Trypanosomiasis, AfricanPhase 2/3NCT03974178
Fexinidazole in Human African Trypanosomiasis Due to T. b. Rhodesiense
A Phase 2/3 study testing Fexinidazole in people with Trypanosomiasis, African and Sleeping Sickness, run by Drugs for Neglected Diseases at 2 sites in 2 countries.
Trial summary
The ultimate goal of this study is to show that fexinidazole offers an alternative over the existing treatments of Human African trypanosomiasis due to Trypanosoma brucei rhodesiense (r-HAT): melarsoprol in patients with stage 2 r-HAT and suramin in patients with stage 1 r-HAT. Read more about this study
- Who is it for?
- Ages 6 years and older
- Conditions the study is for
- Trypanosomiasis, African, Sleeping Sickness, Trypanosoma Brucei Rhodesiense; Infection
- 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
- 45 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 29 Sep 2019to 12 Oct 2022
- Phase
- Phase 2/3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 6 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Signed Informed Consent Form (plus assent for children)
- ≥ 6 years old
- ≥ 20 kg body weight
- Ability to ingest at least one complete meal per day (or at least one Plumpy'Nut® sachet)
- Karnofsky index ≥ 40
- Parasitological confirmation of T. b. rhodesiense infection
- Having a permanent address or being traceable by others and willing and able to comply with follow-up visit schedule
- Agreement to be hospitalised for a minimum of 13 days and to receive the study treatment
Who cannot join
- Active clinically relevant medical conditions other than HAT that may jeopardize subject safety or at the investigator discretion may interfere with participation in the study.
- Compromised general health or severely deteriorated general condition, such as severe malnutrition, cardiovascular shock, respiratory distress, or terminal illness
- Patients with severe hepatic impairment (e.g.: clinical signs of cirrhosis or jaundice)
- Known hypersensitivity to fexinidazole, to any nitroimidazole drugs (e.g. metronidazole, tinidazole), or to any of the excipients
- Patients previously enrolled in the study or having already received fexinidazole
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
About this study
Official title: Efficacy and Safety of Fexinidazole in Patients With Human African Trypanosomiasis (HAT) Due to Trypanosoma Brucei Rhodesiense: a Multicentre, Open-label Clinical Trial
The ultimate goal of this study is to show that fexinidazole offers an alternative over the existing treatments of Human African trypanosomiasis due to Trypanosoma brucei rhodesiense (r-HAT): melarsoprol in patients with stage 2 r-HAT and suramin in patients with stage 1 r-HAT. The main questions it aims to answer are:
- Is the short-term fatality rate and failure rate associated with fexinidazole lower than those of melarsoprol in patients with stage 2 r-HAT?
- Is the long-term failure rate associated with fexinidazole lower than that of melarsoprol in patients with stage 2 r-HAT?
- Can fexinidazole in patients with stage 1 r-HAT replace the treatment with suramin?
- Is fexinidazole treatment safe in patient with r-HAT, regardless of stage?
Participants will receive fexinidazole oral treatment for 10 days. Regular blood draws and lumbar punctures will be performed over 12 months to confirm the cure of the disease. Other assessments will include the recording of adverse events, signs and symptoms of the disease, laboratory tests, vital signs, electrocardiograms.
