Evaluating the Safety and Effectiveness of a Dengue Virus Vaccine in Healthy Adults

Dengue Clinical Trial

Official title:

A Phase 1 Evaluation of the Protective Efficacy of a Single Dose of the Live Attenuated Tetravalent Dengue Vaccine TV003 to Protect Against Infection With Attenuated DENV-2, rDEN2∆30-7169

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02021968
• Other study ID #: CIR 287
• Status: Completed
• Phase: Phase 1
• First received: December 20, 2013
• Last updated: December 14, 2015
• Start date: November 2013
• Est. completion date: December 2015

Study information

• Verified date: December 2015
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

Dengue viruses can cause dengue illness ranging from a mild illness to life-threatening disease. The purpose of this study is to evaluate the protective effectiveness of a dengue virus vaccine in healthy adults.

Description:

There are 4 types of dengue virus (DENV-1, DENV-2, DENV-3, and DENV-4); each can cause dengue illness ranging from a mild illness to life-threatening disease. More than 2 billion persons in tropical and subtropical regions of the world are at risk for acquiring dengue, which is why development of a dengue vaccine is a top public health priority.

The purpose of this study is to evaluate the ability of a single dose of TetraVax-DV-TV003 (TV003) vaccine to protect against infection with rDEN2∆30, an attenuated candidate DENV-2 vaccine.

This study will enroll healthy adults with no history of previous infection with a flavivirus (any of a group of viruses that includes the dengue virus). Participants will be randomly assigned to receive either the TV003 vaccine or placebo vaccine on Day 0 (study entry). At Day 180, all participants will receive an injection of the "challenge" virus, rDEN2∆30, an attenuated (weakened) DENV-2 vaccine. For at least 30 minutes after each vaccination, participants will remain in the study clinic to be monitored for any adverse effects of the vaccines. Participants will record their temperature at least 3 times a day for 16 days after the first and second vaccinations.

In addition to vaccination visits at Day 0 and Day 180, participants will attend study visits at Day 2, 4, 6, 8, 10, 12, 14, 16, 21, 28, 56, 90, 150, 182, 184, 186, 188, 190, 192, 194, 196, 201, 208, 236, 270, and 360. At all study visits, participants will give a medical history and undergo a blood collection; at most study visits, participants will undergo a physical examination. Female participants will have a pregnancy test at select study visits.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 48
• Est. completion date: December 2015
• Est. primary completion date: March 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 50 Years

Eligibility

Inclusion Criteria:

• 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 after second inoculation

• Willingness to participate in the study as evidenced by signing the informed consent document

• Females Only: Female participants of childbearing potential willing to use effective contraception. Reliable methods of contraception include: hormonal birth control, condoms with spermicide, diaphragm with spermicide, surgical sterilization, intrauterine device, and abstinence (6 months or more since last sexual encounter). All female participants will be considered having child-bearing potential except for those with hysterectomy, tubal ligation, tubal coil (at least 3 months prior to vaccination), or post-menopausal status documented as at least 1 year since last menstrual period.

Exclusion Criteria:

• Females Only: Currently pregnant, as determined by positive beta-human choriogonadotropin (HCG) test, breast-feeding

• 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

• Screening laboratory values of Grade 1 or above for absolute neutrophil count (ANC), alanine aminotransferase (ALT), and serum creatinine as defined in the study protocol.

• Any other condition that in the opinion of the investigator would jeopardize the safety or rights of a participant participating 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 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 28 days following vaccination

• Asplenia

• Receipt of blood products within the past 6 months, including transfusions or immunoglobulin or anticipated receipt of any blood products or immunoglobulin during the 28 days following vaccination

• History or serologic evidence of previous dengue virus infection or other flavivirus infection (e.g., yellow fever virus, St. Louis encephalitis virus, West Nile virus)

• Previous receipt of a flavivirus vaccine (licensed or experimental)

• Anticipated receipt of any investigational agent in the 28 days before or after vaccination

• Participant has definite plans to travel to a dengue endemic area during the study

• Refusal to allow storage of specimens for future research

Inclusion Criteria for Second Vaccine

• Good general health as determined by physical examination and review of medical history

• Available for the duration of the study, approximately 26 weeks after the second dose

• Willingness to participate in the study as evidenced by signing the informed consent document

• Females Only: Female participants of childbearing potential willing to use effective contraception for the duration of the trial. Reliable methods of contraception include: hormonal birth control, condoms with spermicide, diaphragm with spermicide, surgical sterilization, intrauterine device, and abstinence (6 months or more since last sexual encounter). All female participants will be considered having child-bearing potential except for those with hysterectomy, tubal ligation, tubal coil (at least 3 months prior to vaccination), or post-menopausal status documented as at least 1 year since last menstrual period.

