Pharmacokinetic, Efficacy, Safety and Tolerability Study of a Single Dose of Acoziborole in g-HAT Paediatric Patients

NCT05433350 | Recruiting Phase 2 DMC

• 2 other identifiers: DNDi-OXA-05-HATACOZI-KIDS
• Study Type: interventional
• Target: 35
• Locations: 2 countries
• Sites: 6

Brief Summary

Acoziborole has been studied in an open-label pivotal Phase II/III trial (DNDi-OXA-02-HAT) in the DRC and Guinea. As the numbers of reported cases diminish, resources for surveillance and specialised screening will also taper. This decrease, coupled with the loss of diagnostic skills and disease management expertise, will lead to a weak and less specialised HAT technical environment. The history of g-HAT has shown that outbreaks or re-emergence of the disease have already happened under different circumstances when surveillance was relaxed or simply because the populations at risk live in areas of political instability, limiting access to specialised care. Even with a steady decrease of reported incidence, no model can currently predict that HAT could not re-emerge. Although g-HAT is predominantly a disease of adults, children are also affected at diverse rates depending on the geographical and behavioural characteristics in the different areas of disease transmission. Hence efforts are needed to develop a paediatric formulation from a new generation of oral HAT treatments.

Conditions

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

Keywords

g-HAT; ACOZI-KIDS

Outcome Measures

Primary Outcomes (8)

• Maximum concentration (Cmax)

  Primary PK parameters in blood

  From time 0 to 96 hours

• Area under the curve (AUC0-96h)

  Primary PK parameters in blood

  From time 0 to 96 hours

• Time to maximum concentration (Tmax)

  Primary PK parameters in blood

  From time 0 to 96 hours

• Area under curve (AUC0-∞)

  Secondary PK parameters in blood

  Day 1 Hour 0, Day 1 Hour 4, Day 1 Hour 9, Day 2 Hour 24, Day 3 Hour 48, Day 4 Hour 72, Day 5 Hour 96, Day 11 Hour 264, month 3 any time

• Clearance

  Secondary PK parameters in blood

  Day 1 Hour 0, Day 1 Hour 4, Day 1 Hour 9, Day 2 Hour 24, Day 3 Hour 48, Day 4 Hour 72, Day 5 Hour 96, Day 11 Hour 264, month 3 any time

• Volume of distribution (Vd)

  Secondary PK parameters in blood

  Day 1 Hour 0, Day 1 Hour 4, Day 1 Hour 9, Day 2 Hour 24, Day 3 Hour 48, Day 4 Hour 72, Day 5 Hour 96, Day 11 Hour 264, month 3 any time

• Half-life (t1/2)

  Secondary PK parameters in blood

  Day 1 Hour 0, Day 1 Hour 4, Day 1 Hour 9, Day 2 Hour 24, Day 3 Hour 48, Day 4 Hour 72, Day 5 Hour 96, Day 11 Hour 264, month 3 any time

• CSF concentration

  Acoziborole concentration in CSF

  Day 11

Secondary Outcomes (8)

• Success or failure

  6 and 12 months post-treatment

• Cumulative risk of proven failure over time (Kaplan-Meyer estimate)

  6 and 12 months post-treatment

• Occurrence of any treatment-emergent adverse events (TEAEs) (any grade) during the observation period

  Day 1 to month 6

• Occurrence of any TEAEs (grade ≥3 or severe) and relatedness to medication during the observation period

  Day 1 to month 6

• Occurrence of any serious adverse events (SAEs) during the study

  Day 1 to month 12

Study Arms (1)

Acoziborole

EXPERIMENTAL

Single dose administration Two different mode of administration will be used depending on the body weight and on the step of the study: * In step 1: 2 tablets of 320 mg (whole) for paediatric patients weighing 30 to 40 kg * In step 2 : whole or crushed tablets (1 or 2 tablets depending on the weight) for paediatric patients weighing 10 to 40 kg. Tablets will be crushed for paediatric patients \< 6 years old and for paediatric patients ≥ 6 years old who are unable to swallow tablets * Initially, recruitment will be limited to paediatric patients weighing 30 to 40 kg who will receive the 2 tablets of 320 mg. * Once the PK data from the first six patients have been analysed and the dosing regimen confirmed or adapted, inclusion will resume and be extended to allow enrolment of paediatric patients weighing \>10 kg.

