Chikungunya Virus InfectionPhase 2NCT02562482
Trial for Safety and Immunogenicity of a Chikungunya Vaccine, VRC-CHKVLP059-00-VP, in Healthy Adults
A Phase 2 study testing VRC-CHKVLP059-00-VP and VRC-PBSPLA043-00-VP in people with Chikungunya Virus Infection, run by National Institute of Allergy and Infectious Diseases (NIAID) at 6 sites in 5 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Chikungunya Virus Infection
- What is being tested?
- VRC-CHKVLP059-00-VP and VRC-PBSPLA043-00-VP
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 400 participants
- Where
- 6 sitesin 5 countries
- Study dates
- 18 Nov 2015to 6 Mar 2018
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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 locations and contacts
6 sites in 5 countries.
6 sites in 5 countries
Puerto Rico2 sites
San Juan Hospital, Research Unit
Rio Piedras, 00935
Puerto Rico Clinical and Translational Research Consortium
San Juan, 00936-5067
Dominican Republic1 site
Instituto Dermatológico y Cirugía de Piel
Santo Domingo
Martinique1 site
Centre Hospitalier Universitaire (CHU), Martinique
Fort-de-France, 0596 55 20 00
About this study
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
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.
Read the 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.
- Conditions
- Chikungunya Virus Infection
- Being tested
- VRC-CHKVLP059-00-VP, VRC-PBSPLA043-00-VP
- Keywords
- Antibody Response, Immune Response, Healthy Volunteer, Vaccine-Mediated Protection, Chikungunya Virus, Vaccines, Virus-like Particles
- Medical subject headings
- Chikungunya Fever
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VRC-CHKVLP059-00-VPBiological
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).
VRC-PBSPLA043-00-VPOther
VRC-PBSPLA043-00-VP, a sterile phosphate buffered saline (PBS) is the placebo for the CHIKV VLP vaccine.
| Study group | Role | What they receive |
|---|---|---|
| Group 1: VRC-CHKVLP059-00-VP 20 mcg | Experimental | 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). Receives: Biological: VRC-CHKVLP059-00-VP |
| Group 2: Placebo (VRC-PBSPLA043-00-VP) | Placebo comparator | 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). Receives: Other: VRC-PBSPLA043-00-VP |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 7 days after any injection
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).
Measured: 7 days after any injection
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.
Measured: 4 weeks after last injection
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.
Measured: Through study completion, an average of 72 weeks after first injection
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.
Measured: Through study completion, an average of 72 weeks after first injection
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.
Measured: Through study completion, an average of 72 weeks after first injection
Secondary outcomes (3)
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.
Measured: Week 8
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.
Measured: Week 8
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.
Measured: 4 weeks after last study injection
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Sep 2015 (estimated)
- Study start18 Nov 2015
- Primary completion6 Mar 2018
- Study completion6 Mar 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Chikungunya Virus InfectionStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 400 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Nicolas Rosario, MD, Principal investigator, San Juan HospitalClemente Diaz, MD, Principal investigator, Puerto Rico Clinical and Translational Research ConsortiumBruno Hoen, MD, Principal investigator, University Hospital Pointe-a-Pitre, GuadeloupeYeycy Donastorg, MD, Principal investigator, Instituto Dermatológico y Cirugía de PielJean W Pape, MD, Principal investigator, Centres GHESKIO, HaitiAndre Cabie, MD, Principal investigator, Centre Hospitalier Universitaire (CHU), MartiniqueJulie Ledgerwood, DO, Study chair, VRC, NIAID, NIHGrace Chen, MD, Study chair, VRC, NIAID, NIH
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02562482
- Sponsor's protocol ID
- VRC 704
- Status last verified
- Oct 2020
- First submitted
- 21 Sep 2015
- Last updated
- 22 Oct 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Chang LJ, Dowd KA, Mendoza FH, Saunders JG, Sitar S, Plummer SH, Yamshchikov G, Sarwar UN, Hu Z, Enama ME, Bailer RT, Koup RA, Schwartz RM, Akahata W, Nabel GJ, Mascola JR, Pierson TC, Graham BS, Ledgerwood JE; VRC 311 Study Team. Safety and tolerability of chikungunya virus-like particle vaccine in healthy adults: a phase 1 dose-escalation trial. Lancet. 2014 Dec 6;384(9959):2046-52. doi: 10.1016/S0140-6736(14)61185-5. Epub 2014 Aug 14.
PubMed 25132507Weaver SC, Lecuit M. Chikungunya Virus Infections. N Engl J Med. 2015 Jul 2;373(1):94-5. doi: 10.1056/NEJMc1505501. No abstract available.
PubMed 26132956Powers AM, Logue CH. Changing patterns of chikungunya virus: re-emergence of a zoonotic arbovirus. J Gen Virol. 2007 Sep;88(Pt 9):2363-2377. doi: 10.1099/vir.0.82858-0. No abstract available.
PubMed 17698645Chen GL, Coates EE, Plummer SH, Carter CA, Berkowitz N, Conan-Cibotti M, Cox JH, Beck A, O'Callahan M, Andrews C, Gordon IJ, Larkin B, Lampley R, Kaltovich F, Gall J, Carlton K, Mendy J, Haney D, May J, Bray A, Bailer RT, Dowd KA, Brockett B, Gordon D, Koup RA, Schwartz R, Mascola JR, Graham BS, Pierson TC, Donastorg Y, Rosario N, Pape JW, Hoen B, Cabie A, Diaz C, Ledgerwood JE; VRC 704 Study Team. Effect of a Chikungunya Virus-Like Particle Vaccine on Safety and Tolerability Outcomes: A Randomized Clinical Trial. JAMA. 2020 Apr 14;323(14):1369-1377. doi: 10.1001/jama.2020.2477.
PubMed 32286643McCarty JM, Bedell L, Mendy J, Coates EE, Chen GL, Ledgerwood JE, Tredo SR, Warfield KL, Richardson JS. Chikungunya virus virus-like particle vaccine is well tolerated and immunogenic in chikungunya seropositive individuals. Vaccine. 2023 Oct 6;41(42):6146-6149. doi: 10.1016/j.vaccine.2023.08.086. Epub 2023 Sep 9.
PubMed 37690874