Back to results

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

Primary Purpose

Chikungunya Virus Infection

Status

Completed

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

VRC-CHKVLP059-00-VP

VRC-PBSPLA043-00-VP

About this trial

This is an interventional prevention trial for Chikungunya Virus Infection focused on measuring Antibody Response, Immune Response, Healthy Volunteer, Vaccine-Mediated Protection, Chikungunya Virus, Vaccines, Virus-like Particles

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

Instituto Dermatológico y Cirugía de Piel
University Hospital of Pointe-à-Pitre
Centres GHESKIO
Centre Hospitalier Universitaire (CHU), Martinique
San Juan Hospital, Research Unit
Puerto Rico Clinical and Translational Research Consortium

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Group 1: VRC-CHKVLP059-00-VP 20 mcg

Group 2: Placebo (VRC-PBSPLA043-00-VP)

Arm Description

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 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).

Outcomes

Primary Outcome Measures

Number of Subjects Reporting Local Reactogenicity Signs and Symptoms Within 7 Days of 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 Systemic Reactogenicity Signs and Symptoms Within 7 Days of 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

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.

Number of Subjects Reporting Unsolicited Adverse Events (AEs)

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 Reporting Serious Adverse Events (SAEs)

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 With Confirmed Chikungunya Virus (CHIKV) Infection Events

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.

Secondary Outcome Measures

Chikungunya Antigen-specific Neutralizing Antibody Geometric Mean Titer (GMT) - Per Protocol Population

Antibody responses as measured by neutralization antibody (NAb) assay 4 weeks after last study injection.

Chikungunya Antigen-specific Neutralizing Antibody Geometric Mean Titer (GMT) - Intent-to-Treat Population

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

Antibody responses as measured by neutralization antibody (NAb) assay 4 weeks after last study injection.

Full Information

NCT ID

NCT02562482

First Posted

September 21, 2015

Last Updated

October 20, 2020

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

1. Study Identification

Unique Protocol Identification Number

NCT02562482

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

October 2020

Overall Recruitment Status

Completed

Study Start Date

November 18, 2015 (Actual)

Primary Completion Date

March 6, 2018 (Actual)

Study Completion Date

March 6, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Chikungunya Virus Infection

Keywords

Antibody Response, Immune Response, Healthy Volunteer, Vaccine-Mediated Protection, Chikungunya Virus, Vaccines, Virus-like Particles

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

400 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Group 1: VRC-CHKVLP059-00-VP 20 mcg

Arm Type

Experimental

Arm Description

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).

Arm Title

Group 2: Placebo (VRC-PBSPLA043-00-VP)

Arm Type

Placebo Comparator

Arm Description

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).

Intervention Type

Biological

Intervention Name(s)

VRC-CHKVLP059-00-VP

Intervention Description

VRC-CHKVLP059-00-VP is a virus-like particle (VLP) vaccine that consists of CHIKV VLP composed of E1, E2 and capsid proteins of the CHIKV (strain 37997).

Intervention Type

Other

Intervention Name(s)

VRC-PBSPLA043-00-VP

Intervention Description

VRC-PBSPLA043-00-VP, a sterile phosphate buffered saline (PBS) is the placebo for the CHIKV VLP vaccine.

Primary Outcome Measure Information:

Title

Number of Subjects Reporting Local Reactogenicity Signs and Symptoms Within 7 Days of Any Injection

Description

Time Frame

7 days after any injection

Title

Number of Subjects Reporting Systemic Reactogenicity Signs and Symptoms Within 7 Days of Any Injection

Description

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).

Time Frame

7 days after any injection

Title

Number of Subjects With an Abnormal Laboratory Result

Description

Time Frame

4 weeks after last injection

Title

Number of Subjects Reporting Unsolicited Adverse Events (AEs)

Description

Time Frame

Through study completion, an average of 72 weeks after first injection

Title

Number of Subjects Reporting Serious Adverse Events (SAEs)

Description

Time Frame

Through study completion, an average of 72 weeks after first injection

Title

Number of Subjects With Confirmed Chikungunya Virus (CHIKV) Infection Events

Description

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.

Time Frame

Through study completion, an average of 72 weeks after first injection

Secondary Outcome Measure Information:

Title

Chikungunya Antigen-specific Neutralizing Antibody Geometric Mean Titer (GMT) - Per Protocol Population

Description

Antibody responses as measured by neutralization antibody (NAb) assay 4 weeks after last study injection.

Time Frame

Week 8

Title

Chikungunya Antigen-specific Neutralizing Antibody Geometric Mean Titer (GMT) - Intent-to-Treat Population

Description

Antibody responses as measured by neutralization antibody (NAb) assay 4 weeks after last study injection.

Time Frame

Week 8

Title

Chikungunya Antigen-specific Neutralizing Antibody Geometric Mean Titer (GMT) - Modified Intent-to-Treat

Description

Antibody responses as measured by neutralization antibody (NAb) assay 4 weeks after last study injection.

Time Frame

4 weeks after last study injection

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

60 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials: