Long-Term Safety and Antibody Persistence of TDV and the Impact of a Booster Dose

Dengue Fever Clinical Trial

Official title:

A Phase 3, Follow-Up Trial to Evaluate Long-Term Safety and Antibody Persistence, and the Impact of a Booster Dose of a Tetravalent Dengue Vaccine Candidate in Healthy Adolescents and Adults in Areas Non-Endemic for Dengue

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03999996
• Other study ID #: DEN-303
• Secondary ID: 2023-000027-36
• Status: Completed
• Phase: Phase 3
• Start date: November 12, 2019
• Est. completion date: May 25, 2024

Study information

• Verified date: May 2024
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 365
• Est. completion date: May 25, 2024
• Est. primary completion date: May 25, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 13 Years to 63 Years

Eligibility

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.

Related Conditions & MeSH terms

• Dengue
• Dengue Fever

Intervention

Biological:
• Takeda's Dengue Tetravalent Vaccine (Live, Attenuated) (TDV)
TDV subcutaneous injection
• Placebo
Normal Saline (0.9% NaCl) subcutaneous injection

Locations

Country	Name	City	State
Mexico	CAIMED Investigacion en Salud S.A de C.V.	Ciudad de Mexico
Mexico	Instituto Nacional de Pediatria	Ciudad De Mexico
United States	AES - DRS - Optimal Research Alabama - Huntsville	Huntsville	Alabama
United States	Alliance for Multispecialty Research, LLC - Newton - PPDS	Newton	Kansas
United States	AES - DRS - Synexus Clinical Research US, Inc. - Omaha	Papillion	Nebraska
United States	AES - DRS - Optimal Research Illinois - Peoria	Peoria	Illinois
United States	AES - DRS - Synexus Clinical Research US, Inc. Minneapolis	Richfield	Minnesota
United States	Optima Research	Rockville	Maryland
United States	AES - DRS - Synexus Clinical Research US, Inc. - St. Louis	Saint Louis	Missouri
United States	Advanced Clinical Research/Velocity Clinical Research	West Jordan	Utah

Sponsors (1)

