A Study to Assess Safety and Efficacy of a Leishmania Vaccine to Prevent Post Kala Azar Dermal Leishmaniasis (PKDL) (LEISH3)

A Phase II Study to Assess the Safety and Efficacy of the Leishmania Vaccine ChAd63-KH for the Prevention of Post-kala Azar Dermal Leishmaniasis

The actual format of the anticipated LEISH3 trial is under review.

Study Overview

• Status: Withdrawn
• Conditions: Post-kala-azar Dermal Leishmaniasis
• Intervention / Treatment: Biological: Vaccine; Other: Placebo

Detailed Description

The leishmaniases are poverty-related neglected diseases with a major impact on health worldwide. They affect the poorest of the poor and present a severe barrier to socio-economic development. Caused by infection with one of several species of Leishmania parasite, these diseases occur in 98 countries worldwide and can be broadly classified as tegumentary leishmaniases (TL; affecting the skin and mucosa) and visceral leishmaniasis (VL; affecting internal organs). Worldwide, over 1 million reported cases of TL and 0.5 million reported cases of VL occur each year. Whereas TL are chronic and non-life-threatening, VL is responsible for over 20,000 deaths per year, second only to malaria amongst parasites with regard to mortality. Collectively, approximately 2.4 million disability-adjusted life years are lost to the leishmaniases. No vaccines are currently licensed for any form of human leishmaniasis and the drug arsenal is limited and increasingly compromised by drug resistance.

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• Study Type: Interventional
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years to 48 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

The patient volunteer must be:

• Aged 12 to 50 years on the day of screening
• Have had VL and have been cured following a standard regimen of SSG / PM
• Females must be unmarried, single, or widowed
• Willing and able to give written informed consent
• For adolescents aged 12 to 17 years on the day of screening written informed consent from a parent must be obtained.

All Participants

• Uncomplicated VL responsive to SSG / PM treatment
• Have relatively normal blood values in the setting of VL, defined as hemoglobin >5.0 g/dL, white blood cells >1.0 x10(9)/L, platelets >40 x10(9)/L, liver function tests < x5 normal, Creatinine <1.5 mg/dL
• Available for the duration of the study
• Without any other significant health problems as determined by medical history, physical examination, results of screening tests and the clinical judgment of a medically qualified Clinical Investigator
• Negative for malaria on blood smear
• Judged, in the opinion of a medically qualified Clinical Investigator, to be able and likely to comply with all study requirements as set out in the protocol
• Negative for human immunodeficiency virus (HIV), Hepatitis B and Hepatitis C
• For females only, willing to undergo urinary pregnancy tests on the day of screening, on the day of vaccination (prior to vaccination) and 3, 6, 9 and 12 months after vaccination.

Exclusion Criteria:

The volunteer may not enter the study if any of the following apply:

• Has HIV/VL coinfection
• Has had previous treatment for VL with relapse
• Receipt of a live attenuated vaccine within 60 days or other vaccine within 14 days of screening
• Administration of immunoglobulins and/or any blood products within the three months preceding the planned administration of the vaccine candidate
• History of allergic disease or reactions likely to be exacerbated by any component of the vaccine or a history of severe or multiple allergies to drugs or pharmaceutical agents
• Any history of severe local or general reaction to vaccination as defined as
• Local: extensive, indurated redness and swelling involving most of the antero-lateral thigh or the major circumference of the arm, not resolving within 72 hours
• General: fever ≥ 39.5°C within 48 hours, anaphylaxis, bronchospasm, laryngeal oedema, collapse, convulsions or encephalopathy within 48 hours
• Females - pregnancy, less than 12 weeks postpartum, lactating or willingness/intention to become pregnant during the study and for 3 months following vaccination.
• Seropositive for hepatitis B surface antigen (HBsAg) or Hepatitis C (antibodies to hepatitis C virus)
• Significant abnormal finding (in the setting of VL, see definitions in Inclusion criteria) on entry biochemistry or haematology blood tests or urinalysis
• Any confirmed or suspected immunosuppressive or immunodeficient state, including HIV infection; asplenia; recurrent, severe infections and chronic (more than 14 days) immunosuppressant medication within the past 6 months
• Tuberculosis, leprosy, or malnutrition (malnutrition in adults defined as a BMI <18.5, and in adolescents (12-17yrs) as a Z score cut-off value of <-2 SD).
• Any other significant disease, disorder or finding, which, in the opinion of a medically qualified Clinical Investigator, may either put the volunteer at risk because of participation in the study, or may influence the result of the study, or the volunteer's ability to participate in the study
• Unlikely to comply with the study protocol

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Vaccine arm; Vaccine in 1 ml, single dose	Biological: Vaccine; Single intramuscular injection into the deltoid region; Other Names: ChAd63-KH
Placebo Comparator: Placebo; 1 ml normal saline , single dose	Other: Placebo; Single intramuscular injection into the deltoid region

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety of single dose vaccination with ChAd63-KH	Treatment-related adverse events as defined in the clinical trial protocol (median no. events)	12 months from vaccination
Efficacy of single dose vaccination with ChAd63-KH	Frequency of occurrence of PKDL in patients completing treatment with SSG / PM.	12 months from vaccination

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immunological response: T cells	To compare systemic immune responses in vaccine vs placebo arms by measurement of the frequency (median) of gamma-interferon producing T cells	12 months from vaccination
Immunological response: transcriptomics	Comparing transcripts for differential expression in vaccine and placebo arms	12 months from vaccination
Pathogenesis of PKDL comparing Leishmania parasite load pre-vaccination and at PKDL onset	Parasite detection using RNAscope / immunocytochemistry	12 months from vaccination
Immunological response: B cells	Measurement of frequency in vaccinated and placebo groups of B cells by flow cytometry	12 months from vaccination
Immunological response: antibody levels	To compare systemic immune responses in vaccine vs placebo arms by median optical density levels	12 months from vaccination

Collaborators and Investigators

• Sponsor: University of York
• Collaborators: Wellcome Trust; European and Developing Countries Clinical Trials Partnership (EDCTP); European Vaccine Initiative
• Investigators: Study Director: Paul M Kaye, PhD, University of York

Study record dates

Study Major Dates

• Study Start (Anticipated): October 1, 2023
• Primary Completion (Anticipated): December 1, 2024
• Study Completion (Anticipated): July 1, 2025

Study Registration Dates

• First Submitted: September 23, 2019
• First Submitted That Met QC Criteria: September 25, 2019
• First Posted (Actual): September 27, 2019

Study Record Updates

• Last Update Posted (Actual): September 30, 2022
• Last Update Submitted That Met QC Criteria: September 29, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Infections; Vector Borne Diseases; Parasitic Diseases; Protozoan Infections; Skin Diseases, Parasitic; Skin Diseases, Infectious; Euglenozoa Infections; Leishmaniasis; Leishmaniasis, Visceral
• Other Study ID Numbers: LEISH3 (RIA2016V-1640)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No