Visceral LeishmaniasisPhase 2NCT01980199
Trial to Determine Efficacy of Fexinidazole in Visceral Leihmaniasis Patients in Sudan
A Phase 2 study testing Fexinidazole in people with Visceral Leishmaniasis, run by Drugs for Neglected Diseases at 1 site in Sudan.
Trial summary
This study is designed to determine the efficacy of Fexinidazole as an oral treatment in Visceral Leishmanisasis sudanese adults patients. The results of this proof of concept study will allow to make a decision on whether to proceed with clinical development of Fexinidazole for visceral leishmaniasis. Read more about this study
- Who is it for?
- Ages 15 to 60 years
- Conditions the study is for
- Visceral Leishmaniasis
- What is being tested?
- Fexinidazole
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 1 siteSudan
- Study dates
- Nov 2013to Sep 2015
- 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 15 to 60 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Patients with clinical signs and symptoms of primary VL (fever for at least 2 weeks, splenomegaly) and diagnosis confirmed by visualization of parasites in tissue samples (lymph node, bone marrow) on microscopy.
- Patients aged between 15 and 60 years (inclusive) who are able to comply with the protocol.
- Patients for whom written informed consent has been signed by the patients themselves (if aged 18 years and over) or by parents(s) or legal guardian for patients under 18 years of age together with the patients assent.
- HIV negative status
Who cannot join
- Patients who have previously been diagnosed with VL and received anti-leishmanial treatment (ie relapse)
- Patients with BMI <16 kg/m2
- Patients with contra-indication (known hypersensitivity) to other imidazoles (e.g. ketaconazole)
- Patients suffering from a concomitant severe underlying disease (cardiac, renal, hepatic) including hepatitis B, para kala-azar dermal leishmaniasis and tuberculosis
- Patient with clinically significant ECG findings or QTcF≥ 450 msec in 2 successive ECGs
- Major surgical intervention 4 weeks prior to enrollment.
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- Patients who are pregnant or lactating.
- Female patients of child bearing age who do not agree to use an acceptable method of contraception
- Patients with haemoglobin < 5g/dl.
- Patients with platelets < 40,000/mm³.
- Patients with liver function (ALT and AST) tests of more than 2 times the upper limit of the normal range.
- Patients with serum creatinine above the normal range for age and gender.
- Patients with serum potassium (K+) above the normal range
- Patients with Bilirubin more than 1.5 times the upper limit of the normal range
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase II Proof of Concept Trial to Determine Efficacy of Fexinidazole in Visceral Leishmaniasis Patients in Sudan
This study is designed to determine the efficacy of Fexinidazole as an oral treatment in Visceral Leishmanisasis sudanese adults patients.
The results of this proof of concept study will allow to make a decision on whether to proceed with clinical development of Fexinidazole for visceral leishmaniasis.
Read the detailed description
Visceral Leishmaniasis (VL) is a neglected disease and it is fatal if left untreated.
Until recently the first line treatment in East Africa was 30 days of Sodium Stibogluconate which can be cardiotoxic. Since 2010 WHO recommended Sodium Stibogluconate and Paromomycin for 17 days which is a shorter treatment but there remains the toxicity associated with these drugs. The second line treatment is Ambisome given as 6-10 intravenous infusions, whilst this has a better safety profile than other VL regimens it is expensive.
So there is an urgent need for short course oral treatment for VL particularly in the East African region.
Fexinidazole is a 2 substituted 5-nitroimidazole formulated for oral administration. Fexinidazole through its metabolites has demonstrated potent activity againts L. donovani intracellular amastigotes in vitro and in vivo in a visceral leishmaniasis mouse model.
The dose selected for this study (1800 mg/1200 mg for 4/6 days) has been based on the dose selected for a phase II trial on Human African Trypasonomiasis. It is albeit well tolerated and is one dose level below the maximum tolerated dose level established in phase I.
The trial is designed and will be analysed according to a sequential method known as the triangular test, using day 28 data. This sequential design allows for repeated interim analysis (every 10 patients). The null hypothesis is that the proportion cured is less than or equal to 75%. The primary endpoint is initial cure at day 28. The primary population for interim analyses and interim decision making will be the per protocol population.In the final analysis of cumulative patient data, Intention to Treat and Per Protocol Population analyses will be conducted.
The conventional 6 months (day 210) follow up outcome is still an important secondary endpointfor the final decision on whether to proceed with clinical development of Fexinidazole for VL.
- Conditions
- Visceral Leishmaniasis
- Being tested
- Fexinidazole
- Keywords
- visceral leishmaniasis, fexinidazole, adults, proof of concept, efficacy, safety, pharmacokinetic, pharmacodynamic
- Medical subject headings
- Leishmaniasis, Visceral
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FexinidazoleDrug
600 mg tablets given orally, after the main daily meal
- at the daily dose of 1800 mg (3 tablets) once a day for 4 days
- continued by 1200mg (2 tablets)once a day for 6 days
| Study group | Role | What they receive |
|---|---|---|
| Fexinidazole | Experimental | 600mg tablets
3 tablets once a day for 4 days continued by 2 tablets once a day for 6 days Receives: Drug: Fexinidazole |
What is being measured
The primary outcome is the main question the study is designed to answer.
Initial cure
Proportion of patients with an abscence of parasites in tissue aspirate and no rescue treatment administered up to and including day 28
Measured: Day 28
Secondary outcomes (1)
Final cure
Proportion of patients initially cured at day 28 (or day 56 for slow responders) with no further signs or symptoms of visceral leishmaniasis and no requirement for rescue medication during follow-up phase up to and including the day 210
Measured: Day 210
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Nov 2013 (estimated)
- Study startNov 2013
- Primary completionNov 2014
- Study completionSep 2015
Why it stopped: Lack of efficacy
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Visceral 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
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- Drugs for Neglected Diseases
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Ahmed M Musa, MD PhD, Principal investigator, Director, Institute of Endemic Diseases, University of Khartoum Associate Professor, Head, Department of Clinical Pathology & ImmunologyE. AG Khalil, Prof. MD, Principal investigator, Institute of Endemic Diseases (IED), University of Khartoum
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01980199
- Sponsor's protocol ID
- FEXI VL 001
- Status last verified
- Jul 2014
- First submitted
- 4 Nov 2013
- Last updated
- 30 Oct 2015
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Oct 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Proof of Concept Trial to Determine Efficacy of Fexinidazole in Visceral Leishmaniasis Patients in Sudan
- ClinicalTrials.gov ID
- NCT01980199
- Acronym / sponsor ID
- FEXI VL 001
- Conditions
- Visceral Leishmaniasis
- Keywords
- visceral leishmaniasis, fexinidazole, adults, proof of concept, efficacy, safety, pharmacokinetic, pharmacodynamic
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Lack of efficacy
- Enrolment
- 14 participants (actual)
- Lead sponsor
- Drugs for Neglected DiseasesUniversity, hospital or other
- Study start
- Nov 2013
- Primary completion
- Nov 2014 (actual)
- Study completion
- Sep 2015 (actual)
- First posted
- 8 Nov 2013 (estimated)
- 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.
This study is designed to determine the efficacy of Fexinidazole as an oral treatment in Visceral Leishmanisasis sudanese adults patients.
The results of this proof of concept study will allow to make a decision on whether to proceed with clinical development of Fexinidazole for visceral leishmaniasis.
Detailed description
Visceral Leishmaniasis (VL) is a neglected disease and it is fatal if left untreated.
Until recently the first line treatment in East Africa was 30 days of Sodium Stibogluconate which can be cardiotoxic. Since 2010 WHO recommended Sodium Stibogluconate and Paromomycin for 17 days which is a shorter treatment but there remains the toxicity associated with these drugs. The second line treatment is Ambisome given as 6-10 intravenous infusions, whilst this has a better safety profile than other VL regimens it is expensive.
So there is an urgent need for short course oral treatment for VL particularly in the East African region.
Fexinidazole is a 2 substituted 5-nitroimidazole formulated for oral administration. Fexinidazole through its metabolites has demonstrated potent activity againts L. donovani intracellular amastigotes in vitro and in vivo in a visceral leishmaniasis mouse model.
The dose selected for this study (1800 mg/1200 mg for 4/6 days) has been based on the dose selected for a phase II trial on Human African Trypasonomiasis. It is albeit well tolerated and is one dose level below the maximum tolerated dose level established in phase I.
The trial is designed and will be analysed according to a sequential method known as the triangular test, using day 28 data. This sequential design allows for repeated interim analysis (every 10 patients). The null hypothesis is that the proportion cured is less than or equal to 75%. The primary endpoint is initial cure at day 28. The primary population for interim analyses and interim decision making will be the per protocol population.In the final analysis of cumulative patient data, Intention to Treat and Per Protocol Population analyses will be conducted.
The conventional 6 months (day 210) follow up outcome is still an important secondary endpointfor the final decision on whether to proceed with clinical development of Fexinidazole for VL.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Fexinidazole | Experimental | Drug: Fexinidazole600mg tablets 3 tablets once a day for 4 days continued by 2 tablets once a day for 6 days |
Who may qualify
- Ages
- 15 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (4 listed)
- Patients with clinical signs and symptoms of primary VL (fever for at least 2 weeks, splenomegaly) and diagnosis confirmed by visualization of parasites in tissue samples (lymph node, bone marrow) on microscopy.
- Patients aged between 15 and 60 years (inclusive) who are able to comply with the protocol.
- Patients for whom written informed consent has been signed by the patients themselves (if aged 18 years and over) or by parents(s) or legal guardian for patients under 18 years of age together with the patients assent.
- HIV negative status
Key exclusion criteria (14 listed)
- Patients who have previously been diagnosed with VL and received anti-leishmanial treatment (ie relapse)
- Patients with BMI <16 kg/m2
- Patients with contra-indication (known hypersensitivity) to other imidazoles (e.g. ketaconazole)
- Patients suffering from a concomitant severe underlying disease (cardiac, renal, hepatic) including hepatitis B, para kala-azar dermal leishmaniasis and tuberculosis
- Patient with clinically significant ECG findings or QTcF≥ 450 msec in 2 successive ECGs
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 |
|---|---|---|
| Fexinidazole600 mg tablets given orally, after the main daily meal * at the daily dose of 1800 mg (3 tablets) once a day for 4 days * continued by 1200mg (2 tablets)once a day for 6 days | Drug | Fexinidazole |
Primary outcome
Initial cure
Time frame: Day 28
Proportion of patients with an abscence of parasites in tissue aspirate and no rescue treatment administered up to and including day 28
1 secondary outcome
Final cure
Time frame: Day 210
Results and safety
The study was stopped early (reason given: Lack of efficacy). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Oct 2015.
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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.
Ahmed M Musa, MD PhD principal investigator
Director, Institute of Endemic Diseases, University of Khartoum Associate Professor, Head, Department of Clinical Pathology & Immunology
E. AG Khalil, Prof. MD principal investigator
Institute of Endemic Diseases (IED), University of Khartoum
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Fexinidazole in people with Visceral Leishmaniasis, run by Drugs for Neglected Diseases at 1 site in Sudan.
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 4 inclusion and 14 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: stopped early, as of the sponsor's last update on 30 Oct 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Sudan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. 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 stopped early (reason given: Lack of efficacy). Results are not available in the source record.
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?
Initial cure (time frame: Day 28). 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 Oct 2015.