Human African Trypanosomiasis (HAT)Phase 2/3NCT01685827
Pivotal Study of Fexinidazole for Human African Trypanosomiasis in Stage 2
A Phase 2/3 study testing Fexinidazole, Nifurtimox and Eflornithine in people with Human African Trypanosomiasis (HAT) and Sleeping Sickness, run by Drugs for Neglected Diseases at 10 sites in 3 countries.
Trial summary
This clinical trial is designed to prove the efficacy and safety of Fexinidazole as an oral treatment for human african trypanosomiasis in advanced stage. The Fexinidazole is compared to reference treatment NECT. The trial will try to demonstrate that Fexinidazole is not inferior to NECT treatment. Read more about this study
- Who is it for?
- Ages 15 years and older
- Conditions the study is for
- Human African Trypanosomiasis (HAT), Sleeping Sickness
- What is being tested?
- Fexinidazole, Nifurtimox and Eflornithine
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 394 participants
- Where
- 10 sitesin 3 countries
- Study dates
- Oct 2012to 26 Apr 2017
- Phase
- Phase 2/3
- 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 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 15 years old or more
- Male or female
- Able to ingest at least one complete meal per day (or at least one Plumpy'Nut® sachet)
- Karnofsky index>50 (see Appendix 2 - Karnofsky Scale; p81)
- Parasitologically confirmed late-stage African trypanosomiasis infection with T. b. gambiense in the blood and/or lymph and/or CSF, attested by mobile team report (with detail of exams performed and values of WBC measured in CSF) or done at the study centre. If parasitologically negative in CSF, WBC >20/µl detected in the CSF to document stage 2 infection.
- Having a permanent address and able to comply with follow-up visit schedule
- Signed Informed Consent Form
Who cannot join
- Severely malnourished patients, defined as having a BMI < 16.
- Patients unable to take oral medication.*
- Pregnancy or lactation
- Active clinically relevant medical conditions that, in the Investigator's opinion, may jeopardize subject safety or interfere with participation in the study, including but not limited to significant liver or cardiovascular disease, active documented or suspected infection, CNS trauma or seizure disorders, coma or altered consciousness.
- Severely deteriorated general condition, such as cardiovascular shock, respiratory distress, or terminal illness.
- Any condition which compromises ability to communicate with the Investigator as required for the completion of this study.
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- Any contraindication to imidazole products (known hypersensitivity to imidazoles) and NECT (known hypersensitivity to eflornithine).
- Patients previously treated for HAT.
- Patients previously enrolled in the study.
- Follow-up expectable difficulties (migrants, refugees, traders, etc.).
- History of alcohol abuse or any drug addiction.
- Clinically significant abnormal laboratory value
- Pregnancy
- Unstable ECG abnormalities
- QTcF≥ 450 msec in resting position (confirmed by 2 measurement).
- Patients not tested for malaria and/or treated adequately for this infection
- Patients not treated adequately for soil transmitted helminthic diseases
Trial locations and contacts
10 sites in 3 countries.
10 sites in 3 countries
Republic of the Congo8 sites
HGR (General Reference Hospital) Bandundu
Bandundu, Bandundu
Dingila
Dingila
HGR ISANGI hospital
Isangi, Province Orientale
HS Katanda hospital
Katanda, Kasaï Oriental
Masi Manimba Hospital
Masi Manimba, Bandundu - DRC
CRT (Centre de Réference et de Traitement) Dipumba, Dipumba general hospital
Mbuji Mayi, East Kasai
HGR Mushie hospital
Mushie, Bandundu
Vanga Hospital
Vanga, Bandundu - DRC
Central African Republic1 site
Batangafo
Batangafo
Democratic Republic of the Congo1 site
Bagata Hospital
Bagata, Bandundu
About this study
Official title: Efficacy and Safety of Fexinidazole Compared to Nifurtimox-Eflornithine Combination Therapy (NECT) in Patients With Late-stage Human African Trypanosomiasis (HAT) Due to T.b. Gambiense: Pivotal, Non-inferiority, Multicentre, Randomised, Open-label Study
This clinical trial is designed to prove the efficacy and safety of Fexinidazole as an oral treatment for human african trypanosomiasis in advanced stage. The Fexinidazole is compared to reference treatment NECT. The trial will try to demonstrate that Fexinidazole is not inferior to NECT treatment.
