Consistency of immunogenicity in three consecutive lots of a tetravalent dengue vaccine candidate (TAK-003): A randomized placebo-controlled trial in US adults.

Autor: Tricou V; Takeda Pharmaceuticals International, Zurich, Switzerland. Electronic address: vianney.tricou@takeda.com., Winkle PJ; Anaheim Clinical Trials, Anaheim, CA, USA., Tharenos LM; Synexus - St. Louis, St. Louis, MO, USA., Rauscher M; Takeda Pharmaceuticals International, Zurich, Switzerland., Escudero I; Takeda Vaccines, Singapore., Hoffman E; Takeda Vaccines, Cambridge, MA, USA., LeFevre I; Takeda Pharmaceuticals International, Zurich, Switzerland., Borkowski A; Takeda Pharmaceuticals International, Zurich, Switzerland., Wallace D; Takeda Vaccines, Cambridge, MA, USA.
Jazyk: angličtina
Zdroj: Vaccine [Vaccine] 2023 Nov 13; Vol. 41 (47), pp. 6999-7006. Date of Electronic Publication: 2023 Oct 24.
DOI: 10.1016/j.vaccine.2023.09.049
Abstrakt: 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.
Competing Interests: 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.
(Copyright © 2023 Takeda Vaccines. Published by Elsevier Ltd.. All rights reserved.)
Databáze: MEDLINE
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