A Study of a New Leishmania Vaccine Candidate ChAd63-KH (Leish2a)
Primary Purpose
Leishmaniasis, Cutaneous
Status
Completed
Phase
Phase 2
Locations
Sudan
Study Type
Interventional
Intervention
ChAd63-KH
Sponsored by
About this trial
This is an interventional treatment trial for Leishmaniasis, Cutaneous
Eligibility Criteria
Inclusion Criteria:
- Adults
The volunteer must be:
- Aged 18 to 50 years on the day of screening
- Females must be unmarried, single, or widowed
- Willing and able to give written informed consent
Adolescents
- Aged 12 to 17 years on the day of screening
- Female adolescents must be unmarried
- Written informed consent must be obtained from a parent
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
- 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
- Is negative for antibodies in the RK39 strip test
- 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
- 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
- Centre for Tropical Medicine
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
ChAd63- KH
ChAd63-KH
Arm Description
Single intramuscular dose of ChAd63-KH, 1 x10(10)vp or, following safety review, 7.5 x 10(10)vp in adults
Single intramuscular dose of ChAd63-KH, 1x10(10)vp or, following safety review, 7.5 x 10(10)vp in adolescents
Outcomes
Primary Outcome Measures
Safety
Safety of a new candidate Leishmania vaccine in patients with persistent PKDL, assessed by the occurrence of biochemical, haematological and physiological responses which meet the criteria for adverse events/serious adverse events as described in the clinical trial protocol (v1.55)
Secondary Outcome Measures
Cellular immune responses
To compare the humoral and cellular immune responses generated by the candidate vaccine in patients with persistent PKDL.
Clinical changes in cutaneous PKDL disease
To observe any clinical changes in the cutaneous PKDL disease over a 42 day period according to a clinical grading score following vaccination
Full Information
NCT ID
NCT02894008
First Posted
August 1, 2016
Last Updated
January 27, 2020
Sponsor
University of York
Collaborators
University of Khartoum
1. Study Identification
Unique Protocol Identification Number
NCT02894008
Brief Title
A Study of a New Leishmania Vaccine Candidate ChAd63-KH
Acronym
Leish2a
Official Title
A Phase IIa Safety Study to Assess the Safety and Immunogenicity of a New Leishmania Vaccine Candidate ChAd63-KH
Study Type
Interventional
2. Study Status
Record Verification Date
January 2020
Overall Recruitment Status
Completed
Study Start Date
November 2016 (Actual)
Primary Completion Date
September 30, 2019 (Actual)
Study Completion Date
December 31, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of York
Collaborators
University of Khartoum
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This is a study to assess the safety of a new candidate Leishmania vaccine ChAd63-KH in patients with persistent post kala azar dermal leishmaniasis (PKDL).
This is a Phase II trial in patients with PKDL, to assess the safety and compare the humoral and cellular immune responses generated by the candidate vaccine in patients, and observe any clinical changes in the disease over a 42 day period following vaccination.
Study design: Eight adult volunteers will receive 1x10(10)vp and the subsequent eight volunteers will receive 7.5 x10(10)vp. Adolescents will be vaccinated with either 1x10(10)vp or 7.5 x10(10)vp, to be determined by evaluation of all available data after DSMB & CTSC review.
Detailed Description
This is a study to assess the safety of a new candidate Leishmania vaccine ChAd63-KH in patients with persistent post kala azar dermal leishmaniasis (PKDL). With 95% of cases occurring in India, Bangladesh, Nepal, the Sudan and Brazil, visceral leishmaniasis (VL) is a disease of the poor. With an estimated 40,000 or more deaths annually, mostly children and young adults, VL ranks second only to malaria amongst parasitic infections for mortality, and as measured by DALYs lost, it ranks in the top ten infectious diseases globally. No effective vaccine has yet been developed for VL / PKDL despite significant research efforts.
The investigators have recently completed a successful first-in-human clinical trial of a new therapeutic vaccine for VL / PKDL (ChAd63-KH). This trial demonstrated safety of ChAd63-KH in healthy UK adult volunteers and immunogenicity against the two Leishmania antigens on par with that seen to other vaccine candidate antigens in clinical development for other diseases (e.g. malaria, HCV, Ebola). Following external peer review of the data generated during LEISH1, the investigators have been awarded further Wellcome Trust funding to progress this vaccine into Phase II clinical trials in patients with PKDL.
Study design: The first eight adult volunteers will receive 1x10(10)vp and, following DSMB and CTSC review, the subsequent eights adult volunteers will receive 7.5 x10(10)vp. Doses will be administered at a single time point. Adolescents will be vaccinated with either 1x10(10)vp or 7.5 x10(10)vp, to be determined by evaluation of all available data after DSMB & CTSC review.
Objectives:
To assess the safety of a new candidate Leishmania vaccine ChAd63- KH in patients with persistent PKDL.
Secondary objectives:
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 42 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
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
24 (Actual)
8. Arms, Groups, and Interventions
Arm Title
ChAd63- KH
Arm Type
Experimental
Arm Description
Single intramuscular dose of ChAd63-KH, 1 x10(10)vp or, following safety review, 7.5 x 10(10)vp in adults
Arm Title
ChAd63-KH
Arm Type
Experimental
Arm Description
Single intramuscular dose of ChAd63-KH, 1x10(10)vp or, following safety review, 7.5 x 10(10)vp in adolescents
Intervention Type
Drug
Intervention Name(s)
ChAd63-KH
Intervention Description
ChAd63-KH in adults and adolescents with persistent PKDL.
Primary Outcome Measure Information:
Title
Safety
Description
Safety of a new candidate Leishmania vaccine in patients with persistent PKDL, assessed by the occurrence of biochemical, haematological and physiological responses which meet the criteria for adverse events/serious adverse events as described in the clinical trial protocol (v1.55)
Time Frame
90 days
Secondary Outcome Measure Information:
Title
Cellular immune responses
Description
To compare the humoral and cellular immune responses generated by the candidate vaccine in patients with persistent PKDL.
Time Frame
90 days
Title
Clinical changes in cutaneous PKDL disease
Description
To observe any clinical changes in the cutaneous PKDL disease over a 42 day period according to a clinical grading score following vaccination
Time Frame
42 days following vaccination
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:
Adults
The volunteer must be:
Aged 18 to 50 years on the day of screening
Females must be unmarried, single, or widowed
Willing and able to give written informed consent
Adolescents
Aged 12 to 17 years on the day of screening
Female adolescents must be unmarried
Written informed consent must be obtained from a parent
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
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
Is negative for antibodies in the RK39 strip test
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
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ahmed Musa, MBBS
Organizational Affiliation
University of Khartoum
Official's Role
Principal Investigator
Facility Information:
Facility Name
Centre for Tropical Medicine
City
Doka
State/Province
Gedarif
Country
Sudan
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Citations:
PubMed Identifier
33781913
Citation
Younis BM, Osman M, Khalil EAG, Santoro F, Furini S, Wiggins R, Keding A, Carraro M, Musa AEA, Abdarahaman MAA, Mandefield L, Bland M, Aebischer T, Gabe R, Layton AM, Lacey CJN, Kaye PM, Musa AM. Safety and immunogenicity of ChAd63-KH vaccine in post-kala-azar dermal leishmaniasis patients in Sudan. Mol Ther. 2021 Jul 7;29(7):2366-2377. doi: 10.1016/j.ymthe.2021.03.020. Epub 2021 Mar 27.
Results Reference
derived
Learn more about this trial
A Study of a New Leishmania Vaccine Candidate ChAd63-KH
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