Exclusion Criteria for Second Vaccine

• Anaphylaxis or angioedema following the first dose of vaccine

• Females Only: Currently pregnant, as determined by positive beta-HCG test, breast-feeding

• 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

• Any other condition that in the opinion of the investigator would jeopardize the safety or rights of a participant participating 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

• HCV infection, by screening and confirmatory assays

• HBV infection, by 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 greater than or equal to 10 mg 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 28 days following vaccination

• Asplenia

• Receipt of blood products within the past 6 months, including transfusions or immunoglobulin or anticipated receipt of any blood products or immunoglobulin during the 28 days following vaccination

• Anticipated receipt of any other investigational agent in the 28 days before or after vaccination

• Participant has definite plans to travel to a dengue endemic area during the study

• Refusal to allow storage of specimens for future research

Other Treatments and Ongoing Exclusion Criteria

The following criteria will be reviewed on Study Days 28 and 56 following each vaccination. If any become applicable during the study, the participant will not be included in further immunogenicity evaluations, as of the exclusionary visit. The participant will, however, be encouraged to remain in the study for safety evaluations for the duration of the study.

• Use of any investigational drug or investigational vaccine other than the study vaccine during the 28-day period after vaccination

• Chronic administration (14 days or longer) of steroids (defined as prednisone equivalent of greater than or equal to 10 mg per day), immunosuppressants, or other immune-modifying drugs initiated during the 28-day period after vaccination (topical and nasal steroids are allowed)

• Receipt of a licensed vaccine during the 28-day period after vaccination

• Receipt of immunoglobulins and/or any blood products during the 28-day period after vaccination

• Pregnancy

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Dengue

Intervention

Biological:
• TetraVax-DV-TV003
TetraVax-DV-TV003 is a live attenuated recombinant tetravalent dengue virus vaccine, which will be administered as a 0.5 mL dose containing 10^3.0 plaque forming units (PFUs) each of DENV-1, DENV-2, DENV-3, and DENV-4. It will be delivered by subcutaneous injection in the deltoid region of the upper arm.
• rDEN2?30-7169
The challenge virus, rDEN2?30-7169, is a live recombinant attenuated DENV-2 candidate vaccine virus and will be administered as a 0.5 mL dose containing 10^3 PFUs of rDEN2?30-7169. It will be delivered by subcutaneous injection in the deltoid region of the upper arm.
• Placebo
The placebo vaccine is the vaccine diluent 1X L-15, which will be administered as a 0.5 mL dose delivered by subcutaneous injection in the deltoid region of the upper arm.

Locations

Country	Name	City	State
United States	Center for Immunization Research (CIR), Johns Hopkins Bloomberg School of Public Health	Baltimore	Maryland
United States	University of Vermont Vaccine Testing Center	Burlington	Vermont

Sponsors (1)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Frequency of viremia following TV003 vaccination		Measured through Day 16 visit	Yes
Other	Quantity of viremia following TV003 vaccination		Measured through Day 16 visit	Yes
Other	Duration of viremia following TV003 vaccination		Measured through Day 16 visit	Yes
Other	Determine if peak neutralizing antibody (NAb) titer against DENV-2 following TV003 vaccination or NAb titer against DENV-2 measured at Day 180 correlates with protection against viremia, rash, and/or neutropenia following inoculation with rDEN2?30-7169	Neutralizing antibodies will be measured through Day 180 following vaccination with TV003; viremia, rash, and neutropenia elicited by DEN2?30-7169 will be measured from Day 180 through Day 208	Measured through Day 208	Yes
Primary	Protection against viremia induced by rDEN2?30, determined by rDEN2?20-7169 titer	Participants will receive rDEN2?30-7169 at Day 180. Viremia caused by rDEN2?30-7160 will be measured through Day 196. Blood samples will be obtained from all participants on Days 180, 182, 184, 186, 188, 190, 192, 194, and 196, and the titer of rDEN2?20-7169 will be determined.	Measured through Day 196	Yes
Primary	Frequency of TV003 and rDEN2?30-7169-related adverse events (AEs), as classified by both severity and seriousness, through active and passive surveillance		Measured through participants' last study visit on Day 360	Yes
Primary	Dengue virus neutralizing antibody titer	Seropositivity to each serotype will be defined as a PRNT50 of greater than or equal to 1:10 by Day 90 (TV003) and by Day 270 (rDEN2?30-7169).	Measured through participants' last study visit on Day 360	No