A Study to Assess the Safety, Efficacy and Immunogenicity of Leishmania Vaccine ChAd63-KH in PKDL
Primary Purpose
Leishmaniasis, Cutaneous
Status
Completed
Phase
Phase 2
Locations
Sudan
Study Type
Interventional
Intervention
ChAd63-KH
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Leishmaniasis, Cutaneous
Eligibility Criteria
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
Sites / Locations
- Institute of Tropical Medicine
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
Vaccine arm
Placebo
Arm Description
ChAd63 KH 7.5x1010 vp, single dose, by IM injection
Normal Saline, single dose, by IM injection
Outcomes
Primary Outcome Measures
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.
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.
Secondary Outcome Measures
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
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
Clinical changes in PKDL disease
To observe any changes in the appearance of the cutaneous PKDL disease over a 120 day period following vaccination.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03969134
Brief Title
A Study to Assess the Safety, Efficacy and Immunogenicity of Leishmania Vaccine ChAd63-KH in PKDL
Official Title
A Phase IIb Study to Assess the Safety, Efficacy and Immunogenicity of the Leishmania Vaccine ChAd63-KH in Post-kala Azar Dermal Leishmaniasis
Study Type
Interventional
2. Study Status
Record Verification Date
May 2023
Overall Recruitment Status
Completed
Study Start Date
April 6, 2020 (Actual)
Primary Completion Date
August 31, 2022 (Actual)
Study Completion Date
February 28, 2023 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of York
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Leishmaniasis, Cutaneous
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Randomised, double blinded, placebo controlled
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Fifty volunteers receive a single intramuscular dose of ChAd63 KH 7.5x1010vp and 50 placebo. Investigators and the participant will be blinded. A pharmacist and nurse will prepare the injections. There will be stratification between patients aged 12-17, and patients aged 18-50, to ensure balanced randomisation. The pharmacist will be told which age strata the patient is in by a nurse, and will prepare the injection with the study nurse. There will be two series of sealed envelopes, one for each of the adolescent and adult cohorts. These envelopes will have external labelling, with the cohort, and successive cohort patient numbering. Each envelope contains randomisation to VACCINE or SALINE. The vaccine and placebo injections will be prepared in blacked-out syringes labelled with patient cohort number. The study nurse will take the prepared injection to the clinical team for administration. The syringe will be further labelled with the patient's initials, date and time of injection.
Allocation
Randomized
Enrollment
86 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Vaccine arm
Arm Type
Active Comparator
Arm Description
ChAd63 KH 7.5x1010 vp, single dose, by IM injection
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Normal Saline, single dose, by IM injection
Intervention Type
Biological
Intervention Name(s)
ChAd63-KH
Intervention Description
The vaccine will be injected intramuscularly into the arm.
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
The placebo will be injected intramuscularly into the arm.
Primary Outcome Measure Information:
Title
To assess the number of participants with treatment-related adverse events as defined in the clinical trial protocol V1.0.
Description
To assess the number of participants with treatment-related adverse events as defined in the clinical trial protocol V1.0.
Time Frame
24 months
Title
To assess the therapeutic efficacy of CHAd63-KH, a new candidate, in patients with PKDL by clinical judgement of PKDL lesion reduction.
Description
To assess the therapeutic efficacy of CHAd63-KH, a new candidate, in patients with PKDL by clinical judgement of PKDL lesion reduction.
Time Frame
24 months
Secondary Outcome Measure Information:
Title
Immune responses by presence of interferon gamma producing T cells
Description
To identify cellular immune responses generated by the candidate vaccine in patients with persistent PKDL using a gamma interferon ELISpot assay
Time Frame
24 months
Title
Immune responses by presence of serum antibodies against Leishmania peptides
Description
To identify humoral immune responses generated by the candidate vaccine in patients with persistent PKDL using a gamma interferon ELISpot assay
Time Frame
24 months
Title
Clinical changes in PKDL disease
Description
To observe any changes in the appearance of the cutaneous PKDL disease over a 120 day period following vaccination.
Time Frame
24 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
12 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Facility Information:
Facility Name
Institute of Tropical Medicine
City
Doka
State/Province
Gedarif
Country
Sudan
12. IPD Sharing Statement
Plan to Share IPD
No
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A Study to Assess the Safety, Efficacy and Immunogenicity of Leishmania Vaccine ChAd63-KH in PKDL
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