A Study to Assess Safety and Efficacy of a Leishmania Vaccine to Prevent Post Kala Azar Dermal Leishmaniasis (PKDL)

NCT04107961 | Withdrawn Phase 2 DMC

• 1 other identifier: LEISH3 (RIA2016V-1640)
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

The actual format of the anticipated LEISH3 trial is under review.

Conditions

Post-kala-azar Dermal Leishmaniasis

Outcome Measures

Primary Outcomes (2)

• Safety of single dose vaccination with ChAd63-KH

  Treatment-related adverse events as defined in the clinical trial protocol (median no. events)

  12 months from vaccination

• Efficacy of single dose vaccination with ChAd63-KH

  Frequency of occurrence of PKDL in patients completing treatment with SSG / PM.

  12 months from vaccination

Secondary Outcomes (5)

• Immunological response: T cells

  12 months from vaccination

• Immunological response: transcriptomics

  12 months from vaccination

• Pathogenesis of PKDL comparing Leishmania parasite load pre-vaccination and at PKDL onset

  12 months from vaccination

• Immunological response: B cells

  12 months from vaccination

• Immunological response: antibody levels

  12 months from vaccination

Study Arms (2)

Vaccine arm

EXPERIMENTAL

Vaccine in 1 ml, single dose

Biological: Vaccine

Placebo

PLACEBO COMPARATOR

1 ml normal saline , single dose

Other: Placebo

Interventions

Vaccine BIOLOGICAL

Single intramuscular injection into the deltoid region

Also known as: ChAd63-KH

Vaccine arm

Placebo OTHER

Single intramuscular injection into the deltoid region

Placebo

Eligibility Criteria

• Age: 12 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• The patient volunteer must be:
• Aged 12 to 50 years on the day of screening
• Have had VL and have been cured following a standard regimen of SSG / PM
• 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.
• All Participants
• Uncomplicated VL responsive to SSG / PM treatment
• Have relatively normal blood values in the setting of VL, defined as hemoglobin \>5.0 g/dL, white blood cells \>1.0 x10(9)/L, platelets \>40 x10(9)/L, liver function tests \< x5 normal, Creatinine \<1.5 mg/dL
• Available for the duration of the study
• Without any other significant health problems 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
• Negative for human immunodeficiency virus (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 3, 6, 9 and 12 months after vaccination.

You may not qualify if:

• The volunteer may not enter the study if any of the following apply:
• Has HIV/VL coinfection
• Has had previous treatment for VL with relapse
• 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 hepatitis C virus)
• 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

Sponsors & Collaborators

• University of York: lead
• Wellcome Trust: collaborator
• European and Developing Countries Clinical Trials Partnership (EDCTP): collaborator
• European Vaccine Initiative: collaborator

MeSH Terms

Interventions

Vaccines

Intervention Hierarchy (Ancestors)

Biological Products; Complex Mixtures

Study Officials

• Paul M Kaye, PhD

  University of York

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double blinded placebo controlled
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Project Lead

Model Details: Randomised placebo-controlled double-blind study

Study Record Dates

• First Submitted: September 23, 2019
• First Posted: September 27, 2019
• Study Start: October 1, 2023
• Primary Completion: December 1, 2024
• Study Completion: July 1, 2025
• Last Updated: September 30, 2022

Record last verified: 2022-09

Data Sharing

• IPD Sharing: Will not share