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

University of York

Status and phase

Completed

Phase 2

Conditions

Leishmaniasis, Cutaneous

Treatments

Biological: ChAd63-KH

Other: Placebo

Study type

Interventional

Funder types

Other

Identifiers

NCT03969134

LEISH2b

Details and patient eligibility

About

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.

Full 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

Enrollment

86 patients

Sex

All

Ages

12 to 50 years old

Volunteers

No Healthy Volunteers

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