Phase 2a Trial of Alpibectir Plus Ethionamide for Tuberculosis Meningitis
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: HRZE, HRZE plus Alpe375, HRZE plus AlpE500, HRZE plus AlpE625.
- Who it may be relevant to
- Registry conditions: Tuberculosis Meningitis. Basic parameters: 15 years — 64 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- Center list to be confirmed — check the primary protocol.
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
Unsure about the terms? Read our patient guide →
Official title
A Multicenter, Open-label, Randomized, Active-controlled, Phase 2a Study to Evaluate the Pharmacokinetics and Safety of Alpibectir/Ethionamide in Combination With the Standard Regimen in Patients With Tuberculosis Meningitis.
Overview
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.
Interventions
- Drug HRZE
Isoniazid (5 mg/kg/day); Rifampicin (10 mg/kg/day); Pyrazinamide (30 mg/kg/day); Ethambutol (20 mg/kg/day). - Drug HRZE plus Alpe375
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)) - Drug HRZE plus AlpE500
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)) - Drug HRZE plus AlpE625
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))
Primary outcome measures
- To describe the pharmacokinetics (PK) of AlpE in plasma and cerebrospinal fluid (CSF) in patients with newly diagnosed Tuberculosis Meningitis (TBM) [Time frame: 15 days]
Secondary outcome measures (1)
- To assess the safety and tolerability of alpibectir and ethionamide (Eto) in patients with TBM [Time frame: 56 days]
Eligibility criteria
Inclusion criteria
- 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.
(\*see Appendix 2: Modified Marais Score)
- Informed consent signed by the patient. For patients with Glasgow Coma Scale (GCS) < 15, the consent of a next of kin/relative will be required, in accordance with applicable local laws and regulations. Deferred consent will be obtained from the participant when their level of consciousness improves, and they have capacity to provide consent. For adolescents below the age of civil majority (as defined in each country), the consent of at least one parent or legal guardian and the assent of the adolescent will be required.
Exclusion criteria
- 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.
- Renal failure (eGFR < 30 mL/min, calculated by CKD-EPI formula).
- Alanine aminotransferase (ALT) > 5 times the Upper Limit of Normal.
- Clinical evidence of liver failure or decompensated cirrhosis.
- For women of childbearing potential, one or more of the following:
- Being pregnant, breast-feeding, or intending to breast-feed or conceive a child during the study or within 30 days after the end of treatment visit (D56), OR;
- Not willing or able to use highly effective contraceptive methods (as defined per Appendix 7) starting at screening and continuing until 30 days after the end of treatment visit (D56).
- For male participants: intending to conceive a child or not willing or able to consistently use a barrier method e.g. condoms during all sexual activity from inclusion until 90 days after the end of treatment visit (D56).
Note: Male participants should be advised of the benefit for a female partner to use a highly effective method of contraception as a condom may break or leak when having sexual intercourse.
- Documented Mtb resistance to rifampicin.
- Positive Gram-stain, bacterial culture other than Mtb or cryptococcal antigen in the CSF.
- For HIV positive patients: Presence of cryptococcal antigen in the blood.
- Inability to collect CSF or contraindication to lumbar puncture (LP).
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- Randomized
- Model
- Parallel assignment
- Masking
- Open label
- Primary purpose
- Treatment
Study locations
Center list to be confirmed — check the primary protocol.
Identifiers
NCT: NCT07350174 · AlpE-TBM