long-term safety and antibody persistence of tdv and the impact of a booster dose

Conditions: Dengue Fever

Summary: the purpose of this study is to describe antibody persistence for each of the 4 dengue serotypes for up to 63 months after the first vaccination in the primary vaccination series for participants from parent trial den-315 (nct03341637) (mexico) and for up to 36 months after the first vaccination in the primary vaccination series for participants from parent trial den-304 (nct03423173) (united states \[us\]) and to describe the impact of a tetravalent dengue vaccine (tdv) booster dose vs placebo on antibody response for each of the 4 dengue serotypes at 1 month and 6 months post administration of the tdv booster or placebo.

the vaccine tested in this study is takeda's dengue tetravalent vaccine (live, attenuated) (tdv). this study will look at the long-term antibody persistence and safety of takeda's tdv in healthy adolescents and adults and will assess the impact of a booster dose. the study has enrolled 365 healthy participants. participants who previously received tdv in two parent trials (den-304 \[nct03423173\] and den-315 \[nct03341637\]), will be invited to participate in this follow-up trial. participants will be assessed for antibody persistence and safety from baseline (month 0) through month 15 (for participants from parent trial den-304 \[us\]) or month 42 (for participants from parent trial den-315 \[mexico\]). at month 15 (for participants from parent trial den-304 \[us\]) or at month 42 (for participants from parent trial den-315 \[mexico\]), eligible participants will be randomized in 1:1 ratio to one of two trial groups to receive tdv or placebo: a. group 1- tdv 0.5 ml subcutaneous (sc) injection at month 15 for participants from parent trial den-304 (us) or at month 42 for participants from parent trial den-315 (mexico\]). b. group 2- takeda's tetravalent dengue placebo (dummy sc injection - this is a liquid that looks like the study drug but has no active ingredient), 0.5 ml, subcutaneous injection at month 15 for participants from parent trial den-304 (us) or at month 42 for participants from parent trial den-315 (mexico). this multi-centre trial will be conducted in us and mexico. the overall time to participate in this study is up to 21 months for parent trial den-304 (us) and up to 48 months for parent trial den-315 (mexico). participants from parent trial den-304 (us) and participants from parent trial den-315 (mexico) will come for 5 visits to the clinic which includes a final visit (visit 5) 6 months after the booster dose for a follow-up assessment.

Eligibility criteria:
inclusion criteria: 1. male or female participants (irrespective of serostatus at baseline in the parent trials (den-304 \[(nct03423173)\] and den-315 \[nct03341637\]) who received at least one dose of takeda's tetravalent dengue vaccine candidate (tdv) in the parent trials and have data from at least one blood draw post-vaccination. exclusion criteria: 1. participants with a prolonged period of habitation (≥1 year) in a dengue endemic area within the 2 years prior to visit 1 day 1 (month 0). 2. previous and planned vaccination (during the trial conduct), against any flavivirus including dengue (other than takeda's tdv), yellow fever (yf), japanese encephalitis (je) viruses or tick-borne encephalitis. booster exclusion criteria: 1. participants for whom baseline serostatus is not defined in the parent trials (den-304 \[(nct03423173)\] and den-315 \[nct03341637\]). 2. participants with any history of progressive or severe neurologic disorder, seizure disorder or neuro-inflammatory disease (eg, guillain-barré syndrome). 3. known or suspected impairment/alteration of immune function, including: 1. chronic use of oral steroids (equivalent to 20 mg/day prednisone ≥12 weeks/≥2 mg/kg body weight/day prednisone ≥2 weeks) within 60 days prior to month 42 for participants from parent trial den-315 (mexico)/ month 15 for participants from parent trial den-304 (us); use of inhaled, intranasal, or topical corticosteroids is allowed. 2. receipt of parenteral steroids (equivalent to 20 mg/day prednisone ≥12 weeks/≥2 mg/kg body weight/day prednisone ≥2 weeks) within 60 days prior to month 42 for participants from parent trial den-315 (mexico)/ month 15 for participants from parent trial den-304 (us). 3. administration of immunoglobulins and/or any blood products within the 3 months prior to administration of the tdv booster or placebo at month 42 for participants from parent trial den-315 (mexico)/ month 15 for participants from parent trial den-304 (us); consider whether applicable as an exclusion criterion or criterion for delay. 4. receipt of immunostimulants within 60 days prior to month 42 for participants from parent trial den-315 (mexico)/ month 15 for participants from parent trial den-304 (us). 5. immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within 6 months prior to month 42 for participants from parent trial den-315 (mexico) / month 15 for participants from parent trial den-304 (us). 6. known human immunodeficiency virus (hiv) infection or hiv-related disease. 7. hepatitis c virus infection. 8. genetic immunodeficiency. 4. abnormalities of splenic or thymic function. 5. participants with a known bleeding diathesis, or any condition that may be associated with a prolonged bleeding time. 6. participants with history of current or previous infection with a flavivirus such as dengue, zika, yf, je, west nile fever, tick-borne encephalitis or murray valley encephalitis and participants with a prolonged period of habitation (≥1 year) in a dengue endemic area during trial conduct.

Keywords: vaccine