Prospective Study on Efficacy and Safety of Acoziborole (SCYX-7158) in Patients Infected by Human African Trypanosomiasis Due to T.b. Gambiense (OXA002)

Efficacy and Safety Study of Acoziborole (SCYX-7158) in Patients With Human African Trypanosomiasis (HAT) Due to Trypanosoma Brucei Gambiense: a Multicentre, Open-label, Prospective Study

The goal of this study is to assess efficacy and safety of Acoziborole (SCYX-7158) given as a single dose oral treatment for adult patients (above or equal 15) in the fasting state with T.b. Gambiense HAT

Study Overview

• Status: Completed
• Conditions: Trypanosomiasis, African; Gambiense Trypanosomiasis; Sleeping Sickness
• Intervention / Treatment: Drug: Acoziborole (SCYX-7158)

• Study Type: Interventional
• Enrollment (Actual): 260
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Congo, The Democratic Republic of the
  • Bandundu, Congo, The Democratic Republic of the
    • Hopital Général de réference de Bandundu
  • Isangi, Congo, The Democratic Republic of the
    • Hôpital de référence d'Isangi
  • Kinshasa, Congo, The Democratic Republic of the
    • Hôpital Général de Référence Roi Baudouin
  • Bandundu
    • Nkara, Bandundu, Congo, The Democratic Republic of the
      • Centre de Traitement de NKara
  • Bas Congo
    • Kimpese, Bas Congo, Congo, The Democratic Republic of the
      • Centre de Traitement de Kimpese
  • Kasai Oriental
    • Gandajika, Kasai Oriental, Congo, The Democratic Republic of the
      • Hôpital Général de Référence de NGandajika
  • Kasai-Oriental
    • Mbuji-Mayi, Kasai-Oriental, Congo, The Democratic Republic of the
      • Hôpital de Dipumba
  • Kasaï-Oriental
    • Katanda, Kasaï-Oriental, Congo, The Democratic Republic of the
      • Hôpital secondaire de Katanda
  • Kwilu
    • Bagata, Kwilu, Congo, The Democratic Republic of the
      • Hopital General de réference de Bagata
    • Masi-Manimba, Kwilu, Congo, The Democratic Republic of the
      • Hôpital Général de Référence de Masi-Manimba
  • Mai-Ndombe
    • Kwamouth, Mai-Ndombe, Congo, The Democratic Republic of the
      • Hôpital Généal de référence de Kwamouth
• Guinea
  • Dubreka
    • Dubréka, Dubreka, Guinea
      • Centre de Traitement de la THA de Dubreka

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female patient
• 15 years of age or older
• Signed informed consent form (as well as assent from illiterate and under-age patients, and those unable to give consent)
• Karnofsky Performance Status above 50
• Able to ingest oral tablets
• Having a permanent address or being traceable by other persons
• Able to comply with the schedule of follow-up visits and requirements of the study
• Agreement to be hospitalised in order to receive treatment

• For patients with late-stage HAT:

  • Confirmation of g-HAT by detection of the parasite in the blood and/or the lymph and/or the CSF, at the investigational centre
  • If trypanosomes are found in the blood or lymph, but not in the CSF, the CSF WBC, measured at the investigational centre, must be above 20/μL for the patient to be included in the cohort of patients with late-stage HAT

• For patients with early- or intermediate-stage HAT:

  • Confirmation of g-HAT by detection of the parasite in the blood and/or the lymph, at the investigational centre
  • Absence of parasites in the CSF
  • The CSF WBC, measured at the investigational centre, must be between 6 and 20/μL for the patient to be included in the cohort of patients with intermediate-stage HAT and equal to or below 5/μL for the patient to be included in the cohort of patients with early-stage HAT.

