PMID- 35639602
OWN - NLM
STAT- MEDLINE
DCOM- 20230211
LR  - 20230220
IS  - 1537-6591 (Electronic)
IS  - 1058-4838 (Print)
IS  - 1058-4838 (Linking)
VI  - 76
IP  - 3
DP  - 2023 Feb 8
TI  - Clinical Safety Experience of TAK-003 for Dengue Fever: A New Tetravalent Live 
      Attenuated Vaccine Candidate.
PG  - e1350-e1359
LID - 10.1093/cid/ciac418 [doi]
AB  - BACKGROUND: An unmet medical need remains for an effective dengue tetravalent 
      vaccine that can be administered irrespective of previous dengue exposure. 
      TAK-003, a dengue tetravalent vaccine, has demonstrated efficacy in an ongoing 
      phase 3 trial in children and adolescents living in dengue-endemic areas, with an 
      acceptable safety profile in both dengue-naive and dengue-exposed individuals. 
      METHODS: Safety findings are presented herein from an integrated analysis of data 
      for healthy 4-60-year-olds from two phase 2 and three phase 3 double-blind, 
      placebo-controlled clinical trials of TAK-003 (TAK-003, n = 14 627; placebo, n = 
      7167). Safety evaluation included analyses of postinjection reactogenicity, 
      unsolicited adverse events (AEs), serious AEs (SAEs), and deaths. Subgroup 
      analyses were performed by age group, baseline serostatus, and gender. RESULTS: 
      The most common local and systemic AEs were injection site pain (43% for TAK-003 
      and 26% for placebo) and headache (34% and 30%, respectively). Injection site AEs 
      were mostly mild and resolved within 1-3 days. Unsolicited AEs and AEs leading to 
      discontinuation occurred with similar frequency across both groups, while SAEs 
      were fewer for TAK-003 recipients (6% vs 8% for placebo). Four of the 5 
      vaccine-related SAEs (which included hypersensitivity, dengue fever, and dengue 
      hemorrhagic fever) occurred in the placebo group. No deaths were considered 
      vaccine-related. Subgroup analyses showed no differences in safety by baseline 
      serostatus or by gender, albeit analysis by age indicated greater local 
      reactogenicity rates for adolescents (46% for TAK-003 and 28% for placebo) and 
      adults (56% and 19%, respectively) than for children (37% and 25%, respectively). 
      CONCLUSIONS: No important safety risks were identified, and TAK-003 was well 
      tolerated irrespective of age, gender, or baseline dengue serostatus in 
      recipients aged 4-60 years.
CI  - (c) The Author(s) 2022. Published by Oxford University Press on behalf of the 
      Infectious Diseases Society of America.
FAU - Patel, Sanjay S
AU  - Patel SS
AD  - Takeda Pharmaceuticals International AG, Zurich, Switzerland.
FAU - Rauscher, Martina
AU  - Rauscher M
AD  - Takeda Pharmaceuticals International AG, Zurich, Switzerland.
FAU - Kudela, Maria
AU  - Kudela M
AD  - Takeda Pharmaceuticals International Inc, Cambridge, Massachusetts, USA.
FAU - Pang, Hang
AU  - Pang H
AD  - Takeda Pharmaceuticals International Inc, Cambridge, Massachusetts, USA.
LA  - eng
PT  - Clinical Trial, Phase II
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Clin Infect Dis
JT  - Clinical infectious diseases : an official publication of the Infectious Diseases 
      Society of America
JID - 9203213
RN  - 0 (Antibodies, Viral)
RN  - 0 (Dengue Vaccines)
RN  - 0 (Vaccines, Attenuated)
SB  - IM
CIN - Clin Infect Dis. 2023 Jan 13;76(2):371-372. PMID: 36048521
MH  - Adolescent
MH  - Adult
MH  - Child
MH  - Child, Preschool
MH  - Humans
MH  - Middle Aged
MH  - Young Adult
MH  - Antibodies, Viral
MH  - *Dengue
MH  - *Dengue Vaccines
MH  - Double-Blind Method
MH  - Vaccines, Attenuated
PMC - PMC9907483
OTO - NOTNLM
OT  - TAK-003
OT  - adverse events
OT  - clinical safety
OT  - dengue tetravalent vaccine
OT  - hospitalization
COIS- Potential conflicts of interest . S. S. P., M. R., and H. P. are employees of 
      Takeda Pharmaceuticals. M. K. was an employee of Takeda Pharmaceuticals when the 
      integrated analysis was conducted. S. S. P., M. R., and H. P. also own stock in 
      Takeda Pharmaceuticals. H. P. reports royalties or licenses related to their PhD 
      in biostatistics; support from Takeda Pharmaceuticals for attending meetings 
      and/or travel; and stock or stock options from Takeda Pharmaceuticals. S. S. P. 
      and M.R. report support from Takeda Pharmaceuticals for attending meetings and/or 
      travel and stock/stock options from Takeda Pharmaceuticals. All authors have 
      submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. 
      Conflicts that the editors consider relevant to the content of the manuscript 
      have been disclosed.
EDAT- 2022/06/01 06:00
MHDA- 2023/02/11 06:00
PMCR- 2022/05/26
CRDT- 2022/05/31 16:05
PHST- 2022/01/18 00:00 [received]
PHST- 2022/06/01 06:00 [pubmed]
PHST- 2023/02/11 06:00 [medline]
PHST- 2022/05/31 16:05 [entrez]
PHST- 2022/05/26 00:00 [pmc-release]
AID - 6593313 [pii]
AID - ciac418 [pii]
AID - 10.1093/cid/ciac418 [doi]
PST - ppublish
SO  - Clin Infect Dis. 2023 Feb 8;76(3):e1350-e1359. doi: 10.1093/cid/ciac418.