Drug: Acoziborole

Interventions

Acoziborole DRUG

Two different mode of administration will be used during the study depending on the body weight and on the step of the study: whole tablets of 320 mg dose for paediatric patients weighing 30 to 40 kg in step 1 whole or crushed tablets for paediatric patients weighing 10 to 40 kg in step 2

Acoziborole

Eligibility Criteria

• Age: 1 Year - 14 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Signed informed consent from one parent or from the legal representative
• Assent from the paediatric patient (for paediatric patients \>6 years of age) to participate in the study, collected in the presence of an impartial witness
• Between 1 and 14 years of age and between 10 and ≤40 kg (as per the requirements of step 1 and step 2)
• Male or female
• Evidence of trypanosomes in any body fluid (blood or lymph or CSF)
• Having a permanent address and able to comply with the schedule of follow-up visits
• Agreement to not take part in any other clinical trials during the participation in this study
• For pubescent girls of childbearing potential must agree to have avoid getting pregnant during the screening period and up to 3 months after acoziborole dosing by using an acceptable effective contraception method (sexual abstinence, condom, injectable progestin-only contraceptive)
• Agreement not to continue any treatment (including traditional/herbal medicine) without consulting the investigator
• Agreement not to start a treatment (including traditional/herbal medicine) during 4 months after intake of acoziborole without consulting the Investigator

You may not qualify if:

• Previous treatment for g-HAT
• Refusal to participate in the study, expressed by the paediatric patient and/or parent or legal representative
• Complicated severe acute malnutrition as defined by weight for height (-3 SDs Z score)
• Unable to take medication by the oral route
• Clinically significant medical condition (other than HAT) that could, in the opinion of the Investigator, jeopardise the patient's safety or interfere with participation in the study
• Any condition (excluding HAT-specific symptoms) that affects the patient's and/or parent's ability to communicate with the Investigator as required to complete the study
• Prior enrolment in the study or prior intake of acoziborole
• Foreseeable difficulty complying with follow-up, including family of migrant workers, refugee status, itinerant trader, etc.
• Clinically significant laboratory test abnormality, with:
• Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) more than twice the upper limit of normal (ULN)
• Total bilirubin more than 1.5 x ULN
• Severe leukopenia at \<2000/mm3
• Potassium \<3.5 mmol/L
• Any other clinically significant laboratory test abnormality
• Pregnancy confirmed by a positive urine pregnancy test (during the screening period and/or within 24 hours prior to the start of treatment) for pubescent girls of childbearing potential

Sponsors & Collaborators

• Drugs for Neglected Diseases: lead

Study Sites (6)

General Hospital of Bandundu

Bandundu Province, Bandundu, Democratic Republic of the Congo

RECRUITING

CDTC Katanda

Katanda, East Kasai, Democratic Republic of the Congo

RECRUITING

Hôpital Général de Dipumba

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

RECRUITING

HGR Bagata

Bagata, Kwilu, Democratic Republic of the Congo

RECRUITING

Hospital of Masi-Manimba

Masi-Manimba, Kwilu, Democratic Republic of the Congo

RECRUITING

General Referral Hospital of Dubreka

Dubréka, Guinea

RECRUITING

Related Links

• ACOZI-KIDS project on DNDi website

MeSH Terms

Conditions

Trypanosomiasis, African; Infections

Condition Hierarchy (Ancestors)

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

Study Officials

• Victor Kande Betu Ku Mesu, Dr

  Ministry of Public Health, Hygiene and Prevention, Kinshasa

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Junior Matangila, Dr

CONTACT

+243 97 075 68 90; jmatangila@dndi.org

Adeline Prêtre

CONTACT

+41 22 907 77 22; apretre@dndi.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 15, 2022
• First Posted: June 27, 2022
• Study Start: July 9, 2022
• Primary Completion: March 31, 2026
• Study Completion: March 31, 2026
• Last Updated: March 23, 2026

Record last verified: 2026-03

Locations

GU (1); DE (5)