Read the detailed description
Human African Trypanosomiasis (HAT) is a life-threatening and neglected disease.
Few treatment options are currently available for stage 2 (meningo-encephalitic stage) HAT, with NECT being the most commonly used one since 2010. Though NECT represents a significant improvement over current therapies, it is still far from ideal given the environment in which HAT patients live (remote, poor areas with little health infrastructure, if any, and difficult logistics). There is an urgent need for less toxic and more easily manageable compounds to treat this fatal disease.
Fexinidazole is a 2-5-nitroimidazole, formulated for oral administration, which has been shown to possess in vitro and in vivo activity against both T. b. rhodesiense and T. b. gambiense parasites.
Predicted CSF concentrations reached target levels after repeated dosing. Its efficacy and safety must now be tested in patients with stage 2 HAT.
- Being tested
- Fexinidazole, Nifurtimox, Eflornithine
- Medical subject headings
- Trypanosomiasis, African
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FexinidazoleDrug
NifurtimoxDrug
Also called Lampit
EflornithineDrug
Also called Ornidyl
| Study group | Role | What they receive |
|---|---|---|
| NECT (Nifurtimox Eflornithine Combination Therapy) | Active comparator | * Nifurtimox tablets will be given orally three times a day, at the daily dose of 15 mg/kg/day, for 10 days.
* Eflornithine (400 mg/kg/day) will be given twice daily for 7 days, as a 2-hour IV infusion. Receives: Drug: Nifurtimox; Drug: Eflornithine |
| Fexinidazole | Experimental | Fexinidazole, 600 mg tablets given by oral route, after the main daily meal (within 30 minutes from the start of the meal), at the daily dose of:
* 1 800 mg (3 tablets) once a day for 4 days,
* Followed by 1 200 mg (2 tablets) once a day for 6 days. Total duration of treatment will be 10 days. Receives: Drug: Fexinidazole |
What is being measured
The primary outcome is the main question the study is designed to answer.
success or failure at 18 months FU visit
The primary endpoint is the outcome (success or failure) at the test of cure (ToC) visit 18 months after the end of treatment (EOT) adapted from WHO criteria.
Success at 18 months is:
- Either cure:
- patient alive,
- AND with no evidence of trypanosomes in any body fluid,
- AND 20 or less WBC/µl CSF
- Or Probable cure:
- Patient with no parasitological evidence of relapse in blood and lymph
- AND who refuses lumbar puncture OR whose CSF sample is haemorrhagic without trypanosomes
- AND whose clinical condition is satisfactory (without clinical symptom or signs) OR whose clinical status is unlikely to be due to HAT
Measured: 18 months after treatment
Secondary outcomes (4)
Safety endpoint
Occurrence of any grade (all grades combined) adverse events during the observation period (D1-18) including:
- any worsening of clinical symptoms listed in the inclusion checklist of symptoms and signs,
- laboratory abnormalities of grade ≥ 2
- Occurrence of grade ≥ 3 adverse events during the observation period
- Occurrence of drug-related adverse events (grade ≥ 3 and any grade) during the observation period
Measured: 18 days - observation period
Safety endpoint
Occurrence of any serious adverse events from first drug intake to the end of follow-up period (18 months), and from M18 to M24.
Measured: 24 months
Pharmacokinetics endpoint
Whole blood and CSF concentrations of fexinidazole, M1, M2 and PK parameters derived from a model of population PK data.
