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

NCT02562482 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: VRC 704
• Study Type: interventional
• Target: 400
• Locations: 5 countries
• Sites: 6

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.

Conditions

Chikungunya Virus Infection

Keywords

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

Outcome Measures

Primary Outcomes (6)

• 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).

  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).

  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.

  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.

  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.

  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.

  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

  Week 8

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

  Week 8

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

  4 weeks after last study injection

Study Arms (2)

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).

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).

Other: VRC-PBSPLA043-00-VP

Interventions

VRC-CHKVLP059-00-VP BIOLOGICAL

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 1: VRC-CHKVLP059-00-VP 20 mcg

VRC-PBSPLA043-00-VP OTHER

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

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

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• A subject must meet all of the following criteria:
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (6)

Instituto Dermatológico y Cirugía de Piel

Santo Domingo, Dominican Republic

Location

University Hospital of Pointe-à-Pitre

Pointe-à-Pitre, Guadeloupe

Location

Centres GHESKIO

Port-au-Prince, Haiti

Location

Centre Hospitalier Universitaire (CHU), Martinique

Fort-de-France, 0596 55 20 00, Martinique

Location

San Juan Hospital, Research Unit

Rio Piedras, 00935, Puerto Rico

Location

Puerto Rico Clinical and Translational Research Consortium

San Juan, 00936-5067, Puerto Rico

Location

Related Publications (5)

• 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.

  PMID: 25132507 BACKGROUND

• 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.

  PMID: 26132956 BACKGROUND

• 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.

  PMID: 17698645 BACKGROUND

• 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.

  PMID: 32286643 RESULT

• McCarty 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.

  PMID: 37690874 DERIVED

MeSH Terms

Conditions

Chikungunya Fever

Condition Hierarchy (Ancestors)

Alphavirus Infections; Arbovirus Infections; Vector Borne Diseases; Infections; Mosquito-Borne Diseases; Virus Diseases; Togaviridae Infections; RNA Virus Infections

Limitations and Caveats

Exploratory immunogenicity analyses (to evaluate humoral and cellular responses to VRC-CHKVLP059-00-VP at additional time points by antibody assays that include antigen-specific ELISA and neutralization assay) were not completed and are not reported.

Results Point of Contact

• Title: Dr. Grace Chen, Deputy Chief, Clinical Trials Program, Vaccine Research Center
• Organization: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health

grace.chen@nih.gov

240-669-2809

Study Officials

• Nicolas Rosario, MD

  San Juan Hospital

  PRINCIPAL INVESTIGATOR

• Clemente Diaz, MD

  Puerto Rico Clinical and Translational Research Consortium

  PRINCIPAL INVESTIGATOR

• Bruno Hoen, MD

  University Hospital Pointe-a-Pitre, Guadeloupe

  PRINCIPAL INVESTIGATOR

• Yeycy Donastorg, MD

  Instituto Dermatológico y Cirugía de Piel

  PRINCIPAL INVESTIGATOR

• Jean W Pape, MD

  Centres GHESKIO, Haiti

  PRINCIPAL INVESTIGATOR

• Andre Cabie, MD

  Centre Hospitalier Universitaire (CHU), Martinique

  PRINCIPAL INVESTIGATOR

• Julie Ledgerwood, DO

  VRC, NIAID, NIH

  STUDY CHAIR

• Grace Chen, MD

  VRC, NIAID, NIH

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 21, 2015
• First Posted: September 29, 2015
• Study Start: November 18, 2015
• Primary Completion: March 6, 2018
• Study Completion: March 6, 2018
• Last Updated: October 22, 2020
• Results First Posted: May 14, 2019

Record last verified: 2020-10

Data Sharing

• IPD Sharing: Will not share

Locations

GU (1); MA (1); PR (2); HA (1); DO (1)