RTSS adjuvanted with AS01(London School of Hygiene and Tropical Medicine)(RTSS adjuvanted with AS01(London School of Hygiene and Tropical Medicine))

概要

基本信息

药物类型

预防性疫苗

别名-

靶点-

作用方式

刺激剂

作用机制

免疫刺激剂

治疗领域

感染

在研适应症-

非在研适应症

恶性疟

原研机构

London School of Hygiene & Tropical Medicine

在研机构-

非在研机构

London School of Hygiene & Tropical Medicine

最高研发阶段无进展临床3期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

登录后查看时间轴

关联

2

项与 RTSS adjuvanted with AS01(London School of Hygiene and Tropical Medicine) 相关的临床试验

NCT04319380

/ Completed临床3期IIT

Seasonal Vaccination With the RTS,S/AS01 Malaria Vaccine Given With or Without Seasonal Malaria Chemoprevention: Extension of a Randomised, Double-blind Phase 3 Trial Until Children Reach the Age of Five Years

A double-blind, individual randomised trial will be undertaken in children under five years of age living in areas of Burkina Faso or Mali where the transmission of malaria is intense and highly seasonal to determine whether administration of further doses of the malaria vaccine RTS,S/AS01 at the beginning of the malaria transmission until children reach the age of five years is (a) as effective as SMC with SP + AQ in preventing clinical malaria (b) provides additional, useful protection when given together with SMC. The primary trial end-point will be the incidence of clinical episodes of malaria detected by passive case detection. This is a two year extension of the current RTS,S/AS01 + SMC trial to continue the trial until the study children reach the age of five years, the current age at which SMC is recommended until.

开始日期2020-04-01

申办/合作机构

London School of Hygiene & Tropical Medicine

NCT03143218

/ Completed临床3期IIT

A Phase IIIB Comparative Trial of Seasonal Vaccination With the Malaria Vaccine RTS,S/AS01, Seasonal Malaria Chemoprevention and of the Two Interventions Combined

A double-blind, individual randomised trial will be undertaken in 6000 children under the age of five years living in areas of Burkina Faso or Mali where the transmission of malaria is intense and highly seasonal to determine whether the malaria vaccine RTS,S/AS01 is (a) as effective as SMC with SP + AQ in preventing clinical malaria (b) provides additional, useful protection when given together with SMC. The primary trial end-point will be the incidence of clinical episodes of malaria detected by passive case detection.

开始日期2017-04-17

申办/合作机构

London School of Hygiene & Tropical Medicine

100 项与 RTSS adjuvanted with AS01(London School of Hygiene and Tropical Medicine) 相关的临床结果

登录后查看更多信息

100 项与 RTSS adjuvanted with AS01(London School of Hygiene and Tropical Medicine) 相关的转化医学

登录后查看更多信息

100 项与 RTSS adjuvanted with AS01(London School of Hygiene and Tropical Medicine) 相关的专利（医药）

登录后查看更多信息

153

项与 RTSS adjuvanted with AS01(London School of Hygiene and Tropical Medicine) 相关的文献（医药）

2024-12-01·The Lancet Infectious Diseases

Safety and efficacy of the blood-stage malaria vaccine RH5.1/Matrix-M in Burkina Faso: interim results of a double-blind, randomised, controlled, phase 2b trial in children

Article

作者: Cho, Jee-Sun ; Compaoré, Z Michael John ; Kafando, Miguel ; Daboné, K Carine Sonia ; Bonko, Massa Dit Achille ; Natama, Hamtandi M ; Konaté, Fabé ; Long, Carole A ; Koné, Nadine A ; Tinto, Halidou ; Lawrie, Alison M ; Rouamba, Toussaint ; Sorgho, Hermann ; Salkeld, Jo ; King, Lloyd D W ; Ouédraogo, Florence ; Ouédraogo, Edouard ; Soremekun, Seyi ; Traoré, Ousmane ; Roberts, Rachel ; Shaligram, Umesh ; Pipini, Dimitra ; Draper, Simon J ; Skinner, Katherine ; Minassian, Angela M ; Bradley, John ; Diouf, Ababacar ; Miura, Kazutoyo ; Silk, Sarah E ; Diallo, Salou ; Nielsen, Carolyn M ; Somé, Athanase