- Being tested
- Fexinidazole
- Keywords
- Trypanosoma Brucei (T. b.) rhodesiense, HAT, Neglected Tropical Disease
- Medical subject headings
- Trypanosomiasis, African, Infections, Neglected Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FexinidazoleDrug
Tablets of 600 mg; Participants with a weight between 20 and 34 kg received 1200 mg (2 tablets) for 4 days, then 600 mg (1 tablet) for 6 days (with food); Participants with a weight of 35 kg and above received 1800 mg (3 tablets) for 4 days, then 1200 mg (2 tablets) for 6 days (with food)
| Study group | Role | What they receive |
|---|---|---|
| Patients with stage 1 r-HAT | Experimental | Patients with stage 1 r-HAT were patients without trypanosomes in the cerebrospinal fluid (CSF) but with trypanosomes in the blood and/or lymph and CSF white blood cells (WBC) ≤5 cells/µL. Patients were to receive fexinidazole orally for 10 days. Receives: Drug: Fexinidazole |
| Patients with stage 2 r-HAT | Experimental | Patients with stage 2 r-HAT were patients with trypanosomes in the CSF (and/or in blood/lymph) and/or CSF WBC >5 cells/µL. Patients were to receive fexinidazole orally for 10 days. Receives: Drug: Fexinidazole |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Evaluable Patients With Stage 2 r-HAT Who Died by the End of Hospitalization, Considering Only Deaths Possibly Related to r-HAT or Fexinidazole
The percentage of patients who died between the first intake of fexinidazole until the End-of-Hospitalization Visit (Day 12-18), considering only deaths possibly related to r-HAT or study treatment as assessed by the Data Safety Monitoring Board (DSMB), was calculated. The World Health Organization(WHO) verbal autopsy questionnaire was used since anatomopathological techniques were not available at the study sites (unless the death occurred at the hospital, in which case the investigator was present). In case of death that was not related to r-HAT nor to the study treatment during the hospitalization, the patient is considered as non-evaluable for efficacy purposes. Any patient who left the hospital without being medically discharged by the site Investigator before the planned End-of-Hospitalization Visit, and for whom no outcome could be retrieved, is also to be considered as non-evaluable.
Measured: 12 to 18 days after start of treatment
Secondary outcomes (10)
Percentage of Evaluable Patients With Stage 2 r-HAT, Whose Treatment Outcome is a Failure at the End of Hospitalization
Treatment outcome at end of hospitalization (Day 12-18) is categorized as success or failure. Failure is defined as any of the following: presence of trypanosomes in any body fluid at end of treatment (Day 11), death related to r-HAT or fexinidazole at end of hospitalization according to the DSMB, or absence of clinical improvement leading to the use of rescue medication. Unrelated deaths are neither success nor failure (the patient is considered non-evaluable for efficacy purposes).
Measured: 12 to 18 days after start of treatment
Percentage of Evaluable Patients With Stage 2 r-HAT, Whose Treatment Outcome is a Failure at 12 Months
Treatment outcome at test of cure (Month 12) is categorized as success or failure. Failure is defined as any of the following: presence of trypanosomes in any body fluid, death related to r-HAT or fexinidazole according to the DSMB, absence of clinical improvement leading to the use of rescue medication, or WBC count in the CSF >20 cells/μL which was unlikely due to causes other than HAT. Unrelated deaths are neither success nor failure (the patient is considered non-evaluable for efficacy purposes).
Measured: 12 months after start of treatment
Percentage of Evaluable Patients With Stage 1 r-HAT, Whose Treatment Outcome is a Failure at the End of Hospitalization
Treatment outcome at end of hospitalization (Day 12-18) is categorized as success or failure. Failure is defined as any of the following: presence of trypanosomes in any body fluid at end of treatment (Day 11), death related to r-HAT or fexinidazole at end of hospitalization according to the DSMB, or absence of clinical improvement leading to the use of rescue medication. Unrelated deaths are neither success nor failure (the patient is considered non-evaluable for efficacy purposes).
Measured: 12 to 18 days after start of treatment
Percentage of Evaluable Patients With Stage 1 r-HAT, Whose Treatment Outcome is a Failure at 12 Months
Treatment outcome at test of cure (Month 12) is categorized as success or failure. Failure is defined as any of the following: presence of trypanosomes in any body fluid, death related to r-HAT or fexinidazole according to the DSMB, absence of clinical improvement leading to the use of rescue medication, or WBC count in the CSF >20 cells/μL which was unlikely due to causes other than HAT. Unrelated deaths are neither success nor failure (the patient is considered non-evaluable for efficacy purposes).
Measured: 12 months after start of treatment
Percentage of Evaluable Patients With Any r-HAT Stage Who Died by the End of Hospitalization, Considering Only Deaths Possibly Related to r-HAT or Fexinidazole
The percentage of patients who died between the first intake of fexinidazole until the End-of-Hospitalization Visit (Day 12-18), considering only deaths possibly related to r-HAT or study treatment as assessed by the DSMB, was calculated. The WHO verbal autopsy questionnaire was used since anatomopathological techniques were not available at the study sites (unless the death occurred at the hospital, in which case the investigator was present). In case of death that was not related to r-HAT nor to the study treatment during the hospitalization, the patient is considered as non-evaluable for efficacy purposes. Any patient who left the hospital without being medically discharged by the site Investigator before the planned End-of-Hospitalization Visit, and for whom no outcome could be retrieved, is also to be considered as non-evaluable.
Measured: 12 to 18 days after start of treatment
Percentage of Evaluable Patients With Any r-HAT Stage, Whose Treatment Outcome is a Failure at the End of Hospitalization
Treatment outcome at end of hospitalization (Day 12-18) is categorized as success or failure. Failure is defined as any of the following: presence of trypanosomes in any body fluid at end of treatment (Day 11), death related to r-HAT or fexinidazole at end of hospitalization according to the DSMB, or absence of clinical improvement leading to the use of rescue medication. Unrelated deaths are neither success nor failure (the patient is considered non-evaluable for efficacy purposes).
Measured: 12 to 18 days after start of treatment
Percentage of Evaluable Patients With Any r-HAT Stage, Whose Treatment Outcome is a Failure at 12 Months
Treatment outcome at test of cure (Month 12) is categorized as success or failure. Failure is defined as any of the following: presence of trypanosomes in any body fluid, death related to r-HAT or fexinidazole according to the DSMB, absence of clinical improvement leading to the use of rescue medication, or WBC count in the CSF >20 cells/μL which was unlikely due to causes other than HAT. Unrelated deaths are neither success nor failure (the patient is considered non-evaluable for efficacy purposes).
Measured: 12 months after start of treatment
Number of Participants With Any AE (Including Abnormal Laboratory or ECG Finding if Considered Clinically Significant) Until the End of Hospitalization
Treatment-emergent AEs during the observation period were recorded from the first intake of fexinidazole (Day 1) until the End-of-Hospitalization Visit (between Day 12 and Day 18).
Measured: 12 to 18 days (between Day 1 and Day 12-18)
Number of Participants With Any AE Considered as Serious Until the End of the Follow-up Period
Treatment-emergent AEs considered as serious were collected from the first intake of fexinidazole (Day 1) until the End-of-Study Visit (Month 12). An AE was considered as serious if resulted in death, was life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability or incapacity, was a congenital anomaly or birth defect, or was an important medical event.
Measured: 12 months (between Day 1 and Month 12)
Number of Participants With Any AE Considered as Possibly Related to Fexinidazole Until the End of the Follow-up Period
Treatment-emergent AEs considered as possibly related to fexinidazole were collected from the first intake of fexinidazole (Day 1) until the End-of-Study Visit (Month 12).
Measured: 12 months (between Day 1 and Month 12)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jun 2019
- Study start29 Sep 2019
- Primary completion30 Nov 2021
- Study completion12 Oct 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Trypanosomiasis, AfricanStudies 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 2/3
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 45 participants (actual)
Sponsor and investigators
- Lead sponsor
- Drugs for Neglected Diseases
- Sponsor type
- University, hospital or other
- Collaborators
- European and Developing Countries Clinical Trials Partnership (EDCTP)
- Responsible party
- Sponsor
- Investigators
- Enock Matovu, Prof, Principal investigator, Makerere University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03974178
- Sponsor's protocol ID
- DNDi-FEX-07-HAT
- Status last verified
- Dec 2024
- First submitted
- 23 May 2019
- Last updated
- 30 Jan 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Matovu E, Nyirenda W, Eriatu A, Alves D, Perdrieu C, Lemerani M, Wamboga C, Lejon V, Seixas J, Signorell A, Reymondier A, Baudin E, Scherrer B, Valverde Mordt O. Fexinidazole as a new oral treatment for human African trypanosomiasis due to Trypanosoma brucei rhodesiense: a prospective, open-label, single-arm, phase 2-3, non-randomised study. Lancet Glob Health. 2025 May;13(5):e910-e919. doi: 10.1016/S2214-109X(25)00016-6.
