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

Phase 2

Completed

Conditions: Chikungunya Virus Infection

Interventions: Biological: VRC-CHKVLP059-00-VP
Other: VRC-PBSPLA043-00-VP

Registration Number: NCT02562482

Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Brief Summary: 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.

Detailed Description: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 400

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group 1: VRC-CHKVLP059-00-VP 20 mcg	VRC-CHKVLP059-00-VP	Group 1 subjects were randomized to receive two intramuscular (IM) injections of CHIKV VLP vaccine (VRC-CHKVLP059-00-VP) at Day 0 and Day 28 (+14 days) at a dose of 20 micrograms (mcg).
Group 2: Placebo (VRC-PBSPLA043-00-VP)	VRC-PBSPLA043-00-VP	Group 2 subjects were randomized to receive two intramuscular (IM) injections of Phosphate Buffered Saline (VRC-PBSPLA043-00-VP) placebo at Day 0 and Day 28 (+14 days).

Primary Outcome Measures

Name	Time	Method
Number of Subjects Reporting Unsolicited Adverse Events (AEs)	Through study completion, an average of 72 weeks after first injection	Unsolicited AEs were reported from receipt of first study injection through 4 weeks after the last study injection administered. After the indicated time period through the last expected study visit at 72 weeks, only new chronic medical conditions and SAEs (reported as a separate outcome and in the AE module) were collected as unsolicited AEs. A subject with multiple experiences of the same event is counted once using the event of worst severity. The number reported for "Any AE" is the number of subjects reporting at least one or more AEs.
Number of Subjects With Confirmed Chikungunya Virus (CHIKV) Infection Events	Through study completion, an average of 72 weeks after first injection	Confirmed Chikungunya infections by positive polymerase chain reaction (PCR) results reported from receipt of first study injection through the last expected study visit at 72 weeks.
Number of Subjects Reporting Local Reactogenicity Signs and Symptoms Within 7 Days of Any Injection	7 days after any injection	Subjects recorded the occurrence of solicited symptoms on a memory aid for 7 days after any injection and reviewed the memory aid with clinic staff at a follow up visit. Subjects are counted once for each symptom at the worst severity if they indicated experiencing the symptom at any severity during the reporting period. The number reported for "Any Local Symptom" is the number of subjects reporting any local symptom at the worst severity. Solicited reactogenicity was recorded without an attribution assessment. Grading (Mild, Moderate, Severe) was done using the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials (FDA Guidance - September 2007).
Number of Subjects Reporting Serious Adverse Events (SAEs)	Through study completion, an average of 72 weeks after first injection	SAEs were reported from receipt of first study injection through the last expected study visit at 72 weeks. Grading (Mild, Moderate, Severe, Life-threatening, and Death) was done using the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials (FDA Guidance - September 2007). The relationship between a SAE and the study product was assessed by the investigator on the basis of his or her clinical judgment and the definitions outlined in the protocol. A subject with multiple SAEs is counted only once.
Number of Subjects Reporting Systemic Reactogenicity Signs and Symptoms Within 7 Days of Any Injection	7 days after any injection	Subjects recorded the occurrence of solicited symptoms on a memory aid for 7 days after any injection and reviewed the memory aid with clinic staff at a follow up visit. Subjects are counted once for each symptom at the worst severity if they indicated experiencing the symptom at any severity during the reporting period. The number reported for "Any Systemic Symptom" is the number of subjects reporting any systemic symptom at the worst severity. Solicited reactogenicity was recorded without an attribution assessment. Grading (Mild, Moderate, Severe) was done using the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials (FDA Guidance - September 2007).
Number of Subjects With an Abnormal Laboratory Result	4 weeks after last injection	Safety laboratory parameters included hematology (hemoglobin, hematocrit, platelets, red blood cell (RBC), white blood cell (WBC), neutrophil, monocyte, lymphocyte, basophil and eosinophil counts, mean corpuscular volume (MCV)) and chemistry (ALT). Complete blood count, differential, platelet and ALT results were collected at screening (≤ 56 days before enrollment), Day 0 prior to study product administration (baseline), and Days 28 and 56.

Secondary Outcome Measures

Name	Time	Method
Chikungunya Antigen-specific Neutralizing Antibody Geometric Mean Titer (GMT) - Intent-to-Treat Population	Week 8	Antibody responses as measured by neutralization antibody (NAb) assay 4 weeks after last study injection.
Chikungunya Antigen-specific Neutralizing Antibody Geometric Mean Titer (GMT) - Per Protocol Population	Week 8	Antibody responses as measured by neutralization antibody (NAb) assay 4 weeks after last study injection.
Chikungunya Antigen-specific Neutralizing Antibody Geometric Mean Titer (GMT) - Modified Intent-to-Treat	4 weeks after last study injection	Antibody responses as measured by neutralization antibody (NAb) assay 4 weeks after last study injection.

Trial Locations

Locations (6): Puerto Rico Clinical and Translational Research Consortium
🇵🇷
San Juan, Puerto Rico
Centres GHESKIO
🇭🇹
Port Au Prince, Haiti
Centre Hospitalier Universitaire (CHU), Martinique
🇲🇶
Fort-de-France, Martinique
San Juan Hospital, Research Unit
🇵🇷
Rio Piedras, Puerto Rico
Instituto Dermatológico y Cirugía de Piel
🇩🇴
Santo Domingo, Dominican Republic
University Hospital of Pointe-à-Pitre
🇬🇵
Pointe-à-Pitre, Guadeloupe