NCT05256017: OXA004

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

Completed Phase 2, PHASE3 Results posted Last updated 20 March 2025

What this trial tests

Phase 2, PHASE3 trial testing Acoziborole in Trypanosomiasis, African in 1,208 participants. Completed in 3 August 2023.

Timeline

30 December 2021

Primary endpoint
3 August 2023

3 August 2023

Quick facts

Lead sponsor	Drugs for Neglected Diseases
Phase	Phase 2, PHASE3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	1,208
Start date	30 December 2021
Primary completion	3 August 2023
Estimated completion	3 August 2023
Sites	7 locations across Democratic Republic of the Congo, Guinea

Drugs / interventions tested

• Acoziborole — full drug profile →
• Placebo

Conditions studied

• Trypanosomiasis, African — all drugs for Trypanosomiasis, African →
• Trypanosoma Brucei Gambiense; Infection — all drugs for Trypanosoma Brucei Gambiense; Infection →
• Sleeping Sickness — all drugs for Sleeping Sickness →

Sponsor

Drugs for Neglected Diseases — full company profile →

Who can join

15 and older, any sex, with Trypanosomiasis, African or Trypanosoma Brucei Gambiense; Infection. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Occurrence of Any TEAEs Primary · From the investigational product administration (Day 1) to the Month 4 follow-up visit (End of Study).

Occurrence and excess rate (95% CI) of any TEAEs.

Group	Value	95% CI
Acoziborole	195
Placebo	69

Occurrence of TEAEs - Malaria Primary · From the investigational product administration (Day 1) to the Month 4 follow-up visit (End of Study).

Occurrence and excess rate (95% CI) of common TEAEs (by PT, for PTs reported in ≥1% of participants in either arm).

Group	Value	95% CI
Acoziborole	34
Placebo	14

Occurrence of TEAEs - Acarodermatitis Primary · From the investigational product administration (Day 1) to the Month 4 follow-up visit (End of Study).

Occurrence and excess rate (95% CI) of common TEAEs (by PT, for PTs reported in ≥1% of participants in either arm).

Group	Value	95% CI
Acoziborole	13
Placebo	3

Occurrence of TEAEs - Abdominal Pain Primary · From the investigational product administration (Day 1) to the Month 4 follow-up visit (End of Study).

Occurrence and excess rate (95% CI) of common TEAEs (by PT, for PTs reported in ≥1% of participants in either arm).

Group	Value	95% CI
Acoziborole	23
Placebo	9

Occurrence of TEAEs - Enteritis Primary · From the investigational product administration (Day 1) to the Month 4 follow-up visit (End of Study).

Occurrence and excess rate (95% CI) of common TEAEs (by PT, for PTs reported in ≥1% of participants in either arm).

Group	Value	95% CI
Acoziborole	7
Placebo	4

Occurrence of TEAEs - Nausea Primary · From the investigational product administration (Day 1) to the Month 4 follow-up visit (End of Study).

Occurrence and excess rate (95% CI) of common TEAEs (by PT, for PTs reported in ≥1% of participants in either arm).

Group	Value	95% CI
Acoziborole	7
Placebo	3

Occurrence of TEAEs - Gastritis Primary · From the investigational product administration (Day 1) to the Month 4 follow-up visit (End of Study).

Occurrence and excess rate (95% CI) of common TEAEs (by PT, for PTs reported in ≥1% of participants in either arm).

Group	Value	95% CI
Acoziborole	6
Placebo	3

Occurrence of TEAEs - Headache Primary · From the investigational product administration (Day 1) to the Month 4 follow-up visit (End of Study).

Occurrence and excess rate (95% CI) of common TEAEs (by PT, for PTs reported in ≥1% of participants in either arm).

Group	Value	95% CI
Acoziborole	53
Placebo	8

Occurrence of TEAEs - Fatigue Primary · From the investigational product administration (Day 1) to the Month 4 follow-up visit (End of Study).

Occurrence and excess rate (95% CI) of common TEAEs (by PT, for PTs reported in ≥1% of participants in either arm).

Group	Value	95% CI
Acoziborole	14
Placebo	5

Occurrence of TEAEs - Blood Potassium Increased Primary · From the investigational product administration (Day 1) to the Month 4 follow-up visit (End of Study).

