PMID- 37884415
OWN - NLM
STAT- MEDLINE
DCOM- 20231103
LR  - 20231103
IS  - 1873-2518 (Electronic)
IS  - 0264-410X (Linking)
VI  - 41
IP  - 47
DP  - 2023 Nov 13
TI  - Consistency of immunogenicity in three consecutive lots of a tetravalent dengue 
      vaccine candidate (TAK-003): A randomized placebo-controlled trial in US adults.
PG  - 6999-7006
LID - S0264-410X(23)01132-5 [pii]
LID - 10.1016/j.vaccine.2023.09.049 [doi]
AB  - BACKGROUND: We conducted a trial to demonstrate immunogenic equivalence of three 
      consecutive manufacturing lots of Takeda's tetravalent dengue vaccine candidate, 
      TAK-003, and further assessed its safety and reactogenicity. METHODS: Healthy US 
      adults (n = 923) randomized 2:2:2:1 to four groups received two doses of one of 
      three TAK-003 lots or placebo on Days 0 and 90, with follow-up to Day 270. 
      Primary endpoint evaluated lot-to-lot equivalence of geometric mean neutralizing 
      titers at Day 120 against each of 4 dengue serotypes in baseline seronegative 
      participants. Solicited local and systemic, and unsolicited adverse events (AEs) 
      were assessed for 7, 14 and 28 days after each dose, respectively. Serious AEs 
      (SAE) were monitored throughout the study. RESULTS: Eight of 12 prespecified 
      equivalence comparisons were met in the per-protocol set but failed marginally in 
      the other 4 mainly due to loss of statistical power following higher than 
      anticipated baseline seropositivity and drop-out rates. All three TAK-003 lots 
      elicited high rates of tetravalent dengue seropositivity (96.7 %, 93.0 % and 
      97.5 % at Day 120; 91.0 %, 80.5 % and 85.7 % at Day 270) and had similar 
      reactogenicity profiles with no vaccine-related SAEs. CONCLUSIONS: The three lots 
      of TAK-003 were immunogenic for all four dengue serotypes and well tolerated in 
      healthy adults. Despite not meeting all equivalence comparisons, no major 
      differences were observed between lots and the data support acceptable 
      consistency of the manufacturing process. Trial registrationClinicalTrials.gov 
      identifier: NCT03423173.
CI  - Copyright (c) 2023 Takeda Vaccines. Published by Elsevier Ltd.. All rights 
      reserved.
FAU - Tricou, Vianney
AU  - Tricou V
AD  - Takeda Pharmaceuticals International, Zurich, Switzerland. Electronic address: 
      vianney.tricou@takeda.com.
FAU - Winkle, Peter J
AU  - Winkle PJ
AD  - Anaheim Clinical Trials, Anaheim, CA, USA.
FAU - Tharenos, Leslie M
AU  - Tharenos LM
AD  - Synexus - St. Louis, St. Louis, MO, USA.
FAU - Rauscher, Martina
AU  - Rauscher M
AD  - Takeda Pharmaceuticals International, Zurich, Switzerland.
FAU - Escudero, Ian
AU  - Escudero I
AD  - Takeda Vaccines, Singapore.
FAU - Hoffman, Elaine
AU  - Hoffman E
AD  - Takeda Vaccines, Cambridge, MA, USA.
FAU - LeFevre, Inge
AU  - LeFevre I
AD  - Takeda Pharmaceuticals International, Zurich, Switzerland.
FAU - Borkowski, Astrid
AU  - Borkowski A
AD  - Takeda Pharmaceuticals International, Zurich, Switzerland.
FAU - Wallace, Derek
AU  - Wallace D
AD  - Takeda Vaccines, Cambridge, MA, USA.
LA  - eng
SI  - ClinicalTrials.gov/NCT03423173
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20231024
PL  - Netherlands
TA  - Vaccine
JT  - Vaccine
JID - 8406899
RN  - 0 (Dengue Vaccines)
RN  - 0 (Vaccines, Combined)
RN  - 0 (Antibodies, Viral)
RN  - 0 (Antibodies, Neutralizing)
SB  - IM
MH  - Humans
MH  - Adult
MH  - *Dengue/prevention & control
MH  - *Dengue Vaccines
MH  - Vaccines, Combined
MH  - Vaccination/methods
MH  - Double-Blind Method
MH  - Immunogenicity, Vaccine
MH  - Antibodies, Viral
MH  - Antibodies, Neutralizing
OTO - NOTNLM
OT  - Dengue virus
OT  - Immunogenicity
OT  - Reactogenicity
OT  - Safety
OT  - Tetravalent
OT  - Vaccine
COIS- Declaration of Competing Interest The authors declare the following financial 
      interests/personal relationships which may be considered as potential competing 
      interests: VT, MR, IE, EH, IL, AB and DW were employees of the study sponsor at 
      the time of the study. PJW and LMT received fees through their institutions for 
      performing the study.
EDAT- 2023/10/27 00:43
MHDA- 2023/11/03 06:43
CRDT- 2023/10/26 21:54
PHST- 2021/12/01 00:00 [received]
PHST- 2023/09/19 00:00 [revised]
PHST- 2023/09/22 00:00 [accepted]
PHST- 2023/11/03 06:43 [medline]
PHST- 2023/10/27 00:43 [pubmed]
PHST- 2023/10/26 21:54 [entrez]
AID - S0264-410X(23)01132-5 [pii]
AID - 10.1016/j.vaccine.2023.09.049 [doi]
PST - ppublish
SO  - Vaccine. 2023 Nov 13;41(47):6999-7006. doi: 10.1016/j.vaccine.2023.09.049. Epub 
      2023 Oct 24.