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

NCT05256017 | Completed Phase 2 Results DMC

• 1 other identifier: DNDi-OXA-04-HAT
• Study Type: interventional
• Target: 1,208
• Locations: 2 countries
• Sites: 7

Brief 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.

Conditions

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

Keywords

Human African Trypanosomiasis; Trypanosoma Brucei Gambiense; Sleeping sickness; g-HAT; g-HAT seropositive individuals

Outcome Measures

Primary Outcomes (15)

• Occurrence of Any TEAEs

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

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

• Occurrence of TEAEs - Malaria

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

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

• Occurrence of TEAEs - Acarodermatitis

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

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

• Occurrence of TEAEs - Abdominal Pain

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

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

• Occurrence of TEAEs - Enteritis

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

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

• Occurrence of TEAEs - Nausea

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

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

• Occurrence of TEAEs - Gastritis

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

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

• Occurrence of TEAEs - Headache

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

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

• Occurrence of TEAEs - Fatigue

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

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

• Occurrence of TEAEs - Blood Potassium Increased

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

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

• Occurrence of TEAEs by Period of Occurrence

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

  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 of Serious TEAEs

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

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

• Occurrence of Severe Treatment-related TEAEs

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

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

• Occurrence of Any Treatment-related TEAEs

  Occurrence of any treatment-related TEAEs by arm

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

• Occurrence of Treatment-related TEAEs by PT

  Occurrence of any treatment-related TEAEs by PT and by arm

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

Secondary Outcomes (27)

• Occurrence of Adverse Events (AEs)

  From Inform Consent signature (up to 2 days before treatment) to the Month 4 follow up visit (End of Study)

• Change From Baseline in Biochemistry Parameter: Alanine Aminotransferase

  From baseline to the Month 4 follow-up visit (End of Study).

• Change From Baseline in Biochemistry Parameter: Albumin

  From baseline to the Month 4 follow-up visit (End of Study).

• Change From Baseline in Biochemistry Parameter: Alkaline Phosphatase

  From baseline to the Month 4 follow-up visit (End of Study).

• Change From Baseline in Biochemistry Parameter: Aspartate Aminotransferase

  From baseline to the Month 4 follow-up visit (End of Study).

Study Arms (2)

Acoziborole

EXPERIMENTAL

Single dose administration of acoziborole, 3 tablets of 320 mg

Drug: Acoziborole

Placebo

PLACEBO COMPARATOR

Single dose administration of acoziborole matching placebo, 3 tablets of 320 mg

Drug: Placebo

Interventions

Acoziborole DRUG

Single dose administration of acoziborole (3 tablets of 320 mg) on Day 1

Acoziborole

Placebo DRUG

Single dose administration of placebo (3 tablets of 320 mg) on Day 1

Placebo

Eligibility Criteria

• Age: 15 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed the informed consent form (ICF)
• Male or female
• 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)

You may not qualify if:

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

Sponsors & Collaborators

• Drugs for Neglected Diseases: lead

Study Sites (7)

General Referral Hospital of Bagata

Bagata, Bandundu, Democratic Republic of the Congo

Location

Hospital of Dipumba

Mbuji-Mayi, East Kasai, Democratic Republic of the Congo

Location

General Referral Hospital of Idiofa

Idiofa, Kwilu, Democratic Republic of the Congo

Location

General Referral Hospital of Masi-Manimba

Masi-Manimba, Kwilu, Democratic Republic of the Congo

Location

General Referral Hospital of Kwamouth

Kwamouth, Mai Ndombe, Democratic Republic of the Congo

Location

General Referral Hospital of Bandundu

Bandundu Province, Democratic Republic of the Congo

Location

General Referral Hospital of Dubreka

Dubréka, Guinea

Location

MeSH Terms

Conditions

Trypanosomiasis, African; Infections

Condition Hierarchy (Ancestors)

Trypanosomiasis; Euglenozoa Infections; Protozoan Infections; Parasitic Diseases; Vector Borne Diseases

Limitations and Caveats

No limitations or caveats were identified.

Results Point of Contact

• Title: Dr Junior Matanglia
• Organization: Drugs for Neglected Disease initiative (DNDi)

jmatangila@dndi.org

+243 970 756 890

Study Officials

• Victor Kande Betu Kumeso, Dr.

  Ministry of Public Health, Hygiene and Prevention, Kinshasa

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-blind, placebo controlled study
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Unbalanced, randomized (ratio of 3:1 \[acoziborole:placebo\]) parallel-arm study. Study treatment (acoziborole or placebo) administered on Day 1. Post-treatment hospitalization of 5 days (up to Day 5). Follow-up visits scheduled at Month 1 and Month 4 (End of Study visit).

Study Record Dates

• First Submitted: January 17, 2022
• First Posted: February 25, 2022
• Study Start: December 30, 2021
• Primary Completion: August 3, 2023
• Study Completion: August 3, 2023
• Last Updated: March 20, 2025
• Results First Posted: March 20, 2025

Record last verified: 2025-02

Locations

GU (1); DE (6)