Phase 3 N=1,208 Randomized Quadruple-blind Treatment

Safety and Tolerability Study of Acoziborole in g-HAT Seropositive Subjects

Trypanosomiasis, African · Trypanosoma Brucei Gambiense; Infection · Sleeping Sickness

Bottom Line

View on ClinicalTrials.gov: NCT05256017 ↗

Enrolled (actual)

1,208

Serious AEs

0.6%

Results posted

Mar 2025

Primary outcome: Primary: Occurrence of Any TEAEs — 195; 69 Participants

Study Design & Population

Study type: Interventional
Phase: Phase 3
Interventions: Acoziborole (Drug); Placebo (Drug)
Age: Pediatric, Adult, Older Adult · 15+ yrs
Sex: All
Sponsor: Drugs for Neglected Diseases
Primary completion: Aug 2023

Outcome Measures

Outcome	Result	p-value
PRIMARY Occurrence of Any TEAEs	195; 69	—
PRIMARY Occurrence of TEAEs - Malaria	34; 14	—
PRIMARY Occurrence of TEAEs - Acarodermatitis	13; 3	—
PRIMARY Occurrence of TEAEs - Abdominal Pain	23; 9	—
PRIMARY Occurrence of TEAEs - Enteritis	7; 4	—
PRIMARY Occurrence of TEAEs - Nausea	7; 3	—
PRIMARY Occurrence of TEAEs - Gastritis	6; 3	—
PRIMARY Occurrence of TEAEs - Headache	53; 8	—
PRIMARY Occurrence of TEAEs - Fatigue	14; 5	—
PRIMARY Occurrence of TEAEs - Blood Potassium Increased	8; 6	—
PRIMARY Occurrence of TEAEs by Period of Occurrence	124; 38; 106; 45	—
PRIMARY Occurrence of Serious TEAEs	3; 4	—
PRIMARY Occurrence of Severe Treatment-related TEAEs	0; 0	—
PRIMARY Occurrence of Any Treatment-related TEAEs	59; 17	—
PRIMARY Occurrence of Treatment-related TEAEs by PT	28; 5; 14; 6; 8; 5	—
SECONDARY Occurrence of Adverse Events (AEs)	195; 69	—
SECONDARY Change From Baseline in Biochemistry Parameter: Alanine Aminotransferase	20.6; 20.6; 21.9; 24.9; 19.2; 19.5	—
SECONDARY Change From Baseline in Biochemistry Parameter: Albumin	3.22; 3.23; 3.12; 3.13; 3.27; 3.24	—
SECONDARY Change From Baseline in Biochemistry Parameter: Alkaline Phosphatase	99.8; 101.8; 91.9; 95.7; 96.6; 98.3	—
SECONDARY Change From Baseline in Biochemistry Parameter: Aspartate Aminotransferase	32.8; 32.7; 33.8; 37.2; 31.0; 32.6	—
SECONDARY Change From Baseline in Biochemistry Parameter: Calcium	2.314; 2.322; 2.279; 2.328; 2.305; 2.298	—
SECONDARY Change From Baseline in Biochemistry Parameter: Chloride	105.3; 105.3; 105.2; 105.2; 105.1; 105.0	—
SECONDARY Change From Baseline in Biochemistry Parameter: Creatinine	0.84; 0.84; 0.83; 0.81; 0.82; 0.81	—
SECONDARY Change From Baseline in Biochemistry Parameter: Glucose	88.581; 87.087; 89.801; 89.410; 91.715; 90.207	—
SECONDARY Change From Baseline in Biochemistry Parameter: Potassium	4.58; 4.60; 4.67; 4.59; 4.61; 4.60	—
SECONDARY Change From Baseline in Biochemistry Parameter: Sodium	136.7; 136.7; 137.2; 137.1; 137.2; 137.1	—
SECONDARY Change From Baseline in Biochemistry Parameter: Total Bilirubin	0.879; 0.869; 0.739; 0.809; 0.818; 0.884	—
SECONDARY Change From Baseline in Biochemistry Parameter: Bicarbonate	27.5; 27.5; 28.5; 28.2; 28.0; 27.7	—
SECONDARY Change From Baseline in Biochemistry Parameter: Total Protein	7.63; 7.65; 7.46; 7.61; 7.55; 7.59	—
SECONDARY Change From Baseline in Biochemistry Parameter: Blood Urea Nitrogen	7.434; 7.415; 8.402; 8.358; 6.951; 6.820	—
SECONDARY Change From Baseline in Hematology Parameter: Hemoglobin	13.09; 13.10; 12.57; 12.95; 12.78; 13.00	—
SECONDARY Change From Baseline in Hematology Parameter: Platelet Count	229.1; 229.0; 230.5; 226.5; 227.7; 227.6	—
SECONDARY Change From Baseline in Hematology Parameter: Leukocytes	5.53; 5.46; 5.64; 5.60; 5.51; 5.50	—
SECONDARY Change From Baseline in ECG (Electrocardiogram) Parameter: Heart Rate (HR)	66.8; 70.0; 66.4; 69.1; -0.4; -0.9	—
SECONDARY Change From Baseline in ECG Parameter: RR Interval	921.6; 882.2; 923.5; 893.7; 1.9; 11.5	—
SECONDARY Change From Baseline in ECG Parameter: PR Interval	162.4; 162.2; 161.4; 161.9; -1.0; -0.3	—
SECONDARY Change From Baseline in ECG Parameter: QRS Interval	82.2; 82.3; 81.8; 82.5; -0.5; 0.3	—
SECONDARY Change From Baseline in ECG Parameter: QT Interval	389.5; 383.0; 377.3; 383.1; -12.1; 0.1	—
SECONDARY Change From Baseline in ECG Parameter: QTcF	401.3; 400.5; 388.5; 399.0; -12.8; -1.5	—
SECONDARY Change From Baseline in ECG Parameter: QTcB	407.9; 410.1; 394.6; 407.8; -13.3; -2.3	—
SECONDARY Placebo-corrected Baseline-adjusted QTcF (ΔΔQTcF), Computed From a Concentration-response (C-R) Model Between Dry Blood Spot Concentration and Changes From Baseline in QTcF Parameter	-12.9	—
SECONDARY Incidence of Abnormal Values for PR, QRS, QTcB and QTcF According to Pre-defined Thresholds	0; 0; 0; 0; 6; 2	—

