Clinical trial NCT01489358: Chikungunya Virus Vaccine Trial in Healthy Adults
Official title: VRC 311: A Phase 1 Open Label, Dose-Escalation Clinical Trial to Evaluate the Safety and Immunogenicity of a Virus-Like Particle (VLP) Chikungunya Vaccine, VRC-CHKVLP059-00-VP, in Healthy Adults
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Viral Vaccines
Chikungunya Fever
Chikungunya Virus Infection
Keywords: Vaccine-Mediated Protection
Antibody Response
Chikungunya Virus
Immune Response
Healthy Volunteer
Humoral Inmunity
Virus-like Particles
Lead sponsor: National Institutes of Health Clinical Center (CC)
Sponsor class: NIH
First posted: 2011-12-09
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Background:

- Chikungunya virus (CHIKV) is transmitted by mosquitoes. It can cause fever, headache, muscle pain, fatigue, and joint pain. The disease usually does not cause death. But the joint pain, which may be directly related to the infecting virus, may be severe and last for several months. CHIKV outbreaks are most common in Africa, India, and Asia. A new experimental vaccine for CHIKV has been developed, and researchers are testing it in healthy adults. Participants cannot develop CHIKV from this vaccine.

Objectives:

- To test the safety and effectiveness of a Chikungunya virus vaccine.

Eligibility:

- Healthy individuals between 18 and 50 years of age.

Design:

* This study, including vaccine doses and followup tests, will last about 44 weeks. Participants will have three vaccination visits, six followup clinic visits, and three telephone contacts during this study. Vaccination visits will take about 4 hours. Most other clinic visits will usually take 2 hours. The telephone contacts will take about 15 minutes.
* Participants will be screened with a physical exam and medical history. Blood samples will also be collected.
* Participants will be assigned to one of three dose groups. Information about doses will be provided before the start of the vaccinations.
* Vaccine injections will be given at the start of the study, at 4 weeks, and at 20 weeks. Participants will be asked to keep an eye on the injection site for 7 days and to notify researchers if there are any side effects.
* Participants will be monitored throughout the study with blood samples and clinic visits.

Detailed description: This is a Phase I, open-label, dose-escalation study to examine the safety, tolerability, and immune response to a Virus-Like Particle (VLP) Chikungunya Virus (CHIKV) vaccine in healthy adults ages 18 to 50 years old. The plan is for 25 subjects to receive 3 intramuscular vaccine injections at weeks 0, 4, and 20. The three groups will be enrolled sequentially starting with the lowest dose of 10 micrograms per injection in Group 1.

The hypothesis is that the vaccine is safe and induces immune responses to CHIKV. The primary objective is to evaluate the safety and tolerability of the investigational vaccine, VRC-CHKVLP059-00-VP, at three dosages, 10 micrograms (mcg), 20 mcg, and 40 mcg, in healthy adults. The secondary objective is to evaluate the antibody response against CHIKV VLPs four weeks after the third vaccine injection. The exploratory objectives relate to antigen-specific humoral and cellular immune responses throughout the study.

Eligibility criteria: INCLUSION CRITERIA:

A participant must meet all of the following criteria:

1. 18 to 50 years old
2. Available for clinical follow-up through Week 44
3. Able to provide proof of identity to the satisfaction of the study clinician completing the enrollment process
4. Complete an Assessment of Understanding prior to enrollment and verbalize understanding of all questions answered incorrectly
5. Able and willing to complete the informed consent process
6. Willing to donate blood for sample storage to be used for future research
7. In good general health, with a BMI less than or equal to 40, without clinically significant medical history, and has satisfactorily completed screening
8. Physical examination and laboratory results without clinically significant findings within the 56 days prior to enrollment

   Laboratory Criteria within 56 days prior to enrollment:
9. Hemoglobin greater than or equal to11.5 g/dL for women; greater than or equal to13.5 g/dL for men
10. WBC: 3,000-12,000 cells/mm(3).
11. Differential either within institutional normal range or accompanied by physician approval
12. Total lymphocyte count: greater than or equal to 800 cells/mm(3)
13. Platelets = 125,000-500,000/mm(3)
14. Alanine aminotransferase (ALT) less than or equal to 1.25 times upper limit of normal range
15. Serum creatinine less than or equal to1x upper limit of normal (less than or equal to1.3 mg/dL for females; less than or equal to1.4 mg/dL for males).
16. Negative FDA-approved HIV blood test

    Female-Specific Criteria
17. Negative Beta-HCG pregnancy test (urine or serum) on day of enrollment for women presumed to be of reproductive potential
18. A woman of childbearing potential must agree to use an effective means of birth control from at least 21 days prior to enrollment through 12 weeks after last study vaccination

EXCLUSION CRITERIA:

