A Phase 1/2, Randomized, Observer-blind Study of Varying Injection Schedules of a Tetravalent Dengue Virus Purified Inactivated Vaccine (TDENV-PIV) With AS03B Adjuvant and Placebo in Healthy Adults in the US

This study is being conducted to evaluate the safety and immunogenicity and antibody persistence of the candidate dengue vaccine.

开始日期2015-08-01

申办/合作机构

U S Army Medical Research & Development Command

[+2]

NCT01702857 / Completed临床1期IIT

A Phase I, Randomized, Placebo-Controlled, Observer-blind, Two-dose (0-28 Day Schedule) Primary Vaccination Study of WRAIR Tetravalent Dengue Virus Purified Inactivated Vaccine (TDENV-PIV) in Healthy Adults in Puerto Rico

This is a first time in humans (FTiH) study designed to assess the experimental TDENV-PIV vaccine in a predominantly dengue-primed adult population. The study is designed to afford a first time in humans (FTiH) safety and immunogenicity assessment of three TDENV-PIV vaccine candidates, each formulated with a different adjuvant: either aluminum hydroxide, AS01E or AS03B (adjuvants used in GSK Biologicals' hepatitis B candidate vaccine, malaria candidate vaccine and pandemic flu vaccine, respectively). Each vaccine candidate will contain 1 µg of purified virus antigen per each of the four DENV types. Additionally, the study will evaluate an alum adjuvanted TDENV-PIV vaccine candidate containing 4 µg of purified virus antigen per each of the four DENV types. The control group will receive a saline placebo. All experimental vaccinations will be administered according to a 2-dose schedule, 28 days apart. There is a parallel FTiH study that is conducted in the United States in a dengue-naive population using the same investigational vaccines.

开始日期2012-11-01

申办/合作机构

U S Army Medical Research & Development Command

[+2]

NCT01666652 / Completed临床1期IIT

A Phase I, Randomized, Placebo-Controlled, Observer-blind, Two-dose (0-28 Day Schedule) Primary Vaccination Study of Walter Reed Army Institute of Research (WRAIR) Tetravalent Dengue Virus Purified Inactivated Vaccine (TDENV-PIV) in Healthy Adults in a Non-Endemic Region

The study is designed to afford a safety and immunogenicity assessment of three Tetravalent Dengue Virus-Purified Inactivated Vaccine(TDENV-PIV) vaccine candidates.

开始日期2012-09-01

申办/合作机构

U S Army Medical Research & Development Command

[+2]

100 项与 Tetravalent dengue virus purified inactivated vaccine with alum adjuvant(Walter Reed Army Institute of Research) 相关的临床结果

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100 项与 Tetravalent dengue virus purified inactivated vaccine with alum adjuvant(Walter Reed Army Institute of Research) 相关的转化医学

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100 项与 Tetravalent dengue virus purified inactivated vaccine with alum adjuvant(Walter Reed Army Institute of Research) 相关的专利（医药）

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项与 Tetravalent dengue virus purified inactivated vaccine with alum adjuvant(Walter Reed Army Institute of Research) 相关的文献（医药）

2024-08-01·The Lancet Infectious Diseases

Efficacy and immunogenicity following dengue virus-1 human challenge after a tetravalent prime-boost dengue vaccine regimen: an open-label, phase 1 trial

Article

作者: Chua, Joel V ; Rapaka, Rekha R ; Gutierrez-Barbosa, Hernando ; Waickman, Adam T ; McCracken, Michael K ; Currier, Jeffrey R ; Koren, Michael ; De La Barrera, Rafael A ; Jarman, Richard G ; Joshi, Sudhaunshu ; Bernal, Paula ; Gromowski, Gregory D ; Shrestha, Biraj ; Lyke, Kirsten E ; Culbertson, Christopher ; Edelman, Robert ; Strauss, Kathleen ; Friberg, Heather

