Clinical trial NCT02562482: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chikungunya Virus Infection
Keywords: Antibody Response
Immune Response
Healthy Volunteer
Vaccine-Mediated Protection
Chikungunya Virus
Vaccines, Virus-like Particles
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
First posted: 2015-09-29
Enrollment: 400
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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

Primary outcomes:
measure: Number of Subjects Reporting Local Reactogenicity Signs and Symptoms Within 7 Days of Any Injection
timeFrame: 7 days after any injection
measure: Number of Subjects Reporting Systemic Reactogenicity Signs and Symptoms Within 7 Days of Any Injection
timeFrame: 7 days after any injection
measure: Number of Subjects With an Abnormal Laboratory Result
timeFrame: 4 weeks after last injection
measure: Number of Subjects Reporting Unsolicited Adverse Events (AEs)
timeFrame: Through study completion, an average of 72 weeks after first injection
measure: Number of Subjects Reporting Serious Adverse Events (SAEs)
timeFrame: Through study completion, an average of 72 weeks after first injection
measure: Number of Subjects With Confirmed Chikungunya Virus (CHIKV) Infection Events
timeFrame: Through study completion, an average of 72 weeks after first injection
Secondary outcomes:
measure: Chikungunya Antigen-specific Neutralizing Antibody Geometric Mean Titer (GMT) - Per Protocol Population
timeFrame: Week 8
measure: Chikungunya Antigen-specific Neutralizing Antibody Geometric Mean Titer (GMT) - Intent-to-Treat Population
timeFrame: Week 8
measure: Chikungunya Antigen-specific Neutralizing Antibody Geometric Mean Titer (GMT) - Modified Intent-to-Treat
timeFrame: 4 weeks after last study injection
Other outcomes:
Locations:
city: Santo Domingo
country: Dominican Republic
facility: Instituto Dermatológico y Cirugía de Piel
city: Pointe-à-Pitre
country: Guadeloupe
facility: University Hospital of Pointe-à-Pitre
city: Port Au Prince
country: Haiti
facility: Centres GHESKIO
city: Fort-de-France
country: Martinique
facility: Centre Hospitalier Universitaire (CHU), Martinique
city: Rio Piedras
country: Puerto Rico
facility: San Juan Hospital, Research Unit
city: San Juan
country: Puerto Rico
facility: Puerto Rico Clinical and Translational Research Consortium
Study officials:
affiliation: San Juan Hospital
name: Nicolas Rosario, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Puerto Rico Clinical and Translational Research Consortium
name: Clemente Diaz, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospital Pointe-a-Pitre, Guadeloupe
name: Bruno Hoen, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Instituto Dermatológico y Cirugía de Piel
name: Yeycy Donastorg, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Centres GHESKIO, Haiti
name: Jean W Pape, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Centre Hospitalier Universitaire (CHU), Martinique
name: Andre Cabie, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: VRC, NIAID, NIH
name: Julie Ledgerwood, DO
role: STUDY_CHAIR
affiliation: VRC, NIAID, NIH
name: Grace Chen, MD
role: STUDY_CHAIR
References:
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.
citation: Weaver SC, Lecuit M. Chikungunya Virus Infections. N Engl J Med. 2015 Jul 2;373(1):94-5. doi: 10.1056/NEJMc1505501. No abstract available.
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: Chen 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.