Measured: from D8 to D12 after first dosing
QT evaluation
recording of triplicates ECG
Measured: D0 - D4 - D10
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Sep 2012 (estimated)
- Study startOct 2012
- Primary completion11 Nov 2016
- Study completion26 Apr 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Human African Trypanosomiasis (HAT)Studies 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 394 participants (actual)
Sponsor and investigators
- Lead sponsor
- Drugs for Neglected Diseases
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Victor KANDE, MD, Principal investigator, HAT National Control Program in DRC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01685827
- Sponsor's protocol ID
- DNDiFEX004
- Status last verified
- Feb 2018
- First submitted
- 12 Sep 2012
- Last updated
- 20 Feb 2018
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Mesu VKBK, Kalonji WM, Bardonneau C, Mordt OV, Blesson S, Simon F, Delhomme S, Bernhard S, Kuziena W, Lubaki JF, Vuvu SL, Ngima PN, Mbembo HM, Ilunga M, Bonama AK, Heradi JA, Solomo JLL, Mandula G, Badibabi LK, Dama FR, Lukula PK, Tete DN, Lumbala C, Scherrer B, Strub-Wourgaft N, Tarral A. Oral fexinidazole for late-stage African Trypanosoma brucei gambiense trypanosomiasis: a pivotal multicentre, randomised, non-inferiority trial. Lancet. 2018 Jan 13;391(10116):144-154. doi: 10.1016/S0140-6736(17)32758-7. Epub 2017 Nov 4.
PubMed 29113731
Study at a glance
From the registry record, last updated by the sponsor on 20 Feb 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy and Safety of Fexinidazole Compared to Nifurtimox-Eflornithine Combination Therapy (NECT) in Patients With Late-stage Human African Trypanosomiasis (HAT) Due to T.b. Gambiense: Pivotal, Non-inferiority, Multicentre, Randomised, Open-label Study
- ClinicalTrials.gov ID
- NCT01685827
- Acronym / sponsor ID
- DNDiFEX004
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 394 participants (actual)
- Lead sponsor
- Drugs for Neglected DiseasesUniversity, hospital or other
- Study start
- Oct 2012
- Primary completion
- 11 Nov 2016 (actual)
- Study completion
- 26 Apr 2017 (actual)
- First posted
- 14 Sep 2012 (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 clinical trial is designed to prove the efficacy and safety of Fexinidazole as an oral treatment for human african trypanosomiasis in advanced stage. The Fexinidazole is compared to reference treatment NECT. The trial will try to demonstrate that Fexinidazole is not inferior to NECT treatment.
Detailed description
Human African Trypanosomiasis (HAT) is a life-threatening and neglected disease.
Few treatment options are currently available for stage 2 (meningo-encephalitic stage) HAT, with NECT being the most commonly used one since 2010. Though NECT represents a significant improvement over current therapies, it is still far from ideal given the environment in which HAT patients live (remote, poor areas with little health infrastructure, if any, and difficult logistics). There is an urgent need for less toxic and more easily manageable compounds to treat this fatal disease.
Fexinidazole is a 2-5-nitroimidazole, formulated for oral administration, which has been shown to possess in vitro and in vivo activity against both T. b. rhodesiense and T. b. gambiense parasites.
Predicted CSF concentrations reached target levels after repeated dosing. Its efficacy and safety must now be tested in patients with stage 2 HAT.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| NECT (Nifurtimox Eflornithine Combination Therapy) | Active comparator | Drug: Nifurtimox, Drug: Eflornithine* Nifurtimox tablets will be given orally three times a day, at the daily dose of 15 mg/kg/day, for 10 days. * Eflornithine (400 mg/kg/day) will be given twice daily for 7 days, as a 2-hour IV infusion. |
| Fexinidazole | Experimental | Drug: FexinidazoleFexinidazole, 600 mg tablets given by oral route, after the main daily meal (within 30 minutes from the start of the meal), at the daily dose of: * 1 800 mg (3 tablets) once a day for 4 days, * Followed by 1 200 mg (2 tablets) once a day for 6 days. Total duration of treatment will be 10 days. |
Who may qualify
- Ages
- 15 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (7 listed)
- 15 years old or more
- Male or female
- Able to ingest at least one complete meal per day (or at least one Plumpy'Nut® sachet)
- Karnofsky index>50 (see Appendix 2 - Karnofsky Scale; p81)
- Parasitologically confirmed late-stage African trypanosomiasis infection with T. b. gambiense in the blood and/or lymph and/or CSF, attested by mobile team report (with detail of exams performed and values of WBC measured in CSF) or done at the study centre. If parasitologically negative in CSF, WBC >20/µl detected in the CSF to document stage 2 infection.