BACKGROUNDDengue human infection models (DHIMs) are important tools to down-select dengue vaccine candidates and establish tetravalent efficacy before advanced clinical field trials. We aimed to provide data for the safety and immunogenicity of DHIM and evaluate dengue vaccine efficacy.METHODSWe performed an open-label, phase 1 trial at the University of Maryland (Baltimore, MD, USA). Eligible participants were healthy individuals aged 18-50 years who either previously received a tetravalent dengue purified inactivated vaccine prime followed by a live-attenuated vaccine boost (ie, the vaccinee group), or were unvaccinated flavivirus-naive participants (ie, the control group). Participants in the vaccinee group with detectable pre-challenge dengue virus-1 neutralising antibody titres and flavivirus-naive participants in the control group were inoculated with dengue virus-1 strain 45AZ5 in the deltoid region, 27-65 months following booster dosing. These participants were followed-up from days 4-16 following dengue virus-1 live virus human challenge, with daily real-time quantitative PCR specific to dengue virus-1 RNA detection, and dengue virus-1 solicited local and systemic adverse events were recorded. The primary outcomes were safety (ie, solicited local and systemic adverse events) and vaccine efficacy (ie, dengue virus-1 RNAaemia) following dengue challenge. This study is registered with ClinicalTrials.gov, number NCT04786457.FINDINGSIn January 2021, ten eligible participants were enrolled; of whom, six (60%) were in the vaccinee group and four (40%) were in the control group. Daily quantitative PCR detected dengue virus-1 RNA in nine (90%) of ten participants (five [83%] of six in the vaccinee group and all four [100%] in the control group). The mean onset of RNAaemia occurred on day 5 (SD 1·0) in the vaccinee group versus day 8 (1·5) in the control group (95% CI 1·1-4·9; p=0·007), with a trend towards reduced RNAaemia duration in the vaccinee group compared with the control group (8·2 days vs 10·5 days; 95% CI -0·08 to 4·68; p=0·056). Mild-to-moderate symptoms (nine [90%] of ten), leukopenia (eight [89%] of nine), and elevated aminotransferases (seven [78%] of nine) were commonly observed. Severe adverse events were detected only in the vaccinee group (fever ≥38·9°C in three [50%] of six, headache in one [17%], and transient grade 4 aspartate aminotransferase elevation in one [17%]). No deaths were reported.INTERPRETATIONParticipants who had tetravalent dengue purified inactivated vaccine prime and live-attenuated vaccine boost were unprotected against dengue virus-1 infection and further showed increased clinical, immunological, and transcriptomic evidence for inflammation potentially mediated by pre-existing infection-enhancing antibodies. This study highlights the impact of small cohort, human challenge models studying dengue pathogenesis and downstream vaccine development.FUNDINGMilitary Infectious Disease Research Program and Medical Technology Enterprise Consortium and Advanced Technology International.

2021-05-28·The Journal of Infectious Diseases2区 · 医学

Immunogenicity of a Live-Attenuated Dengue Vaccine Using a Heterologous Prime-Boost Strategy in a Phase 1 Randomized Clinical Trial

2区 · 医学

Article

作者: Lin, Leyi ; Thomas, Stephen J ; Friberg, Heather ; Endy, Timothy P ; Paolino, Kristopher M ; Jasper, Louis E ; Jarman, Richard G ; Gromowski, Gregory D ; Currier, Jeffrey R ; Sondergaard, Erica L ; Keiser, Paul B ; De La Barrera, Rafael ; Sklar, Marvin J ; Koren, Michael A ; Aronson, Naomi E ; Eckels, Kenneth H

AbstractBackgroundDengue is a global health problem and the development of a tetravalent dengue vaccine with durable protection is a high priority. A heterologous prime-boost strategy has the advantage of eliciting immune responses through different mechanisms and therefore may be superior to homologous prime-boost strategies for generating durable tetravalent immunity.MethodsIn this phase 1 first-in-human heterologous prime-boost study, 80 volunteers were assigned to 4 groups and received a tetravalent dengue virus (DENV-1–4) purified inactivated vaccine (TDENV-PIV) with alum adjuvant and a tetravalent dengue virus (DENV-1–4) live attenuated vaccine (TDENV-LAV) in different orders and dosing schedules (28 or 180 days apart).ResultsAll vaccination regimens had acceptable safety profiles and there were no vaccine-related serious adverse events. TDEN-PIV followed by TDEN-LAV induced higher neutralizing antibody titers and a higher rate of tetravalent seroconversions compared to TDEN-LAV followed by TDEN-PIV. Both TDEN-PIV followed by TDEN-LAV groups demonstrated 100% tetravalent seroconversion 28 days following the booster dose, which was maintained for most of these subjects through the day 180 measurement.ConclusionsA heterologous prime-boost vaccination strategy for dengue merits additional evaluation for safety, immunogenicity, and potential for clinical benefit.Clinical Trials RegistrationNCT02239614.

