Pan African Clinical Trials Registry
South African Medical Research Council, South African Cochrane Centre
PO Box 19070, Tygerberg, 7505, South Africa
Telephone: +27 21 938 0506 / +27 21 938 0834 Fax: +27 21 938 0836
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR202011638938739 Date of Approval: 25/11/2020
Trial Status: Retrospective registration - This trial was registered after enrolment of the first participant
TRIAL DESCRIPTION
Public title Efficacy and safety of fexinidazole in patients with Human African Trypanosomiasis (HAT) due to Trypanosoma brucei rhodesiense: a multicentre, open-label clinical trial
Official scientific title Efficacy and safety of fexinidazole in patients with Human African Trypanosomiasis (HAT) due to Trypanosoma brucei rhodesiense: a multicentre, open-label clinical trial
Brief summary describing the background and objectives of the trial No similar project has been done before. To date, only one drug, melarsoprol, is available for late-stage (meningoencephalitic stage) r-HAT. The use of this arsenic-based drug is associated with severe adverse drug reactions, the most important being an encephalopathic syndrome, which occurs in an average 8.0% of T.b. rhodesiense patients, with a case fatality rate of 57%. Patients treated with melarsoprol need to be hospitalized. Furthermore, melarsoprol-monotherapy could be prone to the development of parasite resistance to the drug in the long term, as already observed in the T. b. gambiense endemic region of northwestern Uganda. In a declaration for the elimination of HAT due to T.b. rhodesiense, WHO stakeholders urged for a safe, effective and preferably oral treatment [2]. Fexinidazole was identified by DNDi out of hundreds of nitroimidazole compounds as a promising anti-protozoal drug candidate for the treatment of sleeping sickness. The ultimate goal of this study is to provide evidence for the safety and efficacy of fexinidazole for Tb rhodesiense HAT.
Type of trial CCT
Acronym (If the trial has an acronym then please provide) FEX007
Disease(s) or condition(s) being studied Infections and Infestations
Sub-Disease(s) or condition(s) being studied Human African trypanosomiasis
Purpose of the trial Treatment: Drugs
Anticipated trial start date 01/09/2019
Actual trial start date 29/09/2019
Anticipated date of last follow up 03/10/2022
Actual Last follow-up date 12/10/2022
Anticipated target sample size (number of participants) 50
Actual target sample size (number of participants) 45
Recruitment status Completed
Publication URL
Secondary Ids Issuing authority/Trial register
NCT03974178 clinicaltrial.gov
STUDY DESIGN
Intervention assignment Allocation to intervention If randomised, describe how the allocation sequence was generated Describe how the allocation sequence/code was concealed from the person allocating the participants to the intervention arms Masking If masking / blinding was used
Crossover: all participants receive all interventions in different sequence during study Non-randomised Numbered containers Open-label(Masking Not Used)
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group Fexinidazole • Patients with a body weight ≥ 35 kg:  1800 mg (3 tablets) from day 1 to 4  1200 mg (2 tablets) from day 5 to 10 • Patients with a body weight ≥ 20 and < 35 kg:  1200 mg (2 tablets) from day 1 to 4  600 mg (1 tablet) from day 5 to 10 10 days Fexinidazole, 600 mg tablets, given orally, once daily for 10 days, right after the main meal and preferably at the same time every day and only during hospitalisation. 50
Control Group Fexinidazole 10 days Only one intervention arm 50 Active-Treatment of Control Group
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
• 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 confirmed 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 • 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 (e.g. Patients at risk of QT interval prolongations, cf. details listed in IB section Possible Risk), • Compromised general health or severely deteriorated general condition, such as severe malnutrition, cardiovascular shock, respiratory distress, or terminal illness • 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 • Patients with severe hepatic impairment (ex: clinical signs of cirrhosis or jaundice) 80 and over: 80+ Year,Adolescent: 13 Year-18 Year,Adult: 19 Year-44 Year,Aged: 65+ Year(s),Child: 6 Year-12 Year,Middle Aged: 45 Year(s)-64 Year(s) 6 Year(s) 100 Year(s) Both
ETHICS APPROVAL
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 07/01/2019 National Health Science Research Ethics Committee
Ethics Committee Address
Street address City Postal code Country
MINISTRY OF HEALTH P.O. BOX 30377 Lilongwe 30377 Malawi
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 17/04/2019 Vector control division research ethics committee
Ethics Committee Address
Street address City Postal code Country
15 bombo road. PO box 1661 Kampala 1661 Uganda
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Possibly Related fatality rate at the end of hospitalisation in stage 2 r-HAT patients treated with fexinidazole (death possibly related to r-HAT or treatment according to DSMB; since at the study sites anatomopathological techniques are not available, the completion of the WHO verbal autopsy questionnaire will be requested in case of death) End of Hospitalization
Secondary Outcome 1. Success rate at the end of treatment in stage 1 and stage 2 r-HAT patients, where success is defined as: no trypanosomes at EoT and patient alive at EoH. Failure is defined as presence of trypanosomes in any body fluid at EoT or death at EoH. Deaths to be considered are defined as possibly related to r-HAT or treatment according to DSMB. Unrelated deaths are neither success nor failure. End of Hospitalization
Secondary Outcome 2. Success and failure outcomes at the test-of-cure (ToC) visit 12 months after the end of treatment (EOT). A modification of the WHO recommendations is used to determine success and failure for stage-1 and stage-2 r-HAT patients (Appendix 2 - Evaluation criteria of efficacy endpoints) End of Treatment
Secondary Outcome 3. Occurrence of adverse events, including abnormal laboratory or ECG findings, during the observation period (until the end of hospitalisation scheduled up to 7 days after EOT) and those considered as possibly related to r-HAT or treatment, among those detected until the end of the follow-up period (12-month visit). All serious adverse events (SAE) whether they are considered as possibly related to r-HAT treatment or not. End of study
Secondary Outcome 4. Unsatisfactory clinical and parasitological response, defined as the compound analysis of the evolution of signs and symptoms as well as laboratory tests during the observation period and at the end of treatment visit. End of Treatment
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Rumphi Post Office Box 225 Rumphi Malawi
Lwala Soroti Catholic Diocese, Kaberamaido District, P.O Box 650 Lwala Uganda
FUNDING SOURCES
Name of source Street address City Postal code Country
EDCTP PO Box 93015 The Hague 2509 Netherlands
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Drugs for Neglected Diseases initiative chemin Louis Dunant 15 Geneva 1202 Switzerland Charities/Societies/Foundation
COLLABORATORS
Name Street address City Postal code Country
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Enock Matovu matovue04@yahoo.com 0025677550226 Makerere University, P.O. Box 7072 Wandegeya
City Postal code Country Position/Affiliation
Kampala 22418 Uganda Associate Professor
Role Name Email Phone Street address
Scientific Enquiries Olaf Valverde ovalverde@dndi.org 0041229069239 15 Chemin Louis-Dunant
City Postal code Country Position/Affiliation
Geneva 1202 Switzerland Medical Manager
Role Name Email Phone Street address
Public Enquiries Olaf Valverde ovalverde@dndi.org 0041229069239 15 Chemin Louis-Dunant
City Postal code Country Position/Affiliation
Geneva 1202 Switzerland Medical Manager
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes Summary results will be available on clinicaltrials.gov Clinical Study Report document will be available in Q3 2023, after study completion Access will be controlled and request assessed by DNDi Medical responsible person
URL Results Available Results Summary Result Posting Date First Journal Publication Date
No
Result Upload 1: Result Upload 2: Result Upload 3: Result Upload 4: Result Upload 5:
Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information