Summary

Human African trypanosomiasis (HAT) or sleeping sickness is a tropical disease which is endemic in sub-Saharan Africa. Most cases of HAT are due to the parasite Trypanosoma brucei gambiense (T.b. gambiense), which is transmitted by the bite of the tsetse fly. HAT can be fatal without diagnosis and treatment. Several treatment options are currently available to treat HAT caused by the T.b. gambiense parasite (g-HAT), but these treatments can be administered only after demonstrating via microscopy the presence of the parasite in a body fluid. However, there are factors such as low parasitaemia and the complexity and low sensitivity of parasitological methods that make such demonstration difficult. It has been demonstrated that a variable proportion (mainly depending on the prevalence) of such g-HAT "sero-suspects" are confirmed cases and, therefore, remain potential reservoirs of the parasite and a source of new infections hindering the efforts to eliminate the disease. The drug acoziborole was evaluated in a study called "DNDi-OXA-02-HAT". During this study, patients with g-HAT from the DRC and Guinea took a single dose of acoziborole. This study showed that acoziborole has a high efficacy and is safe for treating patients with confirmed g-HAT . The present study is called "DNDi-OXA-04-HAT". It included seropositive participants from the DRC and Guinea who did not have parasites detected via microscopy in a body fluid. Its objective was to collect data on the safety and tolerability of a single dose of acoziborole compared to a placebo (i.e. a dummy treatment). The results of this study would help decide if acoziborole can be used in the population of g-HAT seropositive individuals and help eliminate the HAT disease.

Eligibility Criteria

Inclusion Criteria

Signed the informed consent form (ICF)
Male or female
15 years of age or older
Card agglutination test for trypanosomiasis (CATT) test or HAT sero-K-set rapid diagnostic test (RDT) positive
Parasitology negative (in blood and/or lymph node aspirate [if lymphadenopathy is present])
Karnofsky performance status above 70
Able to ingest oral tablets
Known address and/or contact details provided
Able to comply with the schedule of follow-up visits and other requirements of the study
Agreement to be hospitalized upon enrolment for at least 5 days (in order to receive in-ward post-treatment observational follow-up through the first 5 days after treatment)
Agreement to not take part in any other clinical trials during the participation in this study
For women of childbearing potential:
Agreed to have protected sexual relations to avoid becoming pregnant from enrolment up to 3 months after dosing (contraceptive protection was advised and offered at no cost)
Negative urine pregnancy tests (before dosing at site level)

Exclusion Criteria

Individuals parasitologically confirmed in blood and/or lymph
Previously treated for g-HAT
Severe malnutrition, defined as body mass index (BMI) <16 kg/m^2
Pregnant or breast-feeding women
For women of childbearing potential:
Urine pregnancy test positive
Did not accept contraceptive protection (i.e. condom or sexual abstinence) from enrolment up to 3 months after dosing
Clinically significant medical condition and/or abnormal laboratory results that could, in the opinion of the Investigator, jeopardize the participant's safety or participation in the study

Additional exclusion criteria for the TrypSkin exploratory sub-study:

Rejection to participate in the exploratory sub-study in the signed ICF
Known diabetes mellitus
Known hemophilia

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT05256017). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.