Evaluating the Safety and Immune Response to a Dengue Virus Vaccine in Healthy Adults

NCT01931176 | Completed Phase 1 DMC

• 1 other identifier: CIR 286
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

Dengue viruses can cause dengue fever and other more serious illnesses. The purpose of this study is to evaluate the safety and immune response to a dengue virus vaccine.

Conditions

Dengue

Outcome Measures

Primary Outcomes (5)

• Safety of rDEN2Δ30-7169 vaccine as assessed by the frequency of vaccine-related adverse events (AEs)

  AEs are classified by both severity and seriousness, through active and passive surveillance.

  Measured through participants' last study visit at Day 180

• Frequency, quantity, and duration of viremia following vaccination

  Subjects will have samples assayed for vaccine virus on Study Days 0, 2, 4, 6, 8, 10, 12, 14, and 16. Serum will be serially diluted and the titer of vaccine virus determined.

  Measured through participants' last study visit at Day 180

• Immune response of the vaccine at 4 and 8 weeks post-vaccination

  Seropositivity to DENV-2 is defined as PRNT50 ≥ 1:10. Seroconversion is defined as a ≥ 4-fold rise in PRNT50 to wt DENV-2 Tonga/74 by Study Day 56.

  Measured at 4 and 8 weeks post-vaccination

• Titer of virus vaccine

  The peak titer, day of onset, and duration of viremia will be calculated for each subject within the vaccinated group.

  Measured through participants' last study visit at Day 180

• Number of vaccinees who seroconvert to DENV-2 by study Day 56

  Seroconversion will be defined as a ≥ 4-fold rise in PRNT50 to wt DENV-2 Tonga/74 by Study Day 56.

  Measured through Day 56

Secondary Outcomes (3)

• Number of vaccinees infected with rDEN2Δ30-7169 vaccine

  Measured through participants' last study visit at Day 180

• Comparison of infectivity rates, safety, and immunogenicity of a single dose of rDEN2Δ30 vaccine with the reported infectivity and safety of rDEN2/4Δ30 from previous clinical trials

  Measured through participants' last study visit at Day 180

• Durability of neutralizing antibody by measuring serum neutralizing antibody to DENV-2 out to 180 days after vaccination

  Measured through participants' last study visit at Day 180

Study Arms (2)

rDEN2Δ30-7169 vaccine

EXPERIMENTAL

Participants will receive a single injection of the rDEN2Δ30-7169 vaccine at study entry.

Biological: rDEN2Δ30-7169 vaccine

Placebo

PLACEBO COMPARATOR

Participants will receive a single injection of placebo at study entry.

Biological: Placebo

Interventions

rDEN2Δ30-7169 vaccine BIOLOGICAL

Administered at a dose of 10\^3 plaque-forming units (PFU); delivered by subcutaneous injection in the deltoid region of the upper arm

rDEN2Δ30-7169 vaccine

Placebo BIOLOGICAL

Delivered by subcutaneous injection in the deltoid region of the upper arm

Placebo

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Good general health as determined by physical examination, laboratory screening, and review of medical history
• Available for the duration of the study, approximately 26 weeks post vaccination
• Willingness to participate in the study as evidenced by signing the informed consent document
• Female participants of childbearing potential willing to use effective contraception for the duration of the trial. More information on this criterion can be found in the protocol.

You may not qualify if:

• Currently pregnant, as determined by positive beta-human chorionic gonadotropin (HCG) test, or breastfeeding
• Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic, rheumatologic, autoimmune, or renal disease by history, physical examination, and/or laboratory studies
• Behavioral, cognitive, or psychiatric disease that in the opinion of the investigator affects the ability of the participant to understand and cooperate with the requirements of the study protocol
• Confirmed screening laboratory values of Grade 1 or above for absolute neutrophil count (ANC), alanine aminotransferase (ALT), and serum creatinine, as defined in the protocol. Confirmation will be obtained by repeating the test to ensure the abnormal value was not due to aberrancy.
• Any other condition that in the opinion of the investigator would jeopardize the safety or rights of a participant in the trial or would render the participant unable to comply with the protocol
• Any significant alcohol or drug abuse in the past 12 months which has caused medical, occupational, or family problems, as indicated by participant history
• History of a severe allergic reaction or anaphylaxis
• Severe asthma (emergency room visit or hospitalization within the last 6 months)
• HIV infection, by screening and confirmatory assays
• Hepatitis C virus (HCV) infection, by screening and confirmatory assays
• Hepatitis B virus (HBV) infection, by hepatitis B surface antigen (HBsAg) screening
• Any known immunodeficiency syndrome
• Use of anticoagulant medications
• Use of corticosteroids (excluding topical or nasal) or immunosuppressive drugs within 28 days prior to or following vaccination. Immunosuppressive dose of corticosteroids is defined as greater than or equal to 10 mg prednisone equivalent per day for greater than or equal to 14 days.
• Receipt of a live vaccine within 28 days or a killed vaccine within the 14 days prior to vaccination or anticipated receipt of any vaccine during the 28 days following vaccination

Sponsors & Collaborators

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

Study Sites (1)

John Hopkins Bloomberg School of Public Health - Center for Immunization Research (CIR)

Baltimore, Maryland, 21205, United States

Location

Related Publications (1)

• Larsen CP, Whitehead SS, Durbin AP. Dengue human infection models to advance dengue vaccine development. Vaccine. 2015 Dec 10;33(50):7075-82. doi: 10.1016/j.vaccine.2015.09.052. Epub 2015 Sep 28.

  PMID: 26424605 DERIVED

MeSH Terms

Conditions

Dengue

Condition Hierarchy (Ancestors)

Mosquito-Borne Diseases; Vector Borne Diseases; Infections; Arbovirus Infections; Virus Diseases; Flavivirus Infections; Flaviviridae Infections; RNA Virus Infections; Hemorrhagic Fevers, Viral

Study Officials

• Anna Durbin, MD

  Center for Immunization Research (CIR), Johns Hopkins School of Public Health

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 26, 2013
• First Posted: August 29, 2013
• Study Start: June 1, 2013
• Primary Completion: December 1, 2014
• Study Completion: May 1, 2015
• Last Updated: December 15, 2015

Record last verified: 2015-12

Locations

US (1)