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

Female-Specific Criteria

1. Woman who is breast-feeding or planning to become pregnant during the time projected for individual study participation
2. Systemic immunosuppressive medications or cytotoxic medications within 12 weeks prior to enrollment \[with the exceptions that a short course of corticosteroids (less than or equal to10 days duration or a single injection) for a self-limited condition at least 2 weeks prior to enrollment will not exclude study participation\]
3. Blood products within 16 weeks prior to enrollment
4. Immunoglobulin within 8 weeks prior to enrollment
5. Prior vaccinations with an investigational CHIKV vaccine
6. Investigational research agents within 4 weeks prior to enrollment
7. Live attenuated vaccines within 4 weeks prior to enrollment
8. Medically indicated subunit or killed vaccines, e.g. influenza, pneumococcal, or allergy treatment with antigen injections, within 2 weeks prior to enrollment
9. Current anti-TB prophylaxis or therapy

   Subject has a history of any of the following clinically significant conditions:
10. A history of confirmed or suspected CHIKV infection
11. A history of immune-mediated or clinically significant arthritis
12. Serious reactions to vaccines that preclude receipt of study vaccinations as determined by the investigator
13. Hereditary angioedema (HAE), acquired angioedema (AAE), or idiopathic forms of angioedema
14. 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
15. Diabetes mellitus (type I or II), with the exception of gestational diabetes
16. Idiopathic urticaria within the past year
17. Bleeding disorder diagnosed by a doctor (e.g. factor deficiency, coagulopathy, or platelet disorder requiring special precautions) or significant bruising or bleeding difficulties with IM injections or blood draws
18. Malignancy that is active, or treated malignancy for which there is not reasonable assurance of sustained cure, or malignancy that is likely to recur during the period of the study
19. Seizure disorder other than: 1) febrile seizures, 2) seizures secondary to alcohol withdrawal more than 3 years ago, or 3) seizures that have not required treatment within the last 3 years
20. Asplenia, functional asplenia or any condition resulting in the absence or removal of the spleen
21. Psychiatric condition that may preclude compliance with the protocol; past or present psychoses; disorder requiring lithium; or within five years prior to enrollment, a history of suicide plan or attempt
22. Any medical condition (such as thyroid disease or hypertension that are not well controlled by medication, or viral hepatitis) that, in the judgment of the investigator, is a contraindication to protocol participation or impairs a volunteer's ability to give informed consent

Primary outcomes:
measure: Number of Subjects Reporting Local Reactogenicity Signs and Symptoms Within 7 Days of First Vaccination
timeFrame: 7 days after the first vaccination
measure: Number of Subjects Reporting Local Reactogenicity Signs and Symptoms Within 7 Days of Second Vaccination
timeFrame: 7 days after the second vaccination
measure: Number of Subjects Reporting Local Reactogenicity Signs and Symptoms Within 7 Days of Third Vaccination
timeFrame: 7 days after the third vaccination
measure: Number of Subjects Reporting Local Reactogenicity Signs and Symptoms Within 7 Days of Any Vaccination
timeFrame: 7 days after any vaccination
measure: Number of Subjects Reporting Systemic Reactogenicity Signs and Symptoms Within 7 Days of First Vaccination
timeFrame: 7 days after the first vaccination
measure: Number of Subjects Reporting Systemic Reactogenicity Signs and Symptoms Within 7 Days of Second Vaccination
timeFrame: 7 days after the second vaccination
measure: Number of Subjects Reporting Systemic Reactogenicity Signs and Symptoms Within 7 Days of Third Vaccination
timeFrame: 7 days after the third vaccination
measure: Number of Subjects Reporting Systemic Reactogenicity Signs and Symptoms Within 7 Days of Any Vaccination
timeFrame: 7 days after any vaccination
measure: Number of Subjects With an Any Abnormal Laboratory Result
timeFrame: 44 weeks after first vaccination
measure: Number of Subjects Reporting Serious Adverse Events
timeFrame: 44 weeks after first vaccination
measure: Number of Subjects Reporting 1 or More Unsolicited Adverse Event
timeFrame: 28 days after each vaccination
Secondary outcomes:
measure: Chikungunya Antigen-specific ELISA Geometric Mean Titer (GMT)
timeFrame: 24 weeks after the first vaccination
measure: Chikungunya Antigen-specific Neutralizing Antibody Geometric Mean Titer (GMT)
timeFrame: Pre-vaccination (Week 0)
measure: Chikungunya Antigen-specific Neutralizing Antibody Geometric Mean Titer (GMT)
timeFrame: 24 weeks after the first vaccination
Other outcomes:
Locations:
city: Bethesda
country: United States
facility: National Institutes of Health Clinical Center, 9000 Rockville Pike
state: Maryland
Study officials:
affiliation: National Institute of Allergy and Infectious Diseases (NIAID)
name: Julie E Ledgerwood, D.O.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Strauss JH, Strauss EG. The alphaviruses: gene expression, replication, and evolution. Microbiol Rev. 1994 Sep;58(3):491-562. doi: 10.1128/mr.58.3.491-562.1994.
citation: Powers 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.
citation: Volk SM, Chen R, Tsetsarkin KA, Adams AP, Garcia TI, Sall AA, Nasar F, Schuh AJ, Holmes EC, Higgs S, Maharaj PD, Brault AC, Weaver SC. Genome-scale phylogenetic analyses of chikungunya virus reveal independent emergences of recent epidemics and various evolutionary rates. J Virol. 2010 Jul;84(13):6497-504. doi: 10.1128/JVI.01603-09. Epub 2010 Apr 21.
citation: 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.