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

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ClinicalTrials.gov Identifier: NCT04107961
Recruitment Status : Not yet recruiting
First Posted : September 27, 2019
Last Update Posted : July 31, 2020
Sponsor:
Collaborators:
Wellcome Trust
EDCTP
European Vaccine Initiative
Information provided by (Responsible Party):
Paul Kaye, University of York

Brief Summary:
The LEISH3 trial is a randomised, controlled, double blind Phase II clinical trial to evaluate the safety and efficacy of vaccination with ChAd63-KH in the prevention of post-kala azar dermal leishmaniasis (PKDL) in Sudanese visceral leishmaniasis (VL) patients previously treated with sodium stibogluconate / paromomycin (SSG / PM).

Condition or disease Intervention/treatment Phase
Post-kala-azar Dermal Leishmaniasis Biological: Vaccine Other: Placebo Phase 2

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.

The format of the LEISH3 trial is randomised, controlled, double blind Phase II clinical trial.

The primary objective is to evaluate the safety and efficacy of vaccination with ChAd63-KH in the prevention of post-kala azar dermal leishmaniasis (PKDL) in 262 Sudanese visceral leishmaniasis (VL) patients aged between 12 and 50 years who have been previously treated with sodium stibogluconate / paromomycin (SSG / PM). Follow up is 12 months from vaccination. The secondary objectives are:

  1. To compare systemic immune responses in vaccine vs placebo arms.
  2. In all subjects, after treatment of VL, to measure skin Leishmania parasite load and multi-parameter immune phenotypes as predictors of PKDL development and in relation to receipt of vaccine or placebo
  3. In subjects developing PKDL within the trial, to delineate the pathogenesis of PKDL by comparing skin Leishmania parasite load and multi-parameter immune phenotypes pre-vaccination and at PKDL onset, and in relation to receipt of vaccine or placebo.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 262 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Randomised placebo-controlled double-blind study
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Masking Description: Double blinded placebo controlled
Primary Purpose: Prevention
Official Title: 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
Estimated Study Start Date : October 1, 2020
Estimated Primary Completion Date : December 2023
Estimated Study Completion Date : July 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Leishmaniasis

Arm Intervention/treatment
Experimental: Vaccine arm
Vaccine in 1 ml, single dose
Biological: Vaccine
Single intramuscular injection into the deltoid region
Other Name: ChAd63-KH

Placebo Comparator: Placebo
1 ml normal saline , single dose
Other: Placebo
Single intramuscular injection into the deltoid region




Primary Outcome Measures :
  1. Safety of single dose vaccination with ChAd63-KH [ Time Frame: 12 months from vaccination ]
    Treatment-related adverse events as defined in the clinical trial protocol (median no. events)

  2. Efficacy of single dose vaccination with ChAd63-KH [ Time Frame: 12 months from vaccination ]
    Frequency of occurrence of PKDL in patients completing treatment with SSG / PM.


Secondary Outcome Measures :
  1. Immunological response: T cells [ Time Frame: 12 months from vaccination ]
    To compare systemic immune responses in vaccine vs placebo arms by measurement of the frequency (median) of gamma-interferon producing T cells

  2. Immunological response: transcriptomics [ Time Frame: 12 months from vaccination ]
    Comparing transcripts for differential expression in vaccine and placebo arms

  3. Pathogenesis of PKDL comparing Leishmania parasite load pre-vaccination and at PKDL onset [ Time Frame: 12 months from vaccination ]
    Parasite detection using RNAscope / immunocytochemistry

  4. Immunological response: B cells [ Time Frame: 12 months from vaccination ]
    Measurement of frequency in vaccinated and placebo groups of B cells by flow cytometry

  5. Immunological response: antibody levels [ Time Frame: 12 months from vaccination ]
    To compare systemic immune responses in vaccine vs placebo arms by median optical density levels



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   12 Years to 50 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04107961


Contacts
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Contact: Rebecca C Wiggins, PhD 0044190432 ext 8934 rebecca.wiggins@york.ac.uk
Contact: Charles Lacey, MD 00441904 ext 8879 charles.lacey@hyms.ac.uk

Sponsors and Collaborators
University of York
Wellcome Trust
EDCTP
European Vaccine Initiative
Investigators
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Study Director: Paul M Kaye, PhD University of York
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Responsible Party: Paul Kaye, Project Lead, University of York
ClinicalTrials.gov Identifier: NCT04107961    
Other Study ID Numbers: LEISH3 (RIA2016V-1640)
First Posted: September 27, 2019    Key Record Dates
Last Update Posted: July 31, 2020
Last Verified: July 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Leishmaniasis
Leishmaniasis, Visceral
Euglenozoa Infections
Protozoan Infections
Parasitic Diseases
Skin Diseases, Parasitic
Skin Diseases, Infectious
Skin Diseases