2018-05-09·The American Journal of Tropical Medicine and Hygiene4区 · 医学

Phase I Randomized Study of a Tetravalent Dengue Purified Inactivated Vaccine in Healthy Adults from Puerto Rico

4区 · 医学

Article

作者: Campos, Maribel ; De La Barrera, Rafael ; Schmidt, Alexander C. ; Lepine, Edith ; Lin, Leyi ; Innis, Bruce L. ; Thomas, Stephen J. ; Martinez, Luis J. ; Toussaint, Jean-François ; Diaz, Clemente ; Eckels, Kenneth H. ; Jarman, Richard G. ; Febo, Irma

The safety and immunogenicity of four adjuvanted formulations of an investigational tetravalent dengue purified inactivated vaccine (DPIV) were evaluated in a predominantly dengue-primed population in Puerto Rico. In this placebo-controlled, randomized, observer-blind, phase I trial, 100 healthy adults were randomized 1:1:1:1:1 to receive DPIV at Day (D)0 and D28 (1 μg per dengue virus [DENV] type 1–4 adjuvanted with either alum, AS01E or AS03B, or 4 μg per DENV type adjuvanted with alum) or saline placebo. Functional antibody responses were assessed using a microneutralization assay at D56, Month (M)7, and M13. All DPIV formulations were well tolerated and no safety signals were identified through M13. The M13 according-to-protocol (ATP) immunogenicity cohort included 83 participants. The ATP analysis of immunogenicity was performed only on the 78 subjects seropositive for ≥ 1 DENV type at baseline: 69 tetravalent, three trivalent, two bivalent, and four monovalent. In all DPIV groups, geometric mean antibody titers (GMTs) increased from D0 to D56 and waned modestly through M13, while remaining well above prevaccination levels. The 4 μg + alum and the AS01E- and AS03B-adjuvanted formulations were highly immunogenic, with M13-neutralizing antibody GMTs against all four DENV types above 1,000. M13/D0 GMT ratios were highest in the 1 μg + AS03B group (ranging 3.2–3.7 depending on the DENV type). These results encourage continued clinical development of DPIV (ClinicalTrials.gov: NCT01702857).

100 项与 Tetravalent dengue virus purified inactivated vaccine with alum adjuvant(Walter Reed Army Institute of Research) 相关的药物交易

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研发状态

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适应症	最高研发状态	国家/地区	公司	日期
登革热	临床2期	-	Walter Reed Army Institute of Research	-
登革热	临床2期	-	United States Army Medical Research and Materiel Command	-
登革热	临床2期	-	GSK Plc	-

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT01666652 (DPIV-001, CTgov)	临床1期	登革热	100	alum adjuvant (TDENV-PIV alum1)	艱淵繭願鑰齋簾築襯願(範齋製獵襯餘繭鏇蓋廠) = 遞觸窪膚遞範壓鏇廠壓積築餘廠夢遞網醖齋蓋 (鏇簾衊艱齋觸壓鏇膚餘, 觸齋膚襯簾艱鹽鑰醖窪 ~ 衊襯獵廠憲憲淵齋網顧) 更多	-	2019-01-25
				4 µg TDENV-PIV (TDENV-PIV alum4)	艱淵繭願鑰齋簾築襯願(範齋製獵襯餘繭鏇蓋廠) = 選鏇艱鬱壓鬱壓蓋築願積築餘廠夢遞網醖齋蓋 (鏇簾衊艱齋觸壓鏇膚餘, 鹽蓋網選憲積觸獵蓋鑰 ~ 觸糧網繭夢範選壓製襯) 更多