PubMed 40288400
Study at a glance
From the registry record, last updated by the sponsor on 30 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy and Safety of Fexinidazole in Patients With Human African Trypanosomiasis (HAT) Due to Trypanosoma Brucei Rhodesiense: a Multicentre, Open-label Clinical Trial
- ClinicalTrials.gov ID
- NCT03974178
- Acronym / sponsor ID
- DNDi-FEX-07-HAT
- Keywords
- Trypanosoma Brucei (T. b.) rhodesiense, HAT, Neglected Tropical Disease
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 45 participants (actual)
- Lead sponsor
- Drugs for Neglected DiseasesUniversity, hospital or other
- Collaborators
- European and Developing Countries Clinical Trials Partnership (EDCTP)
- Study start
- 29 Sep 2019 (actual)
- Primary completion
- 30 Nov 2021 (actual)
- Study completion
- 12 Oct 2022 (actual)
- First posted
- 4 Jun 2019 (actual)
- Results
- Posted 30 Jan 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The ultimate goal of this study is to show that fexinidazole offers an alternative over the existing treatments of Human African trypanosomiasis due to Trypanosoma brucei rhodesiense (r-HAT): melarsoprol in patients with stage 2 r-HAT and suramin in patients with stage 1 r-HAT. The main questions it aims to answer are:
- Is the short-term fatality rate and failure rate associated with fexinidazole lower than those of melarsoprol in patients with stage 2 r-HAT?
- Is the long-term failure rate associated with fexinidazole lower than that of melarsoprol in patients with stage 2 r-HAT?
- Can fexinidazole in patients with stage 1 r-HAT replace the treatment with suramin?
- Is fexinidazole treatment safe in patient with r-HAT, regardless of stage?
Participants will receive fexinidazole oral treatment for 10 days. Regular blood draws and lumbar punctures will be performed over 12 months to confirm the cure of the disease. Other assessments will include the recording of adverse events, signs and symptoms of the disease, laboratory tests, vital signs, electrocardiograms.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Patients with stage 1 r-HAT | Experimental | Drug: FexinidazolePatients with stage 1 r-HAT were patients without trypanosomes in the cerebrospinal fluid (CSF) but with trypanosomes in the blood and/or lymph and CSF white blood cells (WBC) ≤5 cells/µL. Patients were to receive fexinidazole orally for 10 days. |
| Patients with stage 2 r-HAT | Experimental | Drug: FexinidazolePatients with stage 2 r-HAT were patients with trypanosomes in the CSF (and/or in blood/lymph) and/or CSF WBC >5 cells/µL. Patients were to receive fexinidazole orally for 10 days. |
Who may qualify
- Ages
- 6 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (8 listed)
- Signed Informed Consent Form (plus assent for children)
- ≥ 6 years old
- ≥ 20 kg body weight
- Ability to ingest at least one complete meal per day (or at least one Plumpy'Nut® sachet)
- Karnofsky index ≥ 40
Key exclusion criteria (5 listed)
- Active clinically relevant medical conditions other than HAT that may jeopardize subject safety or at the investigator discretion may interfere with participation in the study.
