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
Latest Information Update: 14 Sep 2023
At a glance
- Drugs VRC-CHKVLP059-00-VP (Primary)
- Indications Chikungunya virus infections
- Focus Adverse reactions
- 08 Sep 2023 Results of a post hoc analysis comparing safety and immunogenicity of CHIKV VLP vaccine in seropositive (n = 39) versus seronegative (n = 155) vaccine recipients for 72 weeks post-vaccination published in the Vaccine
- 26 May 2021 Results published in the Media Release
- 14 Apr 2020 Results published in the JAMA: the Journal of the American Medical Association.
Most Recent Events
Trial Overview
Purpose
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.
Primary Endpoints
Number of Subjects Reporting Local 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 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).
time_frame: 7 days after any injection
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
Number of Subjects With an Abnormal Laboratory Result
description: 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.
time_frame: 4 weeks after last injection
Number of Subjects Reporting Unsolicited Adverse Events (AEs)
description: 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.
time_frame: Through study completion, an average of 72 weeks after first injection
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
Other Endpoints
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
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
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 [1]
Diseases Treated
Indication | Qualifiers | Patient Segments |
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Chikungunya virus infections | prevention | - |
Subjects
- Subject Type patients
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Number
Planned: 400
Actual: 400
- Sex male & female
- Age Group 18-60 years (Mean age = 35 years); adult
Patient 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
Patient 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
Trial Details
Identifiers
Identifier | Owner |
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NCT02562482 | ClinicalTrials.gov: US National Institutes of Health |
EudraCT2015-003556-44 | European Clinical Trials Database |
VRC704 | - |
IMEA048 | - |
Organisations
- Affiliations Leidos Holdings; The EMMES Corporation
Trial Dates
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Initiation Dates
Actual : 18 Nov 2015
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Primary Completion Dates
Planned : 01 Oct 2018
Actual : 06 Mar 2018
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End Dates
Planned : 01 Oct 2018
Actual : 06 Mar 2018
Other Details
- Design double-blind; multicentre; parallel; prospective; randomised
- Phase of Trial Phase II
- Location Dominican Republic; France; Guadeloupe; Haiti; Martinique; Puerto Rico
- Focus Adverse reactions
Interventions
Drugs | Route | Formulation |
---|---|---|
VRC-CHKVLP059-00-VPPrimary Drug | Intramuscular | Injection |
Group 1: VRC-CHKVLP059-00-VP 20 mcg
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). Biological: VRC-CHKVLP059-00-VP (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).)
Group 2: Placebo (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). Other: VRC-PBSPLA043-00-VP (VRC-PBSPLA043-00-VP, a sterile phosphate buffered saline (PBS) is the placebo for the CHIKV VLP vaccine.)
Results
Publications
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Chen GL, Coates EE, Plummer SH, Carter CA, Berkowitz N, Conan-Cibotti M, et al. Effect of a Chikungunya Virus-Like Particle Vaccine on Safety and Tolerability Outcomes: A Randomized Clinical Trial. JAMA 2020;323(14):1369-1377.
PubMed | CrossRef Fulltext -
McCarty JM, Bedell L, Mendy J, Coates EE, Chen GL, Ledgerwood JE, et al. Chikungunya virus virus-like particle vaccine is well tolerated and immunogenic in chikungunya seropositive individuals. . Vaccine 2023;.
