Phase 2a Trial of Alpibectir Plus Ethionamide for Tuberculosis Meningitis

ConditionTuberculosis Meningitis

Trial statusNot yet recruiting

Trial phasePhase 2

Trial typeInterventional

Biological sexAll

Age15-64

SponsorBioVersys AG

About this trial

AlpE is a novel drug combination under development for the treatment of TB, with several positive attributes for TBM, including rapid bactericidal activity. The current trial aims to assess the plasma and CSF PK, as well as the safety and tolerability of alpibectir and three doses of Eto in patients with newly diagnosed TBM. Additionally, it is attended to investigate the effect of AlpE on the PK and efficacy of DTG during the first month of antiretroviral treatment (ART) for Human Immunodeficiency Virus (HIV)-positive patients.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Age ≥ 15 years and < 65 years

Diagnosis of TBM defined as "definite" or "probable", using criteria proposed by the Tuberculosis Meningitis International Research Consortium.

Definite TBM is defined by at least one of the following criteria: acid-fast bacilli (AFB) seen in CSF microscopy, positive CSF M. tuberculosis culture, or positive CSF M. tuberculosis commercial nucleic acid amplification test in the setting of symptoms suggestive of meningitis.

Probable TBM is defined using a modified Marais score* Probable TBM: total score* ≥ 12 when neuroimaging is available, or ≥ 10 when neuroimaging is not available. At least 2 points should come from CSF or 2 points from cerebral imaging criteria.

Disqualifiers

Having received >14 days of HRZE TB treatment.

In people with HIV infection: use of antiretroviral treatment (ART) other than efavirenz- or dolutegravir-based.

Glasgow Coma Scale < 10.

Body weight measured or estimated: < 40 kg or > 90 kg or BMI > 40 kg/m2.

Trial design

Design model

Parallel

Treatments tested in this trial

HRZE
Drug
Isoniazid (5 mg/kg/day); Rifampicin (10 mg/kg/day); Pyrazinamide (30 mg/kg/day); Ethambutol (20 mg/kg/day).
HRZE plus Alpe375
Drug
isoniazid (5 mg/kg/day); rifampicin (10 mg/kg/day); pyrazinamide (30 mg/kg/day); ethambutol (20 mg/kg/day), Alpe375 (alpibectir (30 mg/day), ethionamide (375 mg/day))
HRZE plus AlpE500
Drug
isoniazid (5 mg/kg/day); rifampicin (10 mg/kg/day); pyrazinamide (30 mg/kg/day); ethambutol (20 mg/kg/day), Alpe375 (alpibectir (30 mg/day), ethionamide (500 mg/day))
HRZE plus AlpE625
Drug
isoniazid (5 mg/kg/day); rifampicin (10 mg/kg/day); pyrazinamide (30 mg/kg/day); ethambutol (20 mg/kg/day), Alpe375 (alpibectir (30 mg/day), ethionamide (625 mg/day))

Treatment groups

64 Participants

are divided into 4 treatment groups

Group A: Group 1: HRZEActive comparator 1 intervention

Group B: Group 2: HRZE plus Alpe375Experimental treatment 1 intervention

Group C: Group 3: HRZE plud AlpE500Experimental treatment 1 intervention

Group D: Group 4: HRZE plus AlpE625Experimental treatment 1 intervention

Trial outcomes

Primary outcomes

To describe the pharmacokinetics (PK) of AlpE in plasma and cerebrospinal fluid (CSF) in patients with newly diagnosed Tuberculosis Meningitis (TBM)

CSF/plasma ratio of alpibectir, ethionamide and the metabolite ethionamide sulfoxide

Time frame

15 days

Secondary outcomes

To assess the safety and tolerability of alpibectir and ethionamide (Eto) in patients with TBM

Incidence of adverse events (AEs), including AEs ≥ grade 3, serious adverse events (SAEs), and AEs leading to AlpE discontinuation between D1 and D56

Time frame

56 days

Other outcomes

To assess the effect of AlpE on the plasma PK of isoniazid (H), rifampicin (R), pyrazinamide (Z), ethambutol (E) (HRZE).

CSF/plasma ratio of HRZE

Time frame

Day 15

To assess the Mycobacterium tuberculosis (Mtb) culture conversion rate

To estimate the Mycobacterium tuberculosis (Mtb) culture conversion rate and time to detection (by MGIT), and cycle threshold (GeneXpert MTB/RIF Ultra) on the CSF and respiratory samples at screening, D3, and D15.

Time frame

15 days

Locations

This trial has no locations.

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

BioVersys AG

Lead sponsor

Source ClinicalTrials.gov

This trial is not recruiting at the moment. You can still explore other options: