Post-kala-azar Dermal LeishmaniasisPhase 2LEISH3NCT04107961
A Study to Assess Safety and Efficacy of a Leishmania Vaccine to Prevent Post Kala Azar Dermal Leishmaniasis (PKDL)
A Phase 2 study testing Vaccine in people with Post-kala-azar Dermal Leishmaniasis, run by University of York.
Trial summary
The actual format of the anticipated LEISH3 trial is under review. Read more about this study
- Who is it for?
- Ages 12 to 50 years
- Conditions the study is for
- Post-kala-azar Dermal Leishmaniasis
- What is being tested?
- Vaccine
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 1 Oct 2023to Jul 2025
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 to 50 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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.
Show all 15Show fewer
- 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.
Who cannot join
- 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
Show all 16Show fewer
- 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)
- Significant abnormal finding (in the setting of VL, see definitions in Inclusion criteria) on entry 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
About this study
Official title: A Phase II Study to Assess the Safety and Efficacy of the Leishmania Vaccine ChAd63-KH for the Prevention of Post-kala Azar Dermal Leishmaniasis
The actual format of the anticipated LEISH3 trial is under review.
Read the detailed description
The leishmaniases are poverty-related neglected diseases with a major impact on health worldwide. They affect the poorest of the poor and present a severe barrier to socio-economic development. Caused by infection with one of several species of Leishmania parasite, these diseases occur in 98 countries worldwide and can be broadly classified as tegumentary leishmaniases (TL; affecting the skin and mucosa) and visceral leishmaniasis (VL; affecting internal organs). Worldwide, over 1 million reported cases of TL and 0.5 million reported cases of VL occur each year. Whereas TL are chronic and non-life-threatening, VL is responsible for over 20,000 deaths per year, second only to malaria amongst parasites with regard to mortality. Collectively, approximately 2.4 million disability-adjusted life years are lost to the leishmaniases. No vaccines are currently licensed for any form of human leishmaniasis and the drug arsenal is limited and increasingly compromised by drug resistance.
.
- Conditions
- Post-kala-azar Dermal Leishmaniasis
- Being tested
- Vaccine, Placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VaccineBiological
Also called ChAd63-KH
Single intramuscular injection into the deltoid region
PlaceboOther
Single intramuscular injection into the deltoid region
| Study group | Role | What they receive |
|---|---|---|
| Vaccine arm | Experimental | Vaccine in 1 ml, single dose Receives: Biological: Vaccine |
| Placebo | Placebo comparator | 1 ml normal saline , single dose Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety of single dose vaccination with ChAd63-KH
Treatment-related adverse events as defined in the clinical trial protocol (median no. events)
Measured: 12 months from vaccination
Efficacy of single dose vaccination with ChAd63-KH
Frequency of occurrence of PKDL in patients completing treatment with SSG / PM.
Measured: 12 months from vaccination
Secondary outcomes (5)
Immunological response: T cells
To compare systemic immune responses in vaccine vs placebo arms by measurement of the frequency (median) of gamma-interferon producing T cells
Measured: 12 months from vaccination
Immunological response: transcriptomics
Comparing transcripts for differential expression in vaccine and placebo arms
Measured: 12 months from vaccination
Pathogenesis of PKDL comparing Leishmania parasite load pre-vaccination and at PKDL onset
Parasite detection using RNAscope / immunocytochemistry
Measured: 12 months from vaccination
Immunological response: B cells
Measurement of frequency in vaccinated and placebo groups of B cells by flow cytometry
Measured: 12 months from vaccination
Immunological response: antibody levels
To compare systemic immune responses in vaccine vs placebo arms by median optical density levels
Measured: 12 months from vaccination
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Sep 2019
- Study start1 Oct 2023 (estimated)
- Primary completionDec 2024 (estimated)
- Study completionJul 2025 (estimated)
Why it stopped: The trial will be undertaken but the protocol will be substantially revised.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Post-kala-azar Dermal LeishmaniasisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomised placebo-controlled double-blind study
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of York
- Sponsor type
- University, hospital or other
- Collaborators
- Wellcome Trust, European and Developing Countries Clinical Trials Partnership (EDCTP), European Vaccine Initiative
- Responsible party
- Principal investigator, Paul Kaye, University of York
- Investigators
- Paul M Kaye, PhD, Study director, University of York
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04107961
- Sponsor's protocol ID
- LEISH3 (RIA2016V-1640)
- Acronym
- LEISH3
- Status last verified
- Sep 2022
- First submitted
- 23 Sep 2019
- Last updated
- 30 Sep 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study to Assess the Safety and Efficacy of the Leishmania Vaccine ChAd63-KH for the Prevention of Post-kala Azar Dermal Leishmaniasis
- ClinicalTrials.gov ID
- NCT04107961
- Acronym / sponsor ID
- LEISH3 / LEISH3 (RIA2016V-1640)
- Conditions
- Post-kala-azar Dermal Leishmaniasis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: The trial will be undertaken but the protocol will be substantially revised.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of YorkUniversity, hospital or other
- Collaborators
- Wellcome Trust, European and Developing Countries Clinical Trials Partnership (EDCTP), European Vaccine Initiative
- Study start
- 1 Oct 2023 (estimated)
- Primary completion
- Dec 2024 (estimated)
- Study completion
- Jul 2025 (estimated)
- First posted
- 27 Sep 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The actual format of the anticipated LEISH3 trial is under review.
Detailed description
The leishmaniases are poverty-related neglected diseases with a major impact on health worldwide. They affect the poorest of the poor and present a severe barrier to socio-economic development. Caused by infection with one of several species of Leishmania parasite, these diseases occur in 98 countries worldwide and can be broadly classified as tegumentary leishmaniases (TL; affecting the skin and mucosa) and visceral leishmaniasis (VL; affecting internal organs). Worldwide, over 1 million reported cases of TL and 0.5 million reported cases of VL occur each year. Whereas TL are chronic and non-life-threatening, VL is responsible for over 20,000 deaths per year, second only to malaria amongst parasites with regard to mortality. Collectively, approximately 2.4 million disability-adjusted life years are lost to the leishmaniases. No vaccines are currently licensed for any form of human leishmaniasis and the drug arsenal is limited and increasingly compromised by drug resistance.
.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Randomised placebo-controlled double-blind study
| Arm | Type | Receives |
|---|---|---|
| Vaccine arm | Experimental | Biological: VaccineVaccine in 1 ml, single dose |
| Placebo | Placebo comparator | Other: Placebo1 ml normal saline , single dose |
Who may qualify
- Ages
- 12 to 50 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (15 listed)
- 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.
Key exclusion criteria (16 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| VaccineAlso: ChAd63-KHSingle intramuscular injection into the deltoid region | Biological | Vaccine arm |
| PlaceboSingle intramuscular injection into the deltoid region | Other | Placebo |
Primary outcome
Safety of single dose vaccination with ChAd63-KH
Time frame: 12 months from vaccination
Treatment-related adverse events as defined in the clinical trial protocol (median no. events)
Efficacy of single dose vaccination with ChAd63-KH
Time frame: 12 months from vaccination
Frequency of occurrence of PKDL in patients completing treatment with SSG / PM.
5 secondary outcomes
Immunological response: T cells
Time frame: 12 months from vaccination
Immunological response: transcriptomics
Time frame: 12 months from vaccination
Pathogenesis of PKDL comparing Leishmania parasite load pre-vaccination and at PKDL onset
Time frame: 12 months from vaccination
Immunological response: B cells
Time frame: 12 months from vaccination
Immunological response: antibody levels
Time frame: 12 months from vaccination
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Sep 2022.
- Individual participant dataSharing planned: No
Related trials for Post-kala-azar Dermal Leishmaniasis
Not yet recruiting
Early Detection and AI-Based Management of Skin-Related Neglected Tropical Diseases in Sub-Saharan Africa by Frontline Health Workers
Skin and Connective Tissue Diseases, Neglected Tropical Diseases
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Paul M Kaye, PhD study director
University of York
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Vaccine in people with Post-kala-azar Dermal Leishmaniasis, run by University of York.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 30 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety of single dose vaccination with ChAd63-KH (time frame: 12 months from vaccination). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Sep 2022.