This trial is designed to assess the therapeutic efficacy and safety of CHAd63-KH, a new candidate Leishmania vaccine, in patients with persistent PKDL. 100 participants will be randomly assigned (50 participants in each arm) to receive placebo or ChAd63-KH 7.5 x10(10)vp. Doses will be administered at a single time point.

开始日期2020-04-06

申办/合作机构

The University of York

100 项与 ChAd63-KH(The University of York) 相关的临床结果

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100 项与 ChAd63-KH(The University of York) 相关的转化医学

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100 项与 ChAd63-KH(The University of York) 相关的专利（医药）

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项与 ChAd63-KH(The University of York) 相关的文献（医药）

2024-09-01·Molecular Therapy - Methods & Clinical Development

A randomized, double-blind phase 2b trial to evaluate efficacy of ChAd63-KH for treatment of post kala-azar dermal leishmaniasis

Article

作者: Montesi, Giorgio ; Kaye, Paul M. ; Osman, Mohamed ; Khalil, Eltahir A.G. ; Suliman, Ahmed J. ; Younis, Brima M. ; Keding, Ada ; Younis, Brima M ; Saeed, Mohammed ; Lacey, Charles J.N. ; Santoro, Francesco ; Elmukashfi, Elmukashfi T A ; Suliman, Ahmed J ; Layton, Alison M. ; Novedrati, Maria ; Musa, Amin E.A. ; Elmukashfi, Elmukashfi T.A. ; Wiggins, Rebecca ; Alamin, Mohammed ; Noureldein, Ali ; Sonnati, Chiara ; Musa, Ahmed M ; Kaye, Paul M ; Salman, Khalid ; Musa, Amin E A ; Layton, Alison M ; Mustafa, Ala Eldin ; Lacey, Charles J N ; Khalil, Eltahir A G ; Musa, Ahmed M.

In a recent phase 2a clinical trial, the candidate leishmaniasis vaccine ChAd63-KH was shown to be safe and immunogenic in Sudanese patients with post kala-azar dermal leishmaniasis (PKDL). However, its value as a stand-alone therapeutic was unknown. To assess the therapeutic efficacy of ChAd63-KH, we conducted a randomized, double-blind, placebo-controlled phase 2b trial (ClinicalTrials.gov: NCT03969134). Primary outcomes were safety and efficacy (≥90% improvement in clinical disease). Secondary outcomes were change in severity grade and vaccine-induced immune response. 86 participants with uncomplicated PKDL of ≥6 month duration were randomized to receive ChAd63-KH (7.5 × 10¹⁰ viral particles, once by the intramuscular route) or placebo. 75 participants (87%) completed the trial as per protocol. No severe or serious adverse events were observed. At day 90 post-vaccination, 6/40 (15%) and 4/35 (11%) participants in the vaccine and placebo groups, respectively, showed ≥90% clinical improvement (risk ratio [RR] 1.31 [95% confidence interval (CI), 0.40-4.28], p = 0.742). There were also no significant differences in PKDL severity grade between study arms. Whole-blood transcriptomic analysis identified transcriptional modules associated with interferon responses and monocyte and dendritic cell activation. Thus, a single vaccination with ChAd63-KH showed no therapeutic efficacy in this subset of Sudanese patients with PKDL.

Pathogens

Advances in Leishmania Vaccines: Current Development and Future Prospects

Review

作者: Llanes, Alejandro ; Restrepo, Carlos M. ; Lleonart, Ricardo ; Ayala, Andreina

Leishmaniasis is a neglected tropical disease caused by parasites of the genus Leishmania. As approved human vaccines are not available, treatment and prevention rely heavily on toxic chemotherapeutic agents, which face increasing resistance problems. The development of effective vaccines against human leishmaniasis is of utmost importance for the control of the disease. Strategies that have been considered for this purpose range from whole-killed and attenuated parasites to recombinant proteins and DNA vaccines. The ideal vaccine must be safe and effective, ensuring lasting immunity through a robust IL-12-driven Th1 adaptive immune response. Despite some success and years of effort, human vaccine trials have encountered difficulties in conferring durable protection against Leishmania, a problem that may be attributed to the parasite’s antigenic diversity and the intricate nature of the host’s immune response. The aim of this review is to provide a thorough overview of recent advances in Leishmania vaccine development, ranging from initial trials to recent achievements, such as the ChAd63-KH DNA vaccine, which underscores the potential for effective control of leishmaniasis through continued research in this field.

