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

NCT ID: NCT03969134

Last Updated: 2023-05-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 86 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-04-06
• Study Completion Date: 2023-02-28

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:

1. To compare the humoral and cellular immune responses generated by the candidate vaccine in patients with persistent PKDL.

2. To observe any clinical changes in the cutaneous PKDL disease over a 120 day period following vaccination

Conditions

Leishmaniasis, Cutaneous

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Vaccine arm

ChAd63 KH 7.5x1010 vp, single dose, by IM injection

Group Type: ACTIVE_COMPARATOR

ChAd63-KH

Intervention Type: BIOLOGICAL

The vaccine will be injected intramuscularly into the arm.

Placebo

Normal Saline, single dose, by IM injection

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

The placebo will be injected intramuscularly into the arm.

Interventions

ChAd63-KH

The vaccine will be injected intramuscularly into the arm.

Intervention Type: BIOLOGICAL

Placebo

The placebo will be injected intramuscularly into the arm.

Intervention Type: OTHER

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

• Minimum Eligible Age: 12 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of York

OTHER

Sponsor Role: lead

Responsible Party

Paul Kaye

Project Lead

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Institute of Tropical Medicine

Doka, Gedarif, Sudan

Countries

Sudan

References

Younis BM, Wiggins R, Khalil EAG, Osman M, Santoro F, Sonnati C, Keding A, Novedrati M, Montesi G, Noureldein A, Elmukashfi ETA, Mustafa AE, Alamin M, Saeed M, Salman K, Suliman AJ, Musa AEA, Layton AM, Lacey CJN, Kaye PM, Musa AM. A randomized, double-blind phase 2b trial to evaluate efficacy of ChAd63-KH for treatment of post kala-azar dermal leishmaniasis. Mol Ther Methods Clin Dev. 2024 Jul 30;32(3):101310. doi: 10.1016/j.omtm.2024.101310. eCollection 2024 Sep 12.

Reference Type: DERIVED

PMID: 39253357 (View on PubMed)

Lacey C, Musa A, Khalil ET, Younis B, Osman M, Wiggins R, Keding A, Kaye P. LEISH2b - A phase 2b study to assess the safety, efficacy, and immunogenicity of the Leishmania vaccine ChAd63-KH in post-kala azar dermal leishmaniasis. Wellcome Open Res. 2022 Aug 3;7:200. doi: 10.12688/wellcomeopenres.17951.1. eCollection 2022.

Reference Type: DERIVED

PMID: 37252616 (View on PubMed)

Other Identifiers

LEISH2b

Identifier Type: -

Identifier Source: org_study_id