PubMed | CrossRef Fulltext
Trial Centres
Investigators
Investigator | Centre Name | Trial Centre Country |
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Andre Cabie, MD | Clinical Investigation Center of French West Indies and French Guiana | Martinique |
Bruno Hoen, MD | University Hospital Pointe-a-Pitre, Guadeloupe |
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Clemente Diaz, MD | Puerto Rico Clinical and Translational Reserach Consortium |
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Jean W Pape, MD | GHESKIO, Haiti |
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Julie Ledgerwood, DO | VRC, NIAID, NIH |
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Midnela Acevedo-Flores, MD | San Juan Hospital |
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Study coordinator
Hopital Bichat Claude Bernard 46 rue Henri Huchard PARIS Postcode: 75018 France Telephone: 33140256365 Fax: 33140256356 aida.benalycherif@gmail.com |
IMEA Fondation Leon Mba | France |
Yeycy Donastorg, MD | Instituto Dermatológico y Cirugía de Piel | Dominican-Republic |
Centres
Centre Name | Location | Trial Centre Country |
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Centres GHESKIO | Port Au Prince | Haiti |
Clinical Investigation Center of French West Indies and French Guiana | Fort-de-France | Martinique |
FHI 360 |
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GHESKIO, Haiti |
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IMEA Fondation Leon Mba | PARIS | France |
Instituto Dermatológico y Cirugía de Piel | Santo Domingo | Dominican-Republic |
Leidos |
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National Institute of Allergy and Infectious Diseases (NIAID) |
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Puerto Rico Clinical and Translational Research Consortium | San Juan | Puerto-Rico |
Puerto Rico Clinical and Translational Reserach Consortium |
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San Juan Hospital |
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San Juan Hospital, Research Unit | Rio Piedras | Puerto-Rico |
The EMMES Corporation |
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University Hospital of Pointe-à-Pitre | Pointe A Pitre | Guadeloupe |
University Hospital Pointe-a-Pitre, Guadeloupe |
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VRC, NIAID, NIH |
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Trial History
Event Date | Event Type | Comment |
---|---|---|
08 Sep 2023 | Results | Results of a post hoc analysis comparing safety and immunogenicity of CHIKV VLP vaccine in seropositive (n = 39) versus seronegative (n = 155) vaccine recipients for 72 weeks post-vaccination published in the Vaccine Updated 14 Sep 2023 |
26 May 2021 | Results | Results published in the Media Release Updated 31 May 2021 |
29 Oct 2020 | Other trial event | Last checked against ClinicalTrials.gov record. Updated 29 Oct 2020 |
14 Apr 2020 | Results | Results published in the JAMA: the Journal of the American Medical Association. Updated 17 Apr 2020 |
25 Apr 2019 | Status change - completed | Status changed from active, no longer recruiting to completed. Updated 15 May 2019 |
27 Feb 2019 | Other trial event | New source identified and integrated (European Clinical Trials Database: EudraCT2015-003556-44). Updated 27 Feb 2019 |
15 Jun 2018 | Completion date | Planned End Date changed from 1 Dec 2017 to 1 Oct 2018. Updated 25 Jun 2018 |
15 Jun 2018 | Other trial event | Planned primary completion date changed from 1 Sep 2017 to 1 Oct 2018. Updated 25 Jun 2018 |
18 Jan 2017 | New trial record | New trial record Updated 18 Jan 2017 |
23 Oct 2016 | Status change - active, no longer recruiting | Status has been changed from Recruiting to Active, no longer recruiting. Updated 20 Jan 2017 |
References
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ClinicalTrials.gov: US National Institutes of Health. Trial-Reg 2023;.
Available from: URL: http://clinicaltrials.gov -
European Clinical Trials Database. Trial-Reg 2023;.
Available from: URL: https://www.clinicaltrialsregister.eu -
Chen GL, Coates EE, Plummer SH, Carter CA, Berkowitz N, Conan-Cibotti M, et al. Effect of a Chikungunya Virus-Like Particle Vaccine on Safety and Tolerability Outcomes: A Randomized Clinical Trial. JAMA 2020;323(14):1369-1377.
PubMed | CrossRef Fulltext -
McCarty JM, Bedell L, Mendy J, Coates EE, Chen GL, Ledgerwood JE, et al. Chikungunya virus virus-like particle vaccine is well tolerated and immunogenic in chikungunya seropositive individuals. . Vaccine 2023;.
PubMed | CrossRef Fulltext
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