Evaluating the Safety and Immune Response to Two Admixtures of a Tetravalent Dengue Virus Vaccine

Dengue Clinical Trial

Official title:

A Phase 1 Evaluation of the Safety and Immunogenicity of the Recombinant Live Attenuated Tetravalent Dengue Virus Vaccine Admixtures TV003 and TV005 in Healthy Flavivirus-experienced Adult Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01506570
• Other study ID #: CIR 280
• Status: Completed
• Phase: Phase 1
• First received: January 5, 2012
• Last updated: August 19, 2015
• Start date: December 2011
• Est. completion date: September 2013

Study information

• Verified date: August 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 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 to two formulations of a tetravalent dengue virus vaccine in healthy adults who have previously been infected with a dengue virus or other flavivirus or have previously received a flavivirus vaccine.

Description:

Dengue viruses cause dengue fever and the more severe condition, dengue hemorrhagic fever/shock syndrome. Dengue viruses are common in most tropical and subtropical regions of the world and infection with dengue viruses is the leading cause of hospitalization and death in children in many tropical Asian countries. For these reasons, the World Health Organization (WHO) has made the development of a dengue virus vaccine a top priority. This study will evaluate the safety and immunogenicity of two doses of a live attenuated, tetravalent dengue virus vaccine called TetraVax-DV in healthy adults (18-50 years old) who have previously been infected with a dengue virus or other flavivirus or have previously received a flavivirus vaccine. Two different formulations of the TetraVax-DV vaccine will be evaluated.

Participants will be randomly assigned to receive one of two admixtures of the TetraVax-DV vaccine or a placebo. At a baseline study visit (Day 0), participants will undergo a medical history review, physical examination, blood collection, vital sign measurements, and a pregnancy test for females. Participants will then receive one subcutaneous (SC) injection of their assigned vaccine or placebo in the upper arm. After receiving the vaccine, participants will remain in the clinic for 30 minutes for observation and monitoring. At home, participants will monitor and record their temperature three times a day for 16 days after the first vaccination (from Day 0 through Day 16) and for 16 days after the second vaccination (from Day 180 through Day 196). Additional study visits will occur at Days 3, 8, 10, 12, 14, 16, 21, 28, 56, 90, and 150 and will include a physical examination, vital sign measurements, and blood collection. On Day 180, participants will receive a second SC injection of their assigned vaccine or placebo. Additional study visits will then occur at Days 183, 188, 190, 192, 194, 196, 201, 208, 236, 270, and 360, and will include the same study procedures and monitoring that occurred after the first vaccination.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 58
• Est. completion date: September 2013
• Est. primary completion date: September 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 50 Years

Eligibility

Inclusion Criteria:

• In good general health, as determined by physical examination, laboratory screening, and review of medical history

• Documented history or serologic evidence of previous dengue virus infection or other flavivirus infection (e.g., yellow fever virus [YFV], St. Louis encephalitis virus [SLE], West Nile virus [WNV], Japanese encephalitis virus [JEV], or tick-borne encephalitis virus [TBEV]) or documented previous receipt of a flavivirus vaccine (licensed or experimental)

• Available for the duration of the study, approximately 26 weeks post-second 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.

Exclusion Criteria:

• Currently pregnant, as determined by positive beta-human choriogonadotropin (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

• 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 participant in the trial or would render the participant unable to comply with the protocol

• Any significant alcohol or drug abuse in the 12 months prior to study entry that has caused medical, occupational, or family problems, as indicated by a participant's history

• History of a severe allergic reaction or anaphylaxis

• Severe asthma (emergency room visit or hospitalization within the 6 months prior to 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 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 42 days following vaccination

• Asplenia

• Receipt of blood products within the 6 months prior to study entry, including transfusions or immunoglobulin or anticipated receipt of any blood products or immunoglobulin during the 42 days following vaccination

• Anticipated receipt of any investigational agent in the 42 days before or after vaccination

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

• Refusal to allow storage of specimens for future research

Additional Inclusion Criteria for Second Dose of Vaccine:

• In good general health, as determined by physical examination and review of medical history

• Available for the duration of the study, approximately 6 months post-vaccination

• 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.

