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

NCT ID: NCT04107961

Last Updated: 2022-09-30

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-10-01
• Study Completion Date: 2025-07-31

Brief Summary

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

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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Conditions

Post-kala-azar Dermal Leishmaniasis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: TRIPLE

Study Groups

Vaccine arm

Vaccine in 1 ml, single dose

Group Type: EXPERIMENTAL

Vaccine

Intervention Type: BIOLOGICAL

Single intramuscular injection into the deltoid region

Placebo

1 ml normal saline , single dose

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Single intramuscular injection into the deltoid region

Interventions

Vaccine

Single intramuscular injection into the deltoid region

Intervention Type: BIOLOGICAL

Placebo

Single intramuscular injection into the deltoid region

Intervention Type: OTHER

Other Intervention Names

ChAd63-KH

Eligibility Criteria

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.

• 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

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)

• Minimum Eligible Age: 12 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Wellcome Trust

OTHER

Sponsor Role: collaborator

European and Developing Countries Clinical Trials Partnership (EDCTP)

OTHER_GOV

Sponsor Role: collaborator

European Vaccine Initiative

OTHER

Sponsor Role: collaborator

University of York

OTHER

Sponsor Role: lead

Responsible Party

Paul Kaye

Project Lead

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Paul M Kaye, PhD

Role: STUDY_DIRECTOR

University of York

Other Identifiers

LEISH3 (RIA2016V-1640)

Identifier Type: -

Identifier Source: org_study_id