BACKGROUNDTwo pre-erythrocytic vaccines (R21/Matrix-M and RTS,S/AS01) are now approved for Plasmodium falciparum malaria. However, neither induces blood-stage immunity against parasites that break through from the liver. RH5.1/Matrix-M, a blood-stage P falciparum malaria vaccine candidate, was highly immunogenic in Tanzanian adults and children. We therefore assessed the safety and efficacy of RH5.1/Matrix-M in Burkinabe children.METHODSIn this double-blind, randomised, controlled, phase 2b trial, RH5.1/Matrix-M was given to children aged 5-17 months in Nanoro, Burkina Faso, a seasonal malaria transmission setting. Children received either three intramuscular vaccinations with 10 μg RH5.1 protein with 50 μg Matrix-M adjuvant or three doses of rabies control vaccine, Rabivax-S, given either in a delayed third-dose (0, 1, and 5 month) regimen (first cohort) or a 0, 1, and 2 month regimen (second cohort). Vaccinations were completed part way through the malaria season. Children were randomly assigned 2:1 within each cohort to receive RH5.1/Matrix-M or Rabivax-S. Participants were assigned according to a random allocation list generated by an independent statistician using block randomisation with variable block sizes. Participants, their families, and the study teams were masked to group allocation; only pharmacists who prepared the vaccines were unmasked. Vaccine safety, immunogenicity, and efficacy were evaluated. The coprimary outcomes assessed were: first, the safety and reactogenicity of RH5.1/Matrix-M; and second, the protective efficacy of RH5.1/Matrix-M against clinical malaria (measured as time to first episode of clinical malaria, using a Cox regression model) from 14 days to 6 months after the third vaccination in the per-protocol sample. This ongoing trial is registered with ClinicalTrials.gov (NCT05790889).FINDINGSFrom April 6 to 13 and July 3 to 7, 2023, 412 children aged 5-17 months were screened, and 51 were excluded. A total of 361 children were enrolled in this study. In the first cohort, 119 were assigned to the RH5.1/Matrix-M delayed third-dose group, and 62 to the equivalent rabies control group. The second cohort included 120 children in the monthly RH5.1/Matrix-M group and 60 in the equivalent rabies control group. The final vaccination was administered to all groups from Sept 4 to 21, 2023. RH5.1/Matrix-M in both cohorts had a favourable safety profile and was well tolerated. Most adverse events were mild, with the most common being local swelling and fever. No serious adverse events were reported. Comparing the RH5.1/Matrix-M delayed third-dose regimen with the pooled control groups resulted in a vaccine efficacy of 55% (95% CI 20 to 75%; p=0·0071). The same analysis showed a vaccine efficacy of 40% (-3 to 65%; p=0·066) when comparing the monthly regimen with the pooled control groups. Participants vaccinated with RH5.1/Matrix-M in both cohorts showed high concentrations of anti-RH5.1 serum IgG antibodies 14 days after the third vaccination, and the purified IgG showed high levels of in vitro growth inhibition activity against P falciparum; these responses were higher in patients who received the RH5.1/Matrix-M vaccine delayed third-dose regimen, as opposed to monthly regimen (growth inhibition activity 79·0% [SD 14·3] vs 74·2% [SD 15·9]; p=0·016).INTERPRETATIONRH5.1/Matrix-M appears safe and highly immunogenic in African children and shows promising efficacy against clinical malaria when given in a delayed third-dose regimen. This trial is ongoing to further monitor efficacy over time.FUNDINGThe European and Developing Countries Clinical Trials Partnership, the UK Medical Research Council, the National Institute for Health and Care Research Oxford Biomedical Research Centre, the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, the US Agency for International Development, and the Wellcome Trust.

2024-11-22·Postgraduate Medical Journal

A new era in malaria prevention: a comparative look at RTS,S/AS01 and R21/Matrix-M vaccines

Article

作者: Al-obeidee, Esraa ; Al-obeidee, Mustafa

2024-10-08·JCI Insight

Identification of RTS,S/AS01 vaccine–induced humoral biomarkers predictive of protection against controlled human malaria infection

Article

作者: Seaton, Kelly E ; Shabbir, Siam ; Deal, Aaron W ; Li, Kan ; Seaton, Kelly E. ; Kisalu, Neville K ; Deal, Aaron W. ; Hilliard, Sir’Tauria ; King, C. Richter ; Spreng, Rachel L ; Mudrak, Sarah V ; Mudrak, Sarah V. ; Gregory, Scott ; Carnacchi, Alexander J ; Kisalu, Neville K. ; King, C Richter ; Horn, Gillian Q. ; Tomaras, Georgia D. ; Dennison, S Moses ; Tomaras, Georgia D ; Horn, Gillian Q ; Dennison, S. Moses ; Abraha, Milite ; Bekker, Valerie ; Mercer, Laina D ; Carnacchi, Alexander J. ; Lin, Lin ; Zhang, Lu ; Mercer, Laina D. ; Hilliard, Sir'Tauria ; Feeney, Elizabeth ; Wille-Reece, Ulrike ; Jongert, Erik ; Dutta, Sheetij ; Spreng, Rachel L.