Lead Sponsor	Collaborator
Takeda

Countries where clinical trial is conducted

United States,  Mexico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Geometric Mean Titers (GMTs) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes Prior to the Booster Dose at Month 0 (Day 1)	GMTs of neutralizing antibodies will be measured by microneutralization test 50% [MNT50] for each of the 4 Dengue Serotypes for all participants, for all participants by parent trial (DEN-304 and DEN-315), and for all participants by serostatus at baseline in the parent trials (DEN-304 and DEN-315). The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4.	Month 0 (Day 1)
Primary	Geometric Mean Titers (GMTs) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes Prior to the Booster Dose at Month 12	GMTs of neutralizing antibodies will be measured by microneutralization test 50% [MNT50] for each of the 4 Dengue Serotypes for all participants, for all participants by parent trial (DEN-304 and DEN-315), and for all participants by serostatus at baseline in the parent trials (DEN-304 and DEN-315). The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4.	Month 12
Primary	Geometric Mean Titers (GMTs) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes Prior to the Booster Dose at Month 15 (US)	GMTs of neutralizing antibodies will be measured by microneutralization test 50% [MNT50] for each of the 4 Dengue Serotypes for all participants, for all participants by parent trial (DEN-304 and DEN-315), and for all participants by serostatus at baseline in the parent trials (DEN-304 and DEN-315). The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4.	Month 15 (US)
Primary	Geometric Mean Titers (GMTs) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes Prior to the Booster Dose at Month 42 (Mexico)	GMTs of neutralizing antibodies will be measured by microneutralization test 50% [MNT50] for each of the 4 Dengue Serotypes for all participants, for all participants by parent trial (DEN-304 and DEN-315), and for all participants by serostatus at baseline in the parent trials (DEN-304 and DEN-315). The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4.	Month 42 (Mexico)
Primary	Percentage of Participants Seropositive for Each of the 4 Dengue Serotypes Prior to the Booster Dose at Month 0 (Day 1)	Seropositivity rate, defined as the percentage of participants seropositive, is derived from the titers of dengue-neutralizing antibodies. Seropositivity is defined as a reciprocal neutralizing titer =10. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Seropositivity rate will be calculated for all participants, for all participants by parent trial (DEN-304 and DEN-315), and for all participants by serostatus at baseline in the parent trials (DEN-304 and DEN-315).	Month 0 (Day 1)
Primary	Percentage of Participants Seropositive for Each of the 4 Dengue Serotypes Prior to the Booster Dose at Month 12	Seropositivity rate, defined as the percentage of participants seropositive, is derived from the titers of dengue-neutralizing antibodies. Seropositivity is defined as a reciprocal neutralizing titer =10. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Seropositivity rate will be calculated for all participants, for all participants by parent trial (DEN-304 and DEN-315), and for all participants by serostatus at baseline in the parent trials (DEN-304 and DEN-315).	Month 12
Primary	Percentage of Participants Seropositive for Each of the 4 Dengue Serotypes Prior to the Booster Dose at Month 15 (US)	Seropositivity rate, defined as the percentage of participants seropositive, is derived from the titers of dengue-neutralizing antibodies. Seropositivity is defined as a reciprocal neutralizing titer =10. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Seropositivity rate will be calculated for all participants, for all participants by parent trial (DEN-304 and DEN-315), and for all participants by serostatus at baseline in the parent trials (DEN-304 and DEN-315).	Month 15 (US)
Primary	Percentage of Participants Seropositive for Each of the 4 Dengue Serotypes Prior to the Booster Dose at Month 42 (Mexico)	Seropositivity rate, defined as the percentage of participants seropositive, is derived from the titers of dengue-neutralizing antibodies. Seropositivity is defined as a reciprocal neutralizing titer =10. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Seropositivity rate will be calculated for all participants, for all participants by parent trial (DEN-304 and DEN-315), and for all participants by serostatus at baseline in the parent trials (DEN-304 and DEN-315).	Month 42 (Mexico)
Primary	Percentage of Participants Seropositive for Multiple (2, 3 or 4) Dengue Serotypes Prior to the Booster Dose at Month 0 (Day 1)	Seropositivity rate for multiple Dengue serotypes, defined as the percentage of participants seropositive for more than one Dengue serotype, is derived from the titers of dengue-neutralizing antibodies. Seropositivity is defined as a reciprocal neutralizing titer =10. Seropositivity rate will be calculated for all participants, for all participants by parent trial (DEN-304 and DEN-315), and for all participants by serostatus at baseline in the parent trials (DEN-304 and DEN-315).	Month 0 (Day 1)
Primary	Percentage of Participants Seropositive for Multiple (2, 3 or 4) Dengue Serotypes Prior to the Booster Dose at Month 12	Seropositivity rate for multiple Dengue serotypes, defined as the percentage of participants seropositive for more than one Dengue serotype, is derived from the titers of dengue-neutralizing antibodies. Seropositivity is defined as a reciprocal neutralizing titer =10. Seropositivity rate will be calculated for all participants, for all participants by parent trial (DEN-304 and DEN-315), and for all participants by serostatus at baseline in the parent trials (DEN-304 and DEN-315).	Month 12
