Abstract
Post kala azar dermal leishmaniasis (PKDL) is a chronic, stigmatising skin condition occurring frequently after apparent clinical cure from visceral leishmaniasis. Given an urgent need for new treatments, we conducted a Phase IIa safety and immunogenicity trial of ChAd63-KH vaccine in Sudanese patients with persistent PKDL. LEISH2a (NCT02894008) was an open label three-phase clinical trial involving sixteen adult and eight adolescent patients with persistent PKDL (median duration 30 months; range 6 -180 months). Patients received a single intramuscular vaccination of 1×1010 viral particles (v.p.; adults only) or 7.5×1010 v.p. (adults and adolescents), with primary (safety) and secondary (clinical response and immunogenicity) endpoints evaluated over 42-120 days follow up. AmBisome® was provided to patients with significant remaining disease at their last visit. ChAd63-KH vaccine showed minimal adverse reactions in PKDL patients and induced potent innate and cell-mediated immune responses measured by whole blood transcriptomics and ELISpot. 7 patients (30.4%) monitored to study completion showed >90% clinical improvement and 6 (25%) showed partial improvement. A logistic regression model applied to blood transcriptomic data identified immune modules predictive of patients with >90% clinical improvement. A randomised controlled trial to determine whether these clinical responses were vaccine related and whether ChAd63-KH vaccine has clinical utility is underway.
Competing Interest Statement
CL, PMK and TA are co-authors of a patent protecting the gene insert used in candidate vaccine ChAd63-KH (Europe 10719953.1; India 315101). The authors otherwise declare no competing interests.
Clinical Trial
NCT02894008
Funding Statement
The clinical trial was funded by a Wellcome Trust Translation Award (WT108518MA; https://wellcome.ac.uk). Additional support for immunological studies was provided by a Wellcome Trust Senior Investigator Award (to PMK; WT104726) and by the TRANSVAC2 program supported by the European Union Horizon 2020 Research and Innovation programme under grant agreement No. 730964 (TNA1802-02; https://www.transvac.org). The funders played no role in study design or decision to publish.
Author Declarations
I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.
Yes
The details of the IRB/oversight body that provided approval or exemption for the research described are given below:
The study was approved by the Review Committees of the Institute of Endemic Diseases, University of Khartoum, the Sudan National Medicines and Poisons Board and the Department of Biology, University of York. LEISH2a was sponsored by the University of York. The study was conducted according to the principles of the current revision of the Declaration of Helsinki 2008 and ICH guidelines for GCP (CPMP/ICH/135/95) and was registered as NCT02894008 at ClinicalTrials.gov. All participants provided written informed consent before enrolment.
All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.
Yes
I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).
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I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.
Yes
Data Availability
Transcriptomic data have been deposited in the Gene Expression Omnibus (GEO) repository with accession number GSE156645 and are available from: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE156645.
https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE156645