Safety of and Immune Response of a 2-dose Regimen of rDEN1delta30 Dengue Virus Vaccine

NCT ID: NCT00473135

Last Updated: 2010-01-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-05-31

Brief Summary

Dengue fever, caused by dengue viruses, is a major health problem in tropical and subtropical regions of the world. The purpose of this study is to evaluate the safety of and immune response to a 2-dose regimen of a new monovalent dengue virus vaccine. This study will test the dengue virus vaccine DEN1delta30 in healthy adults.

Detailed Description

Dengue viruses account for more than 50 million cases of dengue fever and one half million cases annually of dengue hemorrhagic fever/shock syndrome. Dengue virus infections can cause illness ranging from mild, self-limited febrile illness to life threatening diseases. The goal of dengue vaccine development is to induce a long-lived antibody response against all four dengue serotypes. The rDEN1delta30 vaccine is a live attenuated dengue virus vaccine that may be protective against dengue serotype 1 (DEN1). The purpose of this study is to evaluate the safety, reactogenicity, and immunogenicity of a 2-dose regimen of rDEN1delta30 dengue virus vaccine. The regimen will differ in when the second booster shot of the vaccine is given.

This study will last 162 days (about 23 weeks) for those participants in Cohort 1, and 222 days (about 32 weeks) for those in Cohort 2. Participants in Cohort 1 will be randomly assigned to receive rDEN1delta30 vaccine or placebo on Study Day 0 and Study Day 120. Participants in Cohort 2 will be randomly assigned to receive rDEN1delta30 vaccine or placebo on Study Day 0 and Study Day 180.

There will be a total of 25 visits for each cohort. For both cohorts, the first and second vaccination days will include a physical exam and blood and urine collection, vital signs measurements, and receipt of the vaccine. A 30 minute observation period will follow vaccination. Participants will take their temperature at home three times a day for the first 16 days and report it in a diary. At all other study visits, vital signs measurements, a physical exam, and blood and/or urine collection will occur. At selected study visits, participants will turn in their diary cards.

Some participants may be asked to join an optional skin biopsy substudy.

Conditions

Dengue

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: TRIPLE

Study Groups

1

Two subcutaneous vaccinations with rDEN1delta30 into the deltoid region or either arm. One vaccination is given on Day 0 and one vaccination is given on Day 120.

Group Type: EXPERIMENTAL

rDEN1delta30

Intervention Type: BIOLOGICAL

Live attenuated rDEN1delta30 vaccine at a dose of 10\^3 PFU

2

Two subcutaneous vaccinations with rDEN1delta30 into the deltoid region or either arm. One vaccination is given on Day 0 and one vaccination is given on Day 180.

Group Type: EXPERIMENTAL

rDEN1delta30

Intervention Type: BIOLOGICAL

Live attenuated rDEN1delta30 vaccine at a dose of 10\^3 PFU

3

Two subcutaneous vaccinations with placebo into the deltoid region or either arm. One vaccination is given on Day 0 and one vaccination is given on either Day 120 or 180, depending on arm assignment.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: BIOLOGICAL

Placebo for rDEN1delta30

Interventions

rDEN1delta30

Live attenuated rDEN1delta30 vaccine at a dose of 10\^3 PFU

Intervention Type: BIOLOGICAL

Placebo

Placebo for rDEN1delta30

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• Good general health
• Available for the duration of the study (23 weeks for Cohort 1 and 32 weeks for Cohort 2)
• Willing to use acceptable forms of contraception for the duration of the study

Exclusion Criteria

• Clinically significant neurologic, heart, lung, liver, rheumatologic, autoimmune, or kidney disease
• Behavioral, cognitive, or psychiatric disease that, in the opinion of the investigator, may interfere with the study
• Significant laboratory abnormalities
• Medical, work, or family problems as a result of alcohol or illegal drug use within 12 months prior to study entry
• History of severe allergic reaction or anaphylaxis
• Severe asthma
• HIV-1 infected
• Hepatitis C virus (HCV) infected
• Hepatitis B surface antigen positive
• Known immunodeficiency syndrome
• Use of corticosteroids or immunosuppressive medications within 30 days prior to study entry. Individuals using topical or nasal corticosteroids are not excluded.
• Previous receipt of a live vaccine within 4 weeks prior to study entry
• Previous receipt of a killed vaccine within 2 weeks prior to study entry
• Absence of spleen
• Previous receipt of blood products within 6 months prior to study entry
• Previous receipt of dengue virus or other flavivirus (e.g., yellow fever virus, St.Louis encephalitis, West Nile virus) infection
• Previous receipt of yellow fever or dengue vaccine
• Plans to travel to an area where dengue infection is common
• Previous receipt of any investigational agent within 30 days prior to study entry
• Other condition that, in the opinion of the investigator, would affect participation in the study
• Pregnant or breastfeeding

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Johns Hopkins Bloomberg School of Public Health

OTHER

Sponsor Role: collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: lead

Responsible Party

Center for Immunization Research, Johns Hopkins School of Public Health

Principal Investigators

Anna Durbin, MD

Role: PRINCIPAL_INVESTIGATOR

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

Locations

Center for Immunization Research, Johns Hopkins School of Public Health

Baltimore, Maryland, United States

Countries

United States

References

Blaney JE Jr, Sathe NS, Hanson CT, Firestone CY, Murphy BR, Whitehead SS. Vaccine candidates for dengue virus type 1 (DEN1) generated by replacement of the structural genes of rDEN4 and rDEN4Delta30 with those of DEN1. Virol J. 2007 Feb 28;4:23. doi: 10.1186/1743-422X-4-23.

Reference Type: BACKGROUND

PMID: 17328799 (View on PubMed)

Chaturvedi UC, Shrivastava R, Nagar R. Dengue vaccines: problems and prospects. Indian J Med Res. 2005 May;121(5):639-52.

Reference Type: BACKGROUND

PMID: 15937367 (View on PubMed)

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.

Reference Type: BACKGROUND

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Reference Type: BACKGROUND

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Reference Type: BACKGROUND

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Rothman AL. Dengue: defining protective versus pathologic immunity. J Clin Invest. 2004 Apr;113(7):946-51. doi: 10.1172/JCI21512.

Reference Type: BACKGROUND

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Senanayake S. Dengue fever and dengue haemorrhagic fever--a diagnostic challenge. Aust Fam Physician. 2006 Aug;35(8):609-12.

Reference Type: BACKGROUND

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Katzelnick LC, Fonville JM, Gromowski GD, Bustos Arriaga J, Green A, James SL, Lau L, Montoya M, Wang C, VanBlargan LA, Russell CA, Thu HM, Pierson TC, Buchy P, Aaskov JG, Munoz-Jordan JL, Vasilakis N, Gibbons RV, Tesh RB, Osterhaus AD, Fouchier RA, Durbin A, Simmons CP, Holmes EC, Harris E, Whitehead SS, Smith DJ. Dengue viruses cluster antigenically but not as discrete serotypes. Science. 2015 Sep 18;349(6254):1338-43. doi: 10.1126/science.aac5017.

Reference Type: DERIVED

PMID: 26383952 (View on PubMed)

Other Identifiers

WIRB Protocol Number 20070718

Identifier Type: -

Identifier Source: secondary_id

CIR 229

Identifier Type: -

Identifier Source: org_study_id