Evaluation of the Safety and Immune Response of Five Admixtures of a Tetravalent Dengue Virus Vaccine

NCT01072786 | Completed Phase 1 DMC

• 1 other identifier: CIR 268
• Study Type: interventional
• Target: 141
• Locations: 1 country
• Sites: 4

Brief Summary

Dengue viruses can cause dengue fever and other serious health conditions, primarily affecting people living in tropical regions of the world. This study will evaluate the safety and immune responses of five formulations of a tetravalent dengue virus vaccine in healthy adults.

Conditions

Dengue

Keywords

Dengue Virus; Dengue Fever; Dengue Vaccine; Dengue Hemorrhagic Fever; Dengue Shock Syndrome

Outcome Measures

Primary Outcomes (4)

• Safety of five TetraVax-DV admixtures, as assessed by the frequency of vaccine-related adverse events (AEs), graded by severity

  Measured out to Day 28

• Determination of the serum plaque reduction neutralization titer 60% (PRNT_60) to DEN1, DEN2, DEN3, and DEN4 viruses

  Measured at Days 0, 28, 42, and 180

• Monovalent, bivalent, trivalent, and tetravalent seropositivity and seroconversion rates

  Measured at 4 and 6 weeks after vaccination

• Seropositivity and seroconversion rates to greater than 60% in in the TetraVax-DV admixture 5 vaccine arm

  Measured by Day 42

Secondary Outcomes (6)

• Frequency, quantity, and duration of viremia following vaccination

  Measured out to Day 21

• Number of vaccinees infected with DEN1, DEN2, DEN3, and DEN4

  Measured by Day 42

• Duration of the neutralizing antibody response

  Measured at Day 180

• Safety and immunogenicity of a second dose of vaccine given 6 months after the first dose (optional substudy)

  Measured at Day 222 (42 days after second dose)

• Seroconversion as assessed by a greater than or equal to 4-fold rise in DEN1, DEN2, DEN3, or DEN4 neutralizing antibody titers compared with the pre-vaccination antibody titer

  Measured by Day 42

Study Arms (6)

TetraVax-DV Vaccine-Admixture 1

EXPERIMENTAL

Participants will receive the TetraVax-DV admixture 1 vaccine.

Biological: TetraVax-DV Vaccine-Admixture 1

TetraVax-DV Vaccine-Admixture 2

EXPERIMENTAL

Participants will receive the TetraVax-DV admixture 2 vaccine.

Biological: TetraVax-DV Vaccine-Admixture 2

TetraVax-DV Vaccine-Admixture 3

EXPERIMENTAL

Participants will receive the TetraVax-DV admixture 3 vaccine.

Biological: TetraVax-DV Vaccine-Admixture 3

TetraVax-DV Vaccine-Admixture 4

EXPERIMENTAL

Participants will receive the TetraVax-DV admixture 4 vaccine.

Biological: TetraVax-DV Vaccine-Admixture 4

Placebo

PLACEBO COMPARATOR

Participants will receive the placebo.

Biological: Placebo

TetraVax-DV Vaccine-Admixture 5

EXPERIMENTAL

Participants will receive the TetraVax-DV admixture 5 vaccine.

Biological: TetraVax-DV Vaccine-Admixture 5

Interventions

TetraVax-DV Vaccine-Admixture 1 BIOLOGICAL

One subcutaneous injection of a recombinant live attenuated TetraVax-DV vaccine, admixture 1 (10\^3 PFU of rDEN1Δ30, 10\^3 PFU of rDEN2/4Δ30\[ME\], 10\^3 PFU of rDEN3-3´D4Δ30, 10\^3 PFU of rDEN4Δ30)

TetraVax-DV Vaccine-Admixture 1

TetraVax-DV Vaccine-Admixture 2 BIOLOGICAL

One subcutaneous injection of a recombinant live attenuated TetraVax-DV vaccine, admixture 2 (10\^3 PFU of rDEN1Δ30, 10\^3 PFU of rDEN2/4Δ30\[ME\], 10\^3 PFU of rDEN3-3´D4Δ30, 10\^3 PFU of rDEN4Δ30-200,201)

TetraVax-DV Vaccine-Admixture 2

TetraVax-DV Vaccine-Admixture 3 BIOLOGICAL

One subcutaneous injection of a recombinant live attenuated TetraVax-DV vaccine, admixture 3 (10\^3 PFU of rDEN1Δ30, 10\^3 PFU of rDEN2/4Δ30\[ME\], 10\^3 PFU of rDEN3Δ30/31-7164, 10\^3 PFU of rDEN4Δ30)

TetraVax-DV Vaccine-Admixture 3

TetraVax-DV Vaccine-Admixture 4 BIOLOGICAL

One subcutaneous injection of a recombinant live attenuated TetraVax-DV vaccine, admixture 4 (10\^3 PFU of rDEN1Δ30, 10\^3 PFU of rDEN2/4Δ30\[ME\], 10\^3 PFU of rDEN3Δ30/31-7164, 10\^3 PFU of rDEN4Δ30-200,201)

TetraVax-DV Vaccine-Admixture 4

Placebo BIOLOGICAL

One subcutaneous injection of a placebo containing vaccine diluent but no actual vaccine

Placebo

TetraVax-DV Vaccine-Admixture 5 BIOLOGICAL

One subcutaneous injection of a recombinant live attenuated TetraVax-DV vaccine, admixture 5 (10\^3 PFU of rDEN1Δ30, 10\^4 PFU of rDEN2/4Δ30(ME), 10\^3 PFU of rDEN3Δ30/31-7164, and 10\^3 PFU of rDEN4Δ30)