PLoS ONE3区 · 综合性期刊

Phase Ia Clinical Evaluation of the Safety and Immunogenicity of the Plasmodium falciparum Blood-Stage Antigen AMA1 in ChAd63 and MVA Vaccine Vectors

3区 · 综合性期刊

ArticleOA

作者: Katie J. Ewer ; Sarah Moyle ; Alfredo Nicosia ; Tabitha Mahungu ; Fenella D. Halstead ; Katherine Gantlett ; Sean C. Elias ; Tom Doherty ; Susanne H. Sheehy ; Simon J. Draper ; Sarah C. Gilbert ; Matthew D. J. Dicks ; Stefano Colloca ; Riccardo Cortese ; Carole A. Long ; Alison M. Lawrie ; Katharine A. Collins ; Ian D. Poulton ; Geraldine A. O'Hara ; Eleanor Berrie ; Alexandra J. Spencer ; Adrian V. S. Hill ; Nick J. Edwards ; Christopher J. A. Duncan ; Sumi Biswas ; Kazutoyo Miura

BACKGROUNDTraditionally, vaccine development against the blood-stage of Plasmodium falciparum infection has focused on recombinant protein-adjuvant formulations in order to induce high-titer growth-inhibitory antibody responses. However, to date no such vaccine encoding a blood-stage antigen(s) alone has induced significant protective efficacy against erythrocytic-stage infection in a pre-specified primary endpoint of a Phase IIa/b clinical trial designed to assess vaccine efficacy. Cell-mediated responses, acting in conjunction with functional antibodies, may be necessary for immunity against blood-stage P. falciparum. The development of a vaccine that could induce both cell-mediated and humoral immune responses would enable important proof-of-concept efficacy studies to be undertaken to address this question.METHODOLOGYWe conducted a Phase Ia, non-randomized clinical trial in 16 healthy, malaria-naïve adults of the chimpanzee adenovirus 63 (ChAd63) and modified vaccinia virus Ankara (MVA) replication-deficient viral vectored vaccines encoding two alleles (3D7 and FVO) of the P. falciparum blood-stage malaria antigen; apical membrane antigen 1 (AMA1). ChAd63-MVA AMA1 administered in a heterologous prime-boost regime was shown to be safe and immunogenic, inducing high-level T cell responses to both alleles 3D7 (median 2036 SFU/million PBMC) and FVO (median 1539 SFU/million PBMC), with a mixed CD4(+)/CD8(+) phenotype, as well as substantial AMA1-specific serum IgG responses (medians of 49 µg/mL and 41 µg/mL for 3D7 and FVO AMA1 respectively) that demonstrated growth inhibitory activity in vitro.CONCLUSIONSChAd63-MVA is a safe and highly immunogenic delivery platform for both alleles of the AMA1 antigen in humans which warrants further efficacy testing. ChAd63-MVA is a promising heterologous prime-boost vaccine strategy that could be applied to numerous other diseases where strong cellular and humoral immune responses are required for protection.TRIAL REGISTRATIONClinicalTrials.gov NCT01095055.

100 项与 ChAd63-KH(The University of York) 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
黑热病后皮肤利什曼原虫	临床2期	苏丹	The University of York	2020-04-06

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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


NCT03969134 (Pubmed \| Mol Ther Methods Clin Dev) 人工标引	临床2期	黑热病后皮肤利什曼原虫	86	ChAd63-KH	(艱製廠鑰膚繭獵遞醖艱) = 築窪簾窪膚艱壓艱鹽鑰膚糧構廠顧築積鏇艱廠 (蓋鏇窪糧積築憲築鹹鬱 )	不佳	2024-09-01
				Placebo	(艱製廠鑰膚繭獵遞醖艱) = 齋選選鹽製製鹽鏇範艱膚糧構廠顧築積鏇艱廠 (蓋鏇窪糧積築憲築鹹鬱 )