Primary	Percentage of Participants Seropositive for Multiple (2, 3 or 4) Dengue Serotypes Prior to the Booster Dose Month 15 (US)	Seropositivity rate for multiple Dengue serotypes, defined as the percentage of participants seropositive for more than one Dengue serotype, is derived from the titers of dengue-neutralizing antibodies. Seropositivity is defined as a reciprocal neutralizing titer =10. Seropositivity rate will be calculated for all participants, for all participants by parent trial (DEN-304 and DEN-315), and for all participants by serostatus at baseline in the parent trials (DEN-304 and DEN-315).	Month 15 (US)
Primary	Percentage of Participants Seropositive for Multiple (2, 3 or 4) Dengue Serotypes Prior to the Booster Dose at Month 42 (Mexico)	Seropositivity rate for multiple Dengue serotypes, defined as the percentage of participants seropositive for more than one Dengue serotype, is derived from the titers of dengue-neutralizing antibodies. Seropositivity is defined as a reciprocal neutralizing titer =10. Seropositivity rate will be calculated for all participants, for all participants by parent trial (DEN-304 and DEN-315), and for all participants by serostatus at baseline in the parent trials (DEN-304 and DEN-315).	Month 42 (Mexico)
Primary	GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at 1 Month Post-Booster Dose at Month 16 (US)	GMTs of neutralizing antibodies will be measured by MNT50 for each of the 4 Dengue Serotypes for participants from parent trial DEN-304 (US) and DEN-315 (Mexico) randomized to Groups 1 and 2 by current trial group, and by current trial group and serostatus at baseline in the parent trial DEN-304 (US) and DEN-315 (Mexico). The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4.	1 month post-booster dose at Month 16 (US)
Primary	GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at 1 Month Post-Booster Dose at Month 43 (Mexico)	GMTs of neutralizing antibodies will be measured by MNT50 for each of the 4 Dengue Serotypes for participants from parent trial DEN-304 (US) and DEN-315 (Mexico) randomized to Groups 1 and 2 by current trial group, and by current trial group and serostatus at baseline in the parent trial DEN-304 (US) and DEN-315 (Mexico). The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4.	1 month post-booster dose at Month 43 (Mexico)
Primary	GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at 6 Months Post-Booster Dose at Month 21 (US)	GMTs of neutralizing antibodies will be measured by MNT50 for each of the 4 Dengue Serotypes for participants from parent trial DEN-304 (US) and DEN-315 (Mexico) randomized to Groups 1 and 2 by current trial group, and by current trial group and serostatus at baseline in the parent trial DEN-304 (US) and DEN-315 (Mexico). The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4.	6 months post-booster dose at Month 21 (US)
Primary	GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at 6 Months Post-Booster Dose at Month 48 (Mexico)	GMTs of neutralizing antibodies will be measured by MNT50 for each of the 4 Dengue Serotypes for participants from parent trial DEN-304 (US) and DEN-315 (Mexico) randomized to Groups 1 and 2 by current trial group, and by current trial group and serostatus at baseline in the parent trial DEN-304 (US) and DEN-315 (Mexico). The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4.	6 months post-booster dose at Month 48 (Mexico)
Primary	Percentage of Participants Seropositive for Each of the 4 Dengue Serotypes at 1 Month Post-Booster Dose at Month 16 (US)	Seropositivity rate, defined as the percentage of participants seropositive, is derived from the titers of dengue-neutralizing antibodies. Seropositivity is defined as a reciprocal neutralizing titer =10. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Seropositivity rate will be calculated for participants from parent trials DEN-304 (US) and DEN-315 (Mexico) randomized to Groups 1 and 2 by current trial group, and by current trial group and serostatus at baseline in the parent trials DEN-304 (US) and DEN-315 (Mexico).	1 month post-booster dose at Month 16 (US)
Primary	Percentage of Participants Seropositive for Each of the 4 Dengue Serotypes at 1 Month Post-Booster Dose at Month 43 (Mexico)	Seropositivity rate, defined as the percentage of participants seropositive, is derived from the titers of dengue-neutralizing antibodies. Seropositivity is defined as a reciprocal neutralizing titer =10. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Seropositivity rate will be calculated for participants from parent trials DEN-304 (US) and DEN-315 (Mexico) randomized to Groups 1 and 2 by current trial group, and by current trial group and serostatus at baseline in the parent trials DEN-304 (US) and DEN-315 (Mexico).	1 month post-booster dose at Month 43 (Mexico)
Primary	Percentage of Participants Seropositive for Each of the 4 Dengue Serotypes at 6 Months Post-Booster Dose at Month 21 (US)	Seropositivity rate, defined as the percentage of participants seropositive, is derived from the titers of dengue-neutralizing antibodies. Seropositivity is defined as a reciprocal neutralizing titer =10. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Seropositivity rate will be calculated for participants from parent trials DEN-304 (US) and DEN-315 (Mexico) randomized to Groups 1 and 2 by current trial group, and by current trial group and serostatus at baseline in the parent trials DEN-304 (US) and DEN-315 (Mexico).	6 months post-booster dose at Month 21 (US)
Primary	Percentage of Participants Seropositive for Each of the 4 Dengue Serotypes at 6 Months Post-Booster Dose at Month 48 (Mexico)	Seropositivity rate, defined as the percentage of participants seropositive, is derived from the titers of dengue-neutralizing antibodies. Seropositivity is defined as a reciprocal neutralizing titer =10. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Seropositivity rate will be calculated for participants from parent trials DEN-304 (US) and DEN-315 (Mexico) randomized to Groups 1 and 2 by current trial group, and by current trial group and serostatus at baseline in the parent trials DEN-304 (US) and DEN-315 (Mexico).	6 months post-booster dose at Month 48 (Mexico)