Exclusion Criteria:

• Severe malnourishment, defined as body-mass index (BMI) below 16
• Pregnancy or breastfeeding (for women of child-bearing potential, confirmed pregnancy on a urine pregnancy test performed within 24 hours prior to administration of SCYX-7158)
• Clinically significant medical condition that could, in the opinion of the Investigator, jeopardise the patient's safety or interfere with participation in the study, including, but not limited to significant liver or cardiovascular disease, suspected or proven active infection, central nervous system trauma or seizure disorder, coma or consciousness disturbances
• Severely deteriorated health status, e.g. due to cardiovascular shock, respiratory distress syndrome or end-stage disease
• Previously treated for HAT (except prior treatment with pentamidine)
• Prior enrolment in the study
• Foreseeable difficulty complying with follow-up, including migrant worker, refugee status, itinerant trader etc.
• Current alcohol abuse or drug addiction
• Not tested for malaria and/or not having received appropriate treatment for malaria
• Not having received appropriate treatment for soil-transmitted helminthiasis
• Clinically significant abnormal laboratory values including Aspartate AminoTransferase(AST) and/or AlanineAminoTransferase (ALT) more than 2 times the upper limit of normal (ULN), total bilirubin more than 1.5 ULN, severe leukopenia at less than 2000/mm3, Potassium below 3.5 mmol/L, any other clinically significant abnormal laboratory value

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Acoziborole (SCYX-7158); Acoziborole (SCYX-7158), in 320-mg tablets, administered by the oral route to patients in the fasting state according to the following dosing regimen: 960 mg (3 tablets) in a single intake on Day 1.	Drug: Acoziborole (SCYX-7158)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Success or failure for patients in late stage HAT	Success is defined as a cure, according to the criteria adapted from the World Health Organization(WHO)	18 months follow up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Success or failure for all stage HAT patients	Success is defined as a cure, according to the criteria adapted from the WHO	6, 12 and 18 months follow up
Time to Failure in Patients with Late-stage HAT	Time of the first objective evidence of failure.	18 months follow up
Occurence of adverse events	Occurrence of any Adverse Event, including an abnormal laboratory test result, during the observation period and until 6 month follow-up.	From day 1 until 6 months follow-up
Occurence of serious advers events	Occurrence of any serious adverse events during the observation period and until 18 month follow-up	Between the day 1 and the end of the follow-up period (18 month)
Pharmacokinetics measure	SCYX-7158 Area Under Curve in whole blood and in the Cerebrospinal fluid (CSF);	Days 1, 2, 3, 4, 5, 11, Month 3 and Month 6 follow up visits
Pharmacokinetics measure	SCYX-7158 concentration in whole blood and in the Cerebrospinal fluid;	Days 1, 2, 3, 4, 5, 11, Month 3 and Month 6 follow up visits
Electrocardiogram measure	PR interval	Days 1, 2, 3, 4, 5 and 11
Electrocardiogram measure	quantitative description of PR interval	Days 1, 2, 3, 4, 5 and 11
Electrocardiogram measure	quantitative description of RR interval	Days 1, 2, 3, 4, 5 and 11
Electrocardiogram measure	quantitative description of QRs interval	Days 1, 2, 3, 4, 5 and 11
Electrocardiogram measure	quantitative description of QTcF interval	Days 1, 2, 3, 4, 5 and 11

Collaborators and Investigators

• Sponsor: Drugs for Neglected Diseases
• Investigators: Principal Investigator: Victor Kande Betu Kumeso, Dr, Ministère de la Santé

Study record dates

Study Major Dates

• Study Start (Actual): October 11, 2016
• Primary Completion (Actual): August 28, 2020
• Study Completion (Actual): August 28, 2020

Study Registration Dates

• First Submitted: March 7, 2017
• First Submitted That Met QC Criteria: March 16, 2017
• First Posted (Actual): March 23, 2017

Study Record Updates

• Last Update Posted (Actual): January 19, 2022
• Last Update Submitted That Met QC Criteria: January 17, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Vector Borne Diseases; Parasitic Diseases; Protozoan Infections; Euglenozoa Infections; Trypanosomiasis; Trypanosomiasis, African
• Other Study ID Numbers: DNDi-OXA-02-HAT

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Only for patients from OXA002 participating also in the DiTECT-HAT-WP4, some data (all anonymised) will be shared with L'Institut de Recherche pour le Dévelopment, sponsor of the DiTECT-HAT-WP4 study.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No