Exclusion Criteria for Second Dose of Vaccine:

• Anaphylaxis or angioedema following the first dose of vaccine

• Currently pregnant, as determined by positive beta-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

• 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 12 months prior to study entry that has caused medical, occupational, or family problems, as indicated by a participant's history

• History of a severe allergic reaction or anaphylaxis

• Severe asthma (emergency room visit or hospitalization within the 6 months prior to study entry)

• 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 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 42 days following vaccination

• Asplenia

• Receipt of blood products within the 6 months prior to study entry, including transfusions or immunoglobulin or anticipated receipt of any blood products or immunoglobulin during the 42 days following vaccination

• Anticipated receipt of any other investigational agent in the 42 days before or after vaccination

• 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 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.

Ongoing Exclusion Criteria:

• Use of any investigational drug or investigational vaccine other than the study vaccine during the 42-day period post-vaccination

• Chronic administration (greater than or equal to 14 days) 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 42-day period post-vaccination (topical and nasal steroids are allowed)

• Receipt of a licensed vaccine during the 42-day period post-vaccination

• Receipt of immunoglobulins and/or any blood products during the 42-day period post-vaccination

• Pregnant

Study Design

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

Related Conditions & MeSH terms

• Dengue

Intervention

Biological:
• TetraVax-DV Vaccine - Admixture TV003
One SC injection at Day 0 and Day 180 of the TetraVax-DV Vaccine, Admixture TV003 (10^3 plaque-forming unit [PFU] of rDEN1?30, 10^3 PFU of rDEN2/4?30[ME], 10^3 PFU of rDEN3?30/31-7164, and 10^3 PFU of rDEN4?30)
• TetraVax-DV Vaccine - Admixture TV005
One SC injection at Day 0 and Day 180 of the TetraVax-DV Vaccine, Admixture TV005 (10^3 PFU of rDEN1?30, 10^4 PFU of rDEN2/4?30[ME], 10^3 PFU of rDEN3?30/31-7164, and 10^3 PFU of rDEN4?30)
• Placebo
One SC injection at Day 0 and Day 180 of placebo

Locations

Country	Name	City	State
United States	Center for Immunization Research, Johns Hopkins School of Public Health	Baltimore	Maryland
United States	Fletcher Allen Health Care (FAHC), General Clinical Research Center (GCRC)	Burlington	Vermont
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, 

References & Publications (3)

Bhamarapravati N, Sutee Y. Live attenuated tetravalent dengue vaccine. Vaccine. 2000 May 26;18 Suppl 2:44-7. — View Citation

Blaney JE Jr, Durbin AP, Murphy BR, Whitehead SS. Development of a live attenuated dengue virus vaccine using reverse genetics. Viral Immunol. 2006 Spring;19(1):10-32. Review. — View Citation

Durbin AP, Kirkpatrick BD, Pierce KK, Schmidt AC, Whitehead SS. Development and clinical evaluation of multiple investigational monovalent DENV vaccines to identify components for inclusion in a live attenuated tetravalent DENV vaccine. Vaccine. 2011 Sep 23;29(42):7242-50. doi: 10.1016/j.vaccine.2011.07.023. Epub 2011 Jul 21. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety of TetraVax-DV TV003 and TV005, as assessed by the frequency of vaccine-related adverse events		Measured through Day 360	Yes
Primary	Immunogenicity of TV003 and TV005, as assessed by neutralizing antibody titers to DENV-1, DENV-2, DENV-3, and DENV-4	Monovalent, bivalent, trivalent, and tetravalent seropositivity rates will be determined at 28, 56, and 90 days after each vaccination.	Measured 28, 56, 90, and 180 days after each vaccination	No
Primary	Whether a second dose of the vaccine given at Day 180 will induce seropositivity in those participants that remained seronegative to one or more DENV serotypes following the first vaccination		Measured through Day 360	No
Secondary	Frequency, quantity, and duration of viremia following vaccination		Measured through Day 360	No
Secondary	Number of flavivirus-experienced vaccinees infected with DENV-1, DENV-2, DENV-3, and DENV-4	Infection is defined as recovery of vaccine virus from the blood or serum of a participant and/or by developing seropositivity to DEN virus (plaque reduction neutralization titer [PRNT]50 greater than or equal to 1:10).	Measured through Day 360	No
Secondary	Duration of the neutralizing antibody response		Measured 26 weeks after each vaccination	No