, randomized, placebo-controlled, double-blind study to evaluate the safety and immunogenicity of a 2-injection vaccine Chikungunya virus (CHIKV) virus-like particle vaccine (CHIKV VLP) in healthy adults.

This is a Phase 2, multicenter, randomized, placebo-controlled, double-blind study to evaluate the safety and immunogenicity of a 2-injection vaccine regimen (Day 0 and 28) with Chikungunya virus (CHIKV) virus-like particle vaccine (CHIKV VLP, VRC-CHKVLP059-00-VP) in healthy adults ages 18-60 years old that reside in CHIKV endemic regions.

The hypothesis is that the vaccine regimen is safe and induces a neutralizing antibody response to CHIKV. The primary objectives are to evaluate safety and tolerability of a 2-injection investigational vaccine regimen of VRC-CHKVLP059-00-VP at 20 mcg compared to placebo (PBS) in healthy adults in CHIKV endemic areas. The secondary objective is to evaluate neutralizing antibody response in vaccine recipients. The exploratory objectives relate to assessing incidence of CHIKV infection in vaccine and placebo recipients, as well as antigen-specific humoral and cellular immune responses during the study.

The expected study duration per subject is approximately 72 weeks with intramuscular (IM) injections scheduled at Day 0 and Day 28.

Inclusion Criteria:

A subject must meet all of the following criteria:

• 18 to 60 years old
• Available for clinical follow-up through Study Week 72
• Able to provide proof of identity to the satisfaction of the study clinician completing the enrollment process
• Able and willing to complete the informed consent process
• Willing to donate blood for sample storage to be used for future research
• In good general health, with a body mass index (BMI)≤40, without clinically significant medical history, and has satisfactorily completed screening
• Physical examination and laboratory results without clinically significant findings within the 56 days prior to enrollment

Laboratory Criteria within 56 days prior to enrollment:

• Hemoglobin either within institutional normal limits or accompanied by site physician approval as consistent with healthy adult status
• White blood cells either within institutional normal range or accompanied by site physician approval as consistent with healthy adult status
• Platelets = 125,000 - 500,000/mm3
• Alanine aminotransferase (ALT) ≤ 1.25 x upper limit of normal (ULN)
• Serum creatinine ≤ 1.1 x ULN based on site institutional normal range
• Negative result on a human immunodeficiency virus (HIV) test that meets local standards for identification of HIV infection
• Negative result on the Chikungunya virus (CHIKV) screening antibody assay.

Criteria applicable to women of childbearing potential:

• Negative human chorionic gonadotropin pregnancy test (urine or serum) on day of enrollment
• Agree to use an effective means of birth control from 21 days prior to enrollment through 12 weeks after the last study injection

Exclusion Criteria:

A subject will be excluded if one or more of the following conditions apply:

Women Specific:

-Planning to become pregnant during the 16 weeks after enrollment in the study

Subject has received any of the following substances:

• Systemic immunosuppressive medications within 2 weeks prior to enrollment
• Blood products within 16 weeks prior to enrollment
• Immunoglobulin within 8 weeks prior to enrollment
• Prior vaccinations with an investigational CHIKV vaccine
• Investigational research agents within 4 weeks prior to enrollment
• Any vaccination within 2 weeks prior to enrollment
• Current anti-tuberculosis (TB) prophylaxis or therapy

Subject has a history of any of the following clinically significant conditions:

• A history of immune-mediated or clinically significant arthritis
• Serious reactions to vaccines that preclude receipt of study injections as determined by the investigator
• Hereditary angioedema, acquired angioedema, or idiopathic forms of angioedema
• Asthma that is unstable or required emergent care, urgent care, hospitalization or intubation during the past two years or that is expected to require the use of oral or intravenous corticosteroids
• Diabetes mellitus (type I or II), with the exception of gestational diabetes
• Idiopathic urticaria within the past year
• Bleeding disorder diagnosed by a doctor (e.g. factor deficiency, coagulopathy, or platelet disorder requiring special precautions) or significant bruising or bleeding difficulties with intramuscular (IM) injections or blood draws
• Malignancy that is active or history of a malignancy that is likely to recur during the period of the study
• Seizure in the past 3 years or treatment for a seizure disorder within the last 3 years
• Asplenia, functional asplenia or any condition resulting in the absence or removal of the spleen
• Psychiatric condition that may preclude compliance with the protocol; past or present psychoses; or a history of suicide plan or attempt within the five years prior to enrollment
• Any medical or social condition that, in the judgment of the investigator, is a contraindication to protocol participation or impairs a volunteer's ability to give informed consent