Safety and Immunogenicity Study to Assess TDV, a Live Attenuated Tetravalent Vaccine for Prevention of Dengue Fever

NCT ID: NCT01224639

Last Updated: 2018-06-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 96 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-10-11
• Study Completion Date: 2011-11-09

Brief Summary

The purpose of this study is to assess the safety of Takeda's Tetravalent Dengue Vaccine Candidate (TDV) (previously DENVax) in healthy adults when given as either a subcutaneous (SC) or intradermal (ID) injection at two dose levels (low and high). The vaccine will be given as two doses 90 days apart. Safety assessments include injection site evaluation and adverse events. The immune response generated after vaccination will be assessed up to 9 months after the first vaccination.

Detailed Description

This is a single center, placebo-controlled, randomized study assessing the safety and tolerability of two dose levels (low and high) of TDV administered subcutaneously or intradermally in two doses separated by an interval of 90 days. Initial dosing of low dose cohort will be performed and Day 21 safety assessed prior to administration of second dose to low dose cohort on Day 90 and initial dosing of high dose cohort. Day 21 safety for the high dose cohort will be assessed prior to administration of second dose for this cohort. Safety (local injection site reactions and solicited and unsolicited adverse events) will be assessed through Day 120 post-first (1 month after the second dose). Immunogenicity will be assessed at specified time points up to Day 120 post-prime (1 month after the second dose) and again on Days 180 and 270 (6 and 9 months post-first).

Conditions

Dengue Fever

Study Design

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

Study Groups

Group 1: Low Dose; SC

TDV-1: 8 x 10\^3 Plaque Forming Units (PFU), TDV-2: 5 x 10\^3 PFU, TDV-3: 1 x 10\^4 PFU, TDV-4: 2 x 10\^5 PFU or placebo administered subcutaneously on Days 0 and 90. Dose volume is 0.5 mL.

Group Type: EXPERIMENTAL

TDV - Low Dose

Intervention Type: BIOLOGICAL

TDV is a tetravalent dengue vaccine comprised of four recombinant, live attenuated dengue virus strains: TDV-1, TDV-2, TDV-3 and TDV-4. Low dose contains: TDV-1: 8 x 10\^3 PFU, TDV-2: 5 x 10\^3 PFU, TDV-3: 1 x 10\^4 PFU, and TDV-4: 2 x 10\^5 PFU, total virus per dose 2.2 x 10\^5 PFU

Group 2: Low Dose; ID

TDV-1: 8 x 10\^3 PFU, TDV-2: 5 x 10\^3 PFU, TDV-3: 1 x 10\^4 PFU, TDV-4: 2 x 10\^5 PFU or placebo administered intradermally on Days 0 and 90. Dose volume is 0.1 mL.

Group Type: EXPERIMENTAL

TDV - Low Dose

Intervention Type: BIOLOGICAL

TDV is a tetravalent dengue vaccine comprised of four recombinant, live attenuated dengue virus strains: TDV-1, TDV-2, TDV-3 and TDV-4. Low dose contains: TDV-1: 8 x 10\^3 PFU, TDV-2: 5 x 10\^3 PFU, TDV-3: 1 x 10\^4 PFU, and TDV-4: 2 x 10\^5 PFU, total virus per dose 2.2 x 10\^5 PFU

Group 3: High Dose; SC

TDV-1: 2 x 10\^4 PFU, TDV-2: 5 x 10\^4 PFU, TDV-3: 1 x 10\^5 PFU, TDV-4: 3 x 10\^5 PFU or placebo administered subcutaneously on Days 0 and 90. Dose volume is 0.5 mL.

Group Type: EXPERIMENTAL

TDV - High Dose

Intervention Type: BIOLOGICAL

TDV is a tetravalent dengue vaccine comprised of four recombinant, live attenuated dengue virus strains: TDV-1, TDV-2, TDV-3 and TDV-4. High dose contains TDV-1: 2 x 10\^4 PFU, TDV-2: 5 x 10\^4 PFU, TDV-3: 1 x 10\^5 PFU, and TDV-4: 3 x 10\^5 PFU, total virus per dose : 4.7 x 10\^5 PFU. TDV administered intradermally.

Group 4: High Dose; ID

TDV-1: 2 x 10\^4 PFU, TDV-2: 5 x 10\^4 PFU, TDV-3: 1 x 10\^5 PFU, TDV-4: 3 x 10\^5 PFU or placebo administered intradermally on Days 0 and 90. Dose volume is 0.1 mL.

Group Type: EXPERIMENTAL

TDV - High Dose

Intervention Type: BIOLOGICAL

TDV is a tetravalent dengue vaccine comprised of four recombinant, live attenuated dengue virus strains: TDV-1, TDV-2, TDV-3 and TDV-4. High dose contains TDV-1: 2 x 10\^4 PFU, TDV-2: 5 x 10\^4 PFU, TDV-3: 1 x 10\^5 PFU, and TDV-4: 3 x 10\^5 PFU, total virus per dose : 4.7 x 10\^5 PFU. TDV administered intradermally.