Occurrence and excess rate (95% CI) of common TEAEs (by PT, for PTs reported in ≥1% of participants in either arm).

Group	Value	95% CI
Acoziborole	8
Placebo	6

Occurrence of TEAEs by Period of Occurrence Primary · During hospitalization: from investigational product administration (Day 1) to Day 5 (End of Hospitalization); After hospitalization: from Day 5 (discharge) to the Month 4 follow-up visit (End of Study).

Occurrence and excess rate (95% CI) of any TEAEs, by period of occurrence.

During hospitalization

Group	Value	95% CI
Acoziborole	124
Placebo	38

After hospitalization

Group	Value	95% CI
Acoziborole	106
Placebo	45

Occurrence of Serious TEAEs Primary · From the investigational product administration (Day 1) to the Month 4 follow-up visit (End of Study).

Occurrence and excess rate (95% CI) of any serious TEAEs.

Group	Value	95% CI
Acoziborole	3
Placebo	4

Adverse events — posted to ClinicalTrials.gov

Time frame: From ICF signature (up to 2 days prior treatment) to Month 4 (end of follow-up). Reporting threshold: 1%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Acoziborole

Serious: 3/906 (0%)

Deaths: 0/906

Placebo

Serious: 4/300 (1%)

Deaths: 1/300

Serious adverse events (7 terms)

Reaction	System	Acoziborole	Placebo
Appendicitis	Infections and infestations	—	—
Malaria	Infections and infestations	—	—
Wound infection	Infections and infestations	—	—
Uterine prolapse	Reproductive system and breast disorders	—	—
Vaginal haemorrhage	Reproductive system and breast disorders	—	—
Abortion	Pregnancy, puerperium and perinatal conditions	—	—
Abortion induced	Surgical and medical procedures	—	—

Other adverse events (9 terms — click to expand)

Reaction	System	Acoziborole	Placebo
Headache	Nervous system disorders	—	—
Malaria	Infections and infestations	—	—
Abdominal pain	Gastrointestinal disorders	—	—
Fatigue	General disorders	—	—
Acarodermatitis	Infections and infestations	—	—
Blood potassium increased	Investigations	—	—
Enteritis	Gastrointestinal disorders	—	—
Nausea	Gastrointestinal disorders	—	—
Gastritis	Gastrointestinal disorders	—	—

Most-reported serious reactions: Appendicitis, Malaria, Wound infection, Uterine prolapse, Vaginal haemorrhage, Abortion, Abortion induced.

Data from ClinicalTrials.gov NCT05256017 adverse events section.

Sponsor's own description

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.

Publications & conference data

5 peer-reviewed publications reference this trial (live from Europe PMC):

1. Anti-trypanosomatid drug discovery: progress and challenges.
   De Rycker M, Wyllie S, Horn D, Read KD, et al · · 2023 · cited 112× · PMID 35995950 · DOI 10.1038/s41579-022-00777-y
2. Efficacy and safety of acoziborole in patients with human African trypanosomiasis caused by Trypanosoma brucei gambiense: a multicentre, open-label, single-arm, phase 2/3 trial.
   Betu Kumeso VK, Kalonji WM, Rembry S, Valverde Mordt O, et al · · 2023 · cited 72× · PMID 36460027 · DOI 10.1016/s1473-3099(22)00660-0
3. The pipeline for drugs for control and elimination of neglected tropical diseases: 1. Anti-infective drugs for regulatory registration.
   Pfarr KM, Krome AK, Al-Obaidi I, Batchelor H, et al · · 2023 · cited 20× · PMID 36859332 · DOI 10.1186/s13071-022-05581-4
4. Gambiense human African trypanosomiasis: the bumpy road to elimination.
   Hasker E, Hope A, Bottieau E. · · 2022 · cited 12× · PMID 35942856 · DOI 10.1097/qco.0000000000000860
5. The STROGHAT study protocol: An intervention study to evaluate safety, effectiveness and feasibility of treating gambiense HAT seropositive subjects with acoziborole.
   Nicco E, Lejon V, Mwamba Miaka E, Mumba D, et al · · 2025 · cited 6× · PMID 40191624 · DOI 10.12688/openreseurope.19077.1