BACKGROUNDThe mechanism(s) responsible for the efficacy of WHO-recommended malaria vaccine RTS,S/AS01 are not completely understood. We previously identified RTS,S vaccine-induced Plasmodium falciparum circumsporozoite protein-specific (PfCSP-specific) antibody measures associated with protection from controlled human malaria infection (CHMI). Here, we tested the protection-predicting capability of these measures in independent CHMI studies.METHODSVaccine-induced total serum antibody (immunoglobulins, Igs) and subclass antibody (IgG1 and IgG3) responses were measured by biolayer interferometry and the binding antibody multiplex assay, respectively. Immune responses were compared between protected and nonprotected vaccinees using univariate and multivariate logistic regression.RESULTSBlinded prediction analysis showed that 5 antibody binding measures, including magnitude-avidity composite of serum Ig specific for PfCSP, major NANP repeats and N-terminal junction, and PfCSP- and NANP-specific IgG1 subclass magnitude, had good prediction accuracy (area under the receiver operating characteristic curves [ROC AUC] > 0.7) in at least 1 trial. Furthermore, univariate analysis showed a significant association between these antibody measures and protection (odds ratios 2.6-3.1). Multivariate modeling of combined data from 3 RTS,S CHMI trials identified the combination of IgG1 NANP binding magnitude plus serum NANP and N-junction Ig binding magnitude-avidity composite as the best predictor of protection (95% confidence interval for ROC AUC 0.693-0.834).CONCLUSIONThese results reinforce our previous findings and provide a tool for predicting protection in future trials.TRIAL REGISTRATIONClinicalTrials.gov NCT03162614, NCT03824236, NCT01366534, and NCT01857869.FUNDINGThis study was supported by Bill & Melinda Gates Foundation's Global Health-Discovery Collaboratory grants (INV-008612 and INV-043419) to GDT.

100 项与 RTSS adjuvanted with AS01(London School of Hygiene and Tropical Medicine) 相关的药物交易

登录后查看更多信息

研发状态

10 条进展最快的记录,

登录

后查看更多信息

适应症	最高研发状态	国家/地区	公司	日期
恶性疟	临床3期	马里	London School of Hygiene & Tropical Medicine	2017-04-17
恶性疟	临床3期	布基纳法索	London School of Hygiene & Tropical Medicine	2017-04-17

登录后查看更多信息

临床结果

适应症

分期

评价

查看全部结果

研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT04319380 (RTSS-SMC, CTgov)	临床3期	恶性疟	5,098	SMC (SMC With SP+AQ)	衊淵遞膚壓鬱願築淵壓(顧網製廠鹽襯鏇獵蓋築) = 糧願鹽廠願網衊網憲餘願齋選壓餘遞顧願網廠 (糧襯範艱鏇衊艱鹽齋餘, 製窪壓鬱簾鏇淵鹹鹽範 ~ 遞鬱觸壓醖憲餘獵願齋) 更多	-	2024-09-20
				SMC placebo+RTS,S/AS01 (RTS,S/AS01)	衊淵遞膚壓鬱願築淵壓(顧網製廠鹽襯鏇獵蓋築) = 廠顧醖願壓築選膚積遞願齋選壓餘遞顧願網廠 (糧襯範艱鏇衊艱鹽齋餘, 顧鏇憲獵鹽膚鬱觸艱襯 ~ 範夢膚觸淵夢繭顧積膚) 更多
NCT03143218 (RTS,S-SMC \| RTSS-SMC, CTgov)	临床3期	恶性疟	5,920	SP+AQ+RABIPUR® (SMC With SP+AQ)	鹽顧齋築鑰糧餘遞醖顧(鏇糧選鏇積壓餘製夢艱) = 壓願窪鏇簾觸簾遞廠鹹淵襯獵廠鏇艱觸廠積廠 (遞窪膚膚顧築遞製顧窪, 窪鹹鏇觸餘廠餘憲願鹽 ~ 積鬱艱蓋鏇齋糧鹽憲築) 更多	-	2022-01-28
				SMC placebo+RTS,S/AS01 (RTS,S/AS01)	鹽顧齋築鑰糧餘遞醖顧(鏇糧選鏇積壓餘製夢艱) = 壓簾構選選淵顧憲衊鑰淵襯獵廠鏇艱觸廠積廠 (遞窪膚膚顧築遞製顧窪, 簾襯鑰網構窪繭醖襯網 ~ 夢繭繭顧淵顧選衊網鹽) 更多