Placebo (SC)

Phosphate buffered saline administered subcutaneously in a volume of 0.5 mL.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: BIOLOGICAL

Phosphate Buffered Saline (PBS)

Placebo (ID)

Phosphate buffered saline administered intradermally in a dose volume of 0.1 mL.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: BIOLOGICAL

Phosphate Buffered Saline (PBS)

Interventions

TDV - Low Dose

TDV is a tetravalent dengue vaccine comprised of four recombinant, live attenuated dengue virus strains: TDV-1, TDV-2, TDV-3 and TDV-4. Low dose contains: TDV-1: 8 x 10\^3 PFU, TDV-2: 5 x 10\^3 PFU, TDV-3: 1 x 10\^4 PFU, and TDV-4: 2 x 10\^5 PFU, total virus per dose 2.2 x 10\^5 PFU

Intervention Type: BIOLOGICAL

TDV - High Dose

TDV is a tetravalent dengue vaccine comprised of four recombinant, live attenuated dengue virus strains: TDV-1, TDV-2, TDV-3 and TDV-4. High dose contains TDV-1: 2 x 10\^4 PFU, TDV-2: 5 x 10\^4 PFU, TDV-3: 1 x 10\^5 PFU, and TDV-4: 3 x 10\^5 PFU, total virus per dose : 4.7 x 10\^5 PFU. TDV administered intradermally.

Intervention Type: BIOLOGICAL

Placebo

Phosphate Buffered Saline (PBS)

Intervention Type: BIOLOGICAL

Other Intervention Names

Live attenuated tetravalent dengue vaccine; Live attenuated tetravalent dengue vaccine; PBS

Eligibility Criteria

Inclusion Criteria

• Is male or female aged 18 to 45 years, inclusive, at time of screening.
• Is in good health as determined by medical history, physical examination, and clinical safety laboratory examinations.
• Has body mass index (BMI) in the range 18-27 kilogram per square meter (kg/m^2).
• Has negative serology for Human Immunodeficiency Virus (HIV), Hepatitis C antibody, and Hepatitis B surface antigen.
• Females of child bearing potential must have a negative urine pregnancy test result during screening and a negative urine pregnancy test immediately prior to vaccination and be willing to use oral, implantable, transdermal or injectable contraceptives or another reliable means of contraception approved by the Investigator (intrauterine device, female condom, diaphragm with spermicidal, cervical cap, use of condom by the sexual partner or a sterile sexual partner, or abstinence) from screening until after the last blood sample (at Day 270).
• Is willing and able to give written informed consent to participate.
• Is willing and able to communicate with the Investigator and understand the requirements of the study.

Exclusion Criteria

• Has any condition which would limit the participant's ability to complete the study.
• Clinically significant hematological, renal, hepatic, pulmonary, central nervous system, cardiovascular or gastrointestinal disorders.
• Has abnormal electrocardiogram (ECG).
• Has febrile illness (temperature greater than or equal to (>=) 38 degree Celsius (°C) or 100.4 degree Fahrenheit (°F) or moderate or severe acute illness or infection within three days of vaccination.
• Diabetes mellitus.
• Has allergy to penicillin, neomycin, streptomycin or gentamicin.
• Hypersensitivity to any vaccine.
• Seropositivity to any of the four dengue serotypes (TDV-1, TDV-2, TDV-3 or TDV-4), yellow fever (YF) virus or West Nile (WN) virus.
• Has previous vaccination (in a clinical trial or with an approved product) against flaviviruses including dengue, YF or WN.
• Has planned vaccination against YF throughout the duration of this study.
• Has receipt of any vaccine in the 4 weeks preceding the first trial vaccination.
• Planned receipt of any vaccine in the 4 weeks following each of the vaccinations in this study.
• Travel to dengue-endemic areas in the two months prior to study start or planned travel to dengue-endemic areas during the study period, including low altitude regions of Colombia where dengue is endemic.
• Known or suspected congenital or acquired immunodeficiency, immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within the preceding 6 months prior to the first vaccination, or long- term (at least 2 weeks within the previous 3 months) systemic corticosteroids therapy (at a dose of at least 0.5 milligram per kilogram per day [mg/kg/day]) prior to the first vaccination.
• Has a history of recurring migraines or on prescription medication for treatment of recurring headaches or migraines.
• Use of any non-steroidal anti-inflammatory drugs (NSAIDs), acetaminophen or antihistamines for the 3 days immediately prior to each vaccination.
• Use of prescription or over the counter medications 7 days before the first vaccination (Day 0), excluding contraceptives and painkillers containing NSAIDs or acetaminophen, cold remedies, hormone replacement and antihistamines.
• Positive urine screen for cocaine, amphetamines, opiates, or cannabinoids.
• Receipt of any other investigational product or participation in any other clinical trial in the month before the first vaccination (Day 0) or during the conduct of this study.
• Receipt of blood products or immunoglobulins 8 weeks before the first vaccination (Day 0) or planned use during the study period.
• Donation of blood 6 weeks before the first vaccination (Day 0) or at any time during the study.
• Females who are pregnant or lactating.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Inviragen Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ivan D Velez, MD, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

PECET, Universidad the Antioquia, Medellin, Colombia

Locations

Program For The Study and Control of Tropical Diseases

Medellín, , Colombia

Countries

Colombia

References

Osorio JE, Velez ID, Thomson C, Lopez L, Jimenez A, Haller AA, Silengo S, Scott J, Boroughs KL, Stovall JL, Luy BE, Arguello J, Beatty ME, Santangelo J, Gordon GS, Huang CY, Stinchcomb DT. Safety and immunogenicity of a recombinant live attenuated tetravalent dengue vaccine (DENVax) in flavivirus-naive healthy adults in Colombia: a randomised, placebo-controlled, phase 1 study. Lancet Infect Dis. 2014 Sep;14(9):830-8. doi: 10.1016/S1473-3099(14)70811-4. Epub 2014 Jul 23.

Reference Type: DERIVED

PMID: 25087476 (View on PubMed)

Other Identifiers

U1111-1181-8290

Identifier Type: REGISTRY

Identifier Source: secondary_id

INV-DEN-102

Identifier Type: -

Identifier Source: org_study_id