- Compromised general health or severely deteriorated general condition, such as severe malnutrition, cardiovascular shock, respiratory distress, or terminal illness
- Patients with severe hepatic impairment (e.g.: clinical signs of cirrhosis or jaundice)
- Known hypersensitivity to fexinidazole, to any nitroimidazole drugs (e.g. metronidazole, tinidazole), or to any of the excipients
- Patients previously enrolled in the study or having already received fexinidazole
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 |
|---|---|---|
| FexinidazoleTablets of 600 mg; Participants with a weight between 20 and 34 kg received 1200 mg (2 tablets) for 4 days, then 600 mg (1 tablet) for 6 days (with food); Participants with a weight of 35 kg and above received 1800 mg (3 tablets) for 4 days, then 1200 mg (2 tablets) for 6 days (with food) | Drug | Patients with stage 1 r-HAT, Patients with stage 2 r-HAT |
Primary outcome
Percentage of Evaluable Patients With Stage 2 r-HAT Who Died by the End of Hospitalization, Considering Only Deaths Possibly Related to r-HAT or Fexinidazole
Time frame: 12 to 18 days after start of treatment
The percentage of patients who died between the first intake of fexinidazole until the End-of-Hospitalization Visit (Day 12-18), considering only deaths possibly related to r-HAT or study treatment as assessed by the Data Safety Monitoring Board (DSMB), was calculated. The World Health Organization(WHO) verbal autopsy questionnaire was used since anatomopathological techniques were not available at the study sites (unless the death occurred at the hospital, in which case the investigator was present). In case of death that was not related to r-HAT nor to the study treatment during the hospitalization, the patient is considered as non-evaluable for efficacy purposes. Any patient who left the hospital without being medically discharged by the site Investigator before the planned End-of-Hospitalization Visit, and for whom no outcome could be retrieved, is also to be considered as non-evaluable.
10 secondary outcomes
Percentage of Evaluable Patients With Stage 2 r-HAT, Whose Treatment Outcome is a Failure at the End of Hospitalization
Time frame: 12 to 18 days after start of treatment
Percentage of Evaluable Patients With Stage 2 r-HAT, Whose Treatment Outcome is a Failure at 12 Months
Time frame: 12 months after start of treatment
Percentage of Evaluable Patients With Stage 1 r-HAT, Whose Treatment Outcome is a Failure at the End of Hospitalization
Time frame: 12 to 18 days after start of treatment
Percentage of Evaluable Patients With Stage 1 r-HAT, Whose Treatment Outcome is a Failure at 12 Months
Time frame: 12 months after start of treatment
Percentage of Evaluable Patients With Any r-HAT Stage Who Died by the End of Hospitalization, Considering Only Deaths Possibly Related to r-HAT or Fexinidazole
Time frame: 12 to 18 days after start of treatment
Percentage of Evaluable Patients With Any r-HAT Stage, Whose Treatment Outcome is a Failure at the End of Hospitalization
Time frame: 12 to 18 days after start of treatment
Percentage of Evaluable Patients With Any r-HAT Stage, Whose Treatment Outcome is a Failure at 12 Months
Time frame: 12 months after start of treatment
Number of Participants With Any AE (Including Abnormal Laboratory or ECG Finding if Considered Clinically Significant) Until the End of Hospitalization
Time frame: 12 to 18 days (between Day 1 and Day 12-18)
Number of Participants With Any AE Considered as Serious Until the End of the Follow-up Period
Time frame: 12 months (between Day 1 and Month 12)
Number of Participants With Any AE Considered as Possibly Related to Fexinidazole Until the End of the Follow-up Period
Time frame: 12 months (between Day 1 and Month 12)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jan 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 40288400Matovu E, Nyirenda W, Eriatu A, Alves D, Perdrieu C, Lemerani M, Wamboga C, Lejon V, Seixas J, Signorell A, Reymondier A, Baudin E, Scherrer B, Valverde Mordt O. Fexinidazole as a new oral treatment for human African trypanosomiasis due to Trypanosoma brucei rhodesiense: a prospective, open-label, single-arm, phase 2-3, non-randomised study. Lancet Glob Health. 2025 May;13(5):e910-e919. doi: 10.1016/S2214-109X(25)00016-6.
- Individual participant dataSharing planned: No
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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.
Enock Matovu, Prof principal investigator
Makerere University
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Fexinidazole in people with Trypanosomiasis, African and Sleeping Sickness, run by Drugs for Neglected Diseases at 2 sites in 2 countries.
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 8 inclusion and 5 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: finished, as of the sponsor's last update on 30 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Malawi, Uganda. 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 combined 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.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 30 Jan 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Percentage of Evaluable Patients With Stage 2 r-HAT Who Died by the End of Hospitalization, Considering Only Deaths Possibly Related to r-HAT or Fexinidazole (time frame: 12 to 18 days after start of treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03974178, which also lists 1 linked publication.
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 Jan 2025.