Key exclusion criteria (17 listed)
- Severely malnourished patients, defined as having a BMI < 16.
- Patients unable to take oral medication.*
- Pregnancy or lactation
- Active clinically relevant medical conditions that, in the Investigator's opinion, may jeopardize subject safety or interfere with participation in the study, including but not limited to significant liver or cardiovascular disease, active documented or suspected infection, CNS trauma or seizure disorders, coma or altered consciousness.
- Severely deteriorated general condition, such as cardiovascular shock, respiratory distress, or terminal illness.
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 |
|---|---|---|
| Fexinidazole | Drug | Fexinidazole |
| NifurtimoxAlso: Lampit | Drug | NECT (Nifurtimox Eflornithine Combination Therapy) |
| EflornithineAlso: Ornidyl | Drug | NECT (Nifurtimox Eflornithine Combination Therapy) |
Primary outcome
success or failure at 18 months FU visit
Time frame: 18 months after treatment
The primary endpoint is the outcome (success or failure) at the test of cure (ToC) visit 18 months after the end of treatment (EOT) adapted from WHO criteria. Success at 18 months is: * Either cure: * patient alive, * AND with no evidence of trypanosomes in any body fluid, * AND 20 or less WBC/µl CSF * Or Probable cure: * Patient with no parasitological evidence of relapse in blood and lymph * AND who refuses lumbar puncture OR whose CSF sample is haemorrhagic without trypanosomes * AND whose clinical condition is satisfactory (without clinical symptom or signs) OR whose clinical status is unlikely to be due to HAT
4 secondary outcomes
Safety endpoint
Time frame: 18 days - observation period
Safety endpoint
Time frame: 24 months
Pharmacokinetics endpoint
Time frame: from D8 to D12 after first dosing
QT evaluation
Time frame: D0 - D4 - D10
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Feb 2018.
- Derived from this study: PubMed 29113731Mesu VKBK, Kalonji WM, Bardonneau C, Mordt OV, Blesson S, Simon F, Delhomme S, Bernhard S, Kuziena W, Lubaki JF, Vuvu SL, Ngima PN, Mbembo HM, Ilunga M, Bonama AK, Heradi JA, Solomo JLL, Mandula G, Badibabi LK, Dama FR, Lukula PK, Tete DN, Lumbala C, Scherrer B, Strub-Wourgaft N, Tarral A. Oral fexinidazole for late-stage African Trypanosoma brucei gambiense trypanosomiasis: a pivotal multicentre, randomised, non-inferiority trial. Lancet. 2018 Jan 13;391(10116):144-154. doi: 10.1016/S0140-6736(17)32758-7. Epub 2017 Nov 4.
- Sponsor WebsiteLink provided by the sponsor.
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.
Victor KANDE, MD principal investigator
HAT National Control Program in DRC
10 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Fexinidazole, Nifurtimox and Eflornithine in people with Human African Trypanosomiasis (HAT) and Sleeping Sickness, run by Drugs for Neglected Diseases at 10 sites in 3 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 7 inclusion and 17 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 20 Feb 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in Republic of the Congo, Central African Republic, Democratic Republic of the Congo. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
success or failure at 18 months FU visit (time frame: 18 months after 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 NCT01685827, 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 20 Feb 2018.