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LEISH2b - A phase 2b study to assess the safety, efficacy, and immunogenicity of the Leishmania vaccine ChAd63-KH in post-kala azar dermal leishmaniasis.

作者信息

Lacey Charles, Musa Ahmed, Khalil El Tahir, Younis Brima, Osman Mohamed, Wiggins Rebecca, Keding Ada, Kaye Paul

机构信息

York Biomedical Research Institute, University of York, UK, York, UK.

Institute of Endemic Diseases, University of Khartoum, Khartoum, Sudan.

出版信息

Wellcome Open Res. 2022 Aug 3;7:200. doi: 10.12688/wellcomeopenres.17951.1. eCollection 2022.


DOI:10.12688/wellcomeopenres.17951.1
PMID:37252616
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10213822/
Abstract

The leishmaniases are neglected tropical diseases caused by various parasite species transmitted by sand flies. They comprise a number of systemic and cutaneous syndromes including kala-azar (visceral leishmaniasis, VL), cutaneous leishmaniasis (CL), and post-kala-azar dermal leishmaniasis (PKDL). The leishmaniases cause significant mortality (estimated 20 - 50,000 deaths annually), morbidity, psychological sequelae, and healthcare and societal costs. Treatment modalities remain difficult. E.g., East African PKDL requires 20 days of intravenous therapy, and frequently relapsing VL is seen in the setting of HIV and immunodeficiency. We developed a new therapeutic vaccine, ChAd63-KH for VL / CL / PKDL and showed it to be safe and immunogenic in a phase 1 trial in the UK, and in a phase 2a trial in PKDL patients in Sudan.    This is a randomised double-blind placebo-controlled phase 2b trial to assess the therapeutic efficacy and safety of ChAd63-KH in patients with persistent PKDL in Sudan. 100 participants will be randomly assigned 1:1 to receive placebo or ChAd63-KH (7.5 x10 vp i.m.) at a single time point. Follow up is for 120 days after dosing and we will compare the clinical evolution of PKDL, as well as the humoral and cellular immune responses between the two arms. Successful development of a therapeutic vaccine for leishmaniasis would have wide-ranging direct and indirect healthcare benefits that could be realized rapidly. For PKDL patients, an effective therapeutic vaccination used alone   would have very significant clinical value, reducing the need for extensive hospitalization and chemotherapy. Combining vaccine with drug (immuno-chemotherapy) might significantly increase the effective life of new drugs, with lower dose / abbreviated regimens helping to limit the emergence of drug resistance. If therapeutic benefit of ChAd63-KH can be shown in PKDL further evaluation of the vaccine in other forms of leishmaniasis should be considered. NCT03969134.

摘要

相似文献

[1]
LEISH2b - A phase 2b study to assess the safety, efficacy, and immunogenicity of the Leishmania vaccine ChAd63-KH in post-kala azar dermal leishmaniasis.

Wellcome Open Res. 2022-8-3

[2]
A third generation vaccine for human visceral leishmaniasis and post kala azar dermal leishmaniasis: First-in-human trial of ChAd63-KH.

PLoS Negl Trop Dis. 2017-5-12

[3]
A randomized, double-blind phase 2b trial to evaluate efficacy of ChAd63-KH for treatment of post kala-azar dermal leishmaniasis.

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[4]
Safety and immunogenicity of ChAd63-KH vaccine in post-kala-azar dermal leishmaniasis patients in Sudan.

Mol Ther. 2021-7-7

[5]
Consultation meeting on the development of therapeutic vaccines for post kala azar dermal leishmaniasis.

Kinetoplastid Biol Dis. 2007-8-17

[6]
PKDL and other dermal lesions in HIV co-infected patients with Leishmaniasis: review of clinical presentation in relation to immune responses.

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[7]
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[8]
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[9]
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[10]
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[1]
Unravelling drug resistance in leishmaniasis: genomic adaptations and emerging therapies.

Front Mol Biosci. 2025-5-26

[2]
An update on recombinant vaccines against leishmaniasis.

Indian J Med Res. 2024

[3]
Advances in Vaccines: Current Development and Future Prospects.

Pathogens. 2024-9-20

[4]
A randomized, double-blind phase 2b trial to evaluate efficacy of ChAd63-KH for treatment of post kala-azar dermal leishmaniasis.

Mol Ther Methods Clin Dev. 2024-7-30

[5]
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[6]
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[7]
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Korean J Parasitol. 2022-12

本文引用的文献

[1]
COVID-19 Vaccines: Adenoviral Vectors.

Annu Rev Med. 2022-1-27

[2]
Safety and immunogenicity of ChAd63-KH vaccine in post-kala-azar dermal leishmaniasis patients in Sudan.

Mol Ther. 2021-7-7

[3]
The potential impact of human visceral leishmaniasis vaccines on population incidence.

PLoS Negl Trop Dis. 2020-7-2

[4]
Post kala-azar dermal leishmaniasis: A threat to elimination program.

PLoS Negl Trop Dis. 2020-7-2

[5]
Host transcriptomic signature as alternative test-of-cure in visceral leishmaniasis patients co-infected with HIV.

EBioMedicine. 2020-5

[6]
Quantifying the Infectiousness of Post-Kala-Azar Dermal Leishmaniasis Toward Sand Flies.

Clin Infect Dis. 2019-7-2

[7]
Knowledge, stigma, health seeking behaviour and its determinants among patients with post kalaazar dermal leishmaniasis, Bihar, India.

PLoS One. 2018-9-7

[8]
Monitoring of Parasite Kinetics in Indian Post-Kala-azar Dermal Leishmaniasis.

Clin Infect Dis. 2018-1-18

[9]
A third generation vaccine for human visceral leishmaniasis and post kala azar dermal leishmaniasis: First-in-human trial of ChAd63-KH.

PLoS Negl Trop Dis. 2017-5-12

[10]
Post kala-azar dermal leishmaniasis: an unresolved mystery.

Trends Parasitol. 2014-1-2

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