TetraVax-DV Vaccine-Admixture 5

Eligibility Criteria

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

You may qualify if:

• In 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
• Willing to participate in the study as evidenced by signing the informed consent document
• Female participants of childbearing potential must be 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:

• Pregnant 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 person's ability to understand and cooperate with the requirements of the study
• Screening laboratory values of Grade 1 or above for absolute neutrophil count (ANC), alanine aminotransferase (ALT), and serum creatinine, as defined in the protocol
• Any other condition that in the opinion of the investigator would jeopardize the safety or rights of a person participating in the study or would render the person unable to comply with the study
• Any significant alcohol or drug abuse in the 12 months before study entry which has caused medical, occupational, or family problems, as indicated by medical history
• History of a severe allergic reaction or anaphylaxis
• Severe asthma (emergency room visit or hospitalization in the 6 months before study entry)
• 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 42 days prior to or following vaccination; immunosuppressive dose of corticosteroids is defined as 10 mg or more of prednisone equivalent per day for 14 days or longer
• 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 42 days following vaccination

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• Johns Hopkins Bloomberg School of Public Health: collaborator

Study Sites (4)

Center for Immunization Research, Johns Hopkins School of Public Health

Washington D.C., District of Columbia, 20037, United States

Location

Center for Immunization Research, Johns Hopkins School of Public Health

Baltimore, Maryland, 21205, United States

Location

Fletcher Allen Health Care (FAHC), General Clinical Research Center (GCRC)

Burlington, Vermont, 05401, United States

Location

University of Vermont Vaccine Testing Center

Burlington, Vermont, 05401, United States

Location

Related Publications (7)

• Durbin AP, McArthur J, Marron JA, Blaney JE Jr, Thumar B, Wanionek K, Murphy BR, Whitehead SS. The live attenuated dengue serotype 1 vaccine rDEN1Delta30 is safe and highly immunogenic in healthy adult volunteers. Hum Vaccin. 2006 Jul-Aug;2(4):167-73. doi: 10.4161/hv.2.4.2944. Epub 2006 Jul 24.

  PMID: 17012875 BACKGROUND

• Blaney JE Jr, Durbin AP, Murphy BR, Whitehead SS. Targeted mutagenesis as a rational approach to dengue virus vaccine development. Curr Top Microbiol Immunol. 2010;338:145-58. doi: 10.1007/978-3-642-02215-9_11.

  PMID: 19802584 BACKGROUND

• Durbin AP, McArthur JH, Marron JA, Blaney JE, Thumar B, Wanionek K, Murphy BR, Whitehead SS. rDEN2/4Delta30(ME), a live attenuated chimeric dengue serotype 2 vaccine is safe and highly immunogenic in healthy dengue-naive adults. Hum Vaccin. 2006 Nov-Dec;2(6):255-60. doi: 10.4161/hv.2.6.3494. Epub 2006 Nov 5.

  PMID: 17106267 BACKGROUND

• Durbin AP, Whitehead SS, McArthur J, Perreault JR, Blaney JE Jr, Thumar B, Murphy BR, Karron RA. rDEN4delta30, a live attenuated dengue virus type 4 vaccine candidate, is safe, immunogenic, and highly infectious in healthy adult volunteers. J Infect Dis. 2005 Mar 1;191(5):710-8. doi: 10.1086/427780. Epub 2005 Jan 27.

  PMID: 15688284 BACKGROUND

• McArthur JH, Durbin AP, Marron JA, Wanionek KA, Thumar B, Pierro DJ, Schmidt AC, Blaney JE Jr, Murphy BR, Whitehead SS. Phase I clinical evaluation of rDEN4Delta30-200,201: a live attenuated dengue 4 vaccine candidate designed for decreased hepatotoxicity. Am J Trop Med Hyg. 2008 Nov;79(5):678-84.

  PMID: 18981503 BACKGROUND

• Kirkpatrick BD, Durbin AP, Pierce KK, Carmolli MP, Tibery CM, Grier PL, Hynes N, Diehl SA, Elwood D, Jarvis AP, Sabundayo BP, Lyon CE, Larsson CJ, Jo M, Lovchik JM, Luke CJ, Walsh MC, Fraser EA, Subbarao K, Whitehead SS. Robust and Balanced Immune Responses to All 4 Dengue Virus Serotypes Following Administration of a Single Dose of a Live Attenuated Tetravalent Dengue Vaccine to Healthy, Flavivirus-Naive Adults. J Infect Dis. 2015 Sep 1;212(5):702-10. doi: 10.1093/infdis/jiv082. Epub 2015 Mar 22.

  PMID: 25801652 DERIVED

• Durbin AP, Kirkpatrick BD, Pierce KK, Elwood D, Larsson CJ, Lindow JC, Tibery C, Sabundayo BP, Shaffer D, Talaat KR, Hynes NA, Wanionek K, Carmolli MP, Luke CJ, Murphy BR, Subbarao K, Whitehead SS. A single dose of any of four different live attenuated tetravalent dengue vaccines is safe and immunogenic in flavivirus-naive adults: a randomized, double-blind clinical trial. J Infect Dis. 2013 Mar 15;207(6):957-65. doi: 10.1093/infdis/jis936. Epub 2013 Jan 17.

  PMID: 23329850 DERIVED

MeSH Terms

Conditions

Dengue; Severe 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: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 19, 2010
• First Posted: February 22, 2010
• Study Start: July 1, 2010
• Primary Completion: June 1, 2012
• Study Completion: June 1, 2012
• Last Updated: January 3, 2013

Record last verified: 2012-12

Locations

US (4)