A Study to Assess the Safety, Efficacy and Immunogenicity of Leishmania Vaccine ChAd63-KH in PKDL

Study Overview
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Brief Summary
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This trial is designed to assess the therapeutic efficacy and safety of CHAd63-KH, a new candidate Leishmania vaccine, in patients with persistent PKDL. 100 participants will be randomly assigned (50 participants in each arm) to receive placebo or ChAd63-KH 7.5 x10(10)vp. Doses will be administered at a single time point.

Detailed Description
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This study is a randomised, double blinded, placebo controlled trial designed to assess the therapeutic efficacy and safety of CHAd63-KH, a new candidate Leishmania vaccine, in patients with persistent PKDL. 100 participants will be randomly assigned (50 participants in each arm) to receive placebo or ChAd63-KH 7.5 x10(10)vp intramuscular injection into the deltoid region. Doses will be administered at a single time point. Volunteers aged between 12-50 years with persistent PKDL will be recruited at Professor El-Hassan's Centre for Tropical Medicine, Dooka, Gedarif State, Sudan, and will be followed up for 120 days after the dosing visit. The trial is planned to run for 24 months. Secondary objectives are as follows: To compare the humoral and cellular immune responses generated by the candidate vaccine in patients with persistent PKDL. To observe any clinical changes in the cutaneous PKDL disease over a 120 day period following vaccination

Official Title
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A Phase IIb Study to Assess the Safety, Efficacy and Immunogenicity of the Leishmania Vaccine ChAd63-KH in Post-kala Azar Dermal Leishmaniasis

Conditions
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Leishmaniasis, Cutaneous

Intervention / Treatment
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* Biological: ChAd63-KH
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The volunteer must be: Aged 12 to 50 years on the day of screening 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 and assent from them. All Participants Uncomplicated PKDL of > 6 month's duration Available for the duration of the study In otherwise good health 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 Willing to undergo screening for HIV, Hepatitis B and Hepatitis C Leishmania PCR positive on the screening skin biopsy For females only, willing to undergo urinary pregnancy tests on the day of screening, on the day of vaccination (prior to vaccination) and 7 and 42 days after vaccination. Exclusion Criteria: The volunteer may not enter the study if any of the following apply: Has mucosal or conjunctival PKDL Has had treatment for PKDL within 21 days 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 HCV) Any clinically significant abnormal finding on screening 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

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomised, double blinded, placebo controlled
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Vaccine arm<br>ChAd63 KH 7.5x1010 vp, single dose, by IM injection | Biological: ChAd63-KH<br>* The vaccine will be injected intramuscularly into the arm.<br>|
| Placebo Comparator: Placebo<br>Normal Saline, single dose, by IM injection | Other: Placebo<br>* The placebo will be injected intramuscularly into the arm.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the number of participants with treatment-related adverse events as defined in the clinical trial protocol V1.0. | To assess the number of participants with treatment-related adverse events as defined in the clinical trial protocol V1.0. | 24 months | 
| To assess the therapeutic efficacy of CHAd63-KH, a new candidate, in patients with PKDL by clinical judgement of PKDL lesion reduction. | To assess the therapeutic efficacy of CHAd63-KH, a new candidate, in patients with PKDL by clinical judgement of PKDL lesion reduction. | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immune responses by presence of interferon gamma producing T cells | To identify cellular immune responses generated by the candidate vaccine in patients with persistent PKDL using a gamma interferon ELISpot assay | 24 months | 
| Immune responses by presence of serum antibodies against Leishmania peptides | To identify humoral immune responses generated by the candidate vaccine in patients with persistent PKDL using a gamma interferon ELISpot assay | 24 months | 
| Clinical changes in PKDL disease | To observe any changes in the appearance of the cutaneous PKDL disease over a 120 day period following vaccination. | 24 months |