Primary	Percentage of Participants Seropositive for Multiple (2, 3 or 4) Dengue Serotypes at 1 Month Post-Booster Dose at Month 16 (US)	Seropositivity rate for multiple Dengue serotypes, defined as the percentage of participants seropositive for more than one Dengue serotype, is derived from the titers of dengue-neutralizing antibodies. Seropositivity is defined as a reciprocal neutralizing titer =10. Seropositivity rate will be calculated for participants from parent trial DEN-304 (US) and DEN-315 (Mexico) randomized to Groups 1 and 2 by current trial group, and by current trial group and serostatus at baseline in the parent trial DEN-304 (US) and DEN-315 (Mexico).	1 month post-booster dose at Month 16 (US)
Primary	Percentage of Participants Seropositive for Multiple (2, 3 or 4) Dengue Serotypes Post-Booster Dose at 1 Month Post-Booster Dose at Month 43 (Mexico)	Seropositivity rate for multiple Dengue serotypes, defined as the percentage of participants seropositive for more than one Dengue serotype, is derived from the titers of dengue-neutralizing antibodies. Seropositivity is defined as a reciprocal neutralizing titer =10. Seropositivity rate will be calculated for participants from parent trial DEN-304 (US) and DEN-315 (Mexico) randomized to Groups 1 and 2 by current trial group, and by current trial group and serostatus at baseline in the parent trial DEN-304 (US) and DEN-315 (Mexico).	1 month post-booster dose at Month 43 (Mexico)
Primary	Percentage of Participants Seropositive for Multiple (2, 3 or 4) Dengue Serotypes Post-Booster Dose at 6 Months Post-Booster Dose at Month 21 (US)	Seropositivity rate for multiple Dengue serotypes, defined as the percentage of participants seropositive for more than one Dengue serotype, is derived from the titers of dengue-neutralizing antibodies. Seropositivity is defined as a reciprocal neutralizing titer =10. Seropositivity rate will be calculated for participants from parent trial DEN-304 (US) and DEN-315 (Mexico) randomized to Groups 1 and 2 by current trial group, and by current trial group and serostatus at baseline in the parent trial DEN-304 (US) and DEN-315 (Mexico).	6 months post-booster dose at Month 21 (US)
Primary	Percentage of Participants Seropositive for Multiple (2, 3 or 4) Dengue Serotypes Post-booster Dose at 6 Months Post-Booster Dose at Month 48 (Mexico)	Seropositivity rate for multiple Dengue serotypes, defined as the percentage of participants seropositive for more than one Dengue serotype, is derived from the titers of dengue-neutralizing antibodies. Seropositivity is defined as a reciprocal neutralizing titer =10. Seropositivity rate will be calculated for participants from parent trial DEN-304 (US) and DEN-315 (Mexico) randomized to Groups 1 and 2 by current trial group, and by current trial group and serostatus at baseline in the parent trial DEN-304 (US) and DEN-315 (Mexico).	6 months post-Booster dose at Month 48 (Mexico)
Secondary	Geometric Mean Ratio (GMR) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes for all Participants Prior to the Booster Dose	GMR of neutralizing antibodies will be calculated for all participants, for all participants by parent trial (DEN-304 and DEN-315), and for all participants by serostatus at baseline in the parent trial (DEN-304 and DEN-315).	Month 0 vs Month 12 in the current trial, Month 4 in the parent trials vs Month 15 (US) and Month 42 (Mexico) in the current trials, Month 9 in the parent trials vs Month 0 and Month 12 in the current trial
Secondary	GMR of Neutralizing Antibodies for Each of the 4 Dengue Serotypes Post-booster Dose	GMR of neutralizing antibodies will be calculated for participants randomized to Groups 1 and 2 by current trial group, by current trial group and parent trial (DEN-304 and DEN-315), and by trial group and serostatus at baseline in the parent trial (DEN-304 and DEN-315).	Month 4 in the parent trials vs 1 and 6 months post-booster dose in the current trial; Month 15 (US)/Month 42 (Mexico) vs 1 month post-booster dose; Month 15 (US)/Month 42 (Mexico) vs 6 month post-booster dose; 1 vs 6 month post-booster dose
Secondary	Percentage of Participants with Solicited Local Injection Site Adverse Events (AEs) by Severity, Post-booster Dose	Solicited local AEs at injection site are defined as pain, erythema and swelling that occurred within 7 days post-booster dose at Month 15 (US) and Month 42 (Mexico).	Days 1 through 7 post-booster dose at Month 15 (US) and Month 42 (Mexico)
Secondary	Percentage of Participants with Solicited Systemic AEs by Severity Post-booster Dose	Solicited systemic AEs are defined as fever, headache, asthenia, malaise and myalgia that occurred within 14 days post-booster dose at Month 15 (US) and Month 42 (Mexico).	Days 1 through 14 post-booster dose at Month 15 (US) and Month 42 (Mexico)
Secondary	Percentage of Participants with any Unsolicited AEs Post-booster Dose	An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a trial vaccine or placebo; it does not necessarily have to have a causal relationship with this treatment.	Days 1 through 28 post-booster dose at Month 15 (US) and Month 42 (Mexico)
Secondary	Percentage of Participants with any Medically Attended AEs (MAAEs) Post-booster Dose	MAAEs are defined as AEs leading to an unscheduled visit to or by a healthcare professional including visits to an emergency department, but not fulfilling seriousness criteria.	Month 15 post-booster dose through Month 21 (US); Month 42 post-booster dose through Month 48 (Mexico)
Secondary	Percentage of Participants with any Serious Adverse Events (SAEs) Prior to the Booster Dose	A SAE is defined as any untoward medical occurrence or effect that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically important due to other reasons than the above mentioned criteria.	Month 0 through Month 15 (US) and Month 42 (Mexico)
Secondary	Percentage of Participants with any SAEs Post-Booster Dose	A SAE is defined as any untoward medical occurrence or effect that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically important due to other reasons than the above mentioned criteria.	Month 15 post-booster dose after vaccination through Month 21 (US); Month 42 post-booster dose after vaccination through Month 48 (Mexico)

External Links

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