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.

Start Date06 Apr 2020

Sponsor / Collaborator

The University of York

100 Clinical Results associated with ChAd63-KH(The University of York)

100 Translational Medicine associated with ChAd63-KH(The University of York)

100 Patents (Medical) associated with ChAd63-KH(The University of York)

Literatures (Medical) associated with ChAd63-KH(The University of York)

01 Sep 2024·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

Author: 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 ; Khalil, Eltahir A G ; Lacey, Charles J N ; 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

Author: 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 ONEQ3 · CROSS-FIELD

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

Q3 · CROSS-FIELD

ArticleOA

Author: Katie J. Ewer ; Sarah Moyle ; Alfredo Nicosia ; Tabitha Mahungu ; Fenella D. Halstead ; Katherine Gantlett ; Sean C. Elias ; Susanne H. Sheehy ; Tom Doherty ; 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 Deals associated with ChAd63-KH(The University of York)

R&D Status

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Indication	Highest Phase	Country/Location	Organization	Date
Post-Kala-azar dermal leishmanioid	Phase 2	SD	The University of York	06 Apr 2020

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03969134 (Pubmed \| Mol Ther Methods Clin Dev) Manual	Phase 2	Post-Kala-azar dermal leishmanioid	86	ChAd63-KH	(hkigvjtxkz) = kqadxqlggd bupkvcehob (pniysvptfy )	Negative	01 Sep 2024
				Placebo	(hkigvjtxkz) = dnoaamquzh bupkvcehob (pniysvptfy )

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