Tuberculosis MeningitisPhase 2NCT07350174
Phase 2a Trial of Alpibectir Plus Ethionamide for Tuberculosis Meningitis
A Phase 2 study testing HRZE, HRZE plus Alpe375 and HRZE plus AlpE500 in people with Tuberculosis Meningitis, run by BioVersys AG.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 15 to 64 years
- Conditions the study is for
- Tuberculosis Meningitis
- What is being tested?
- HRZE, HRZE plus Alpe375 and HRZE plus AlpE500
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 64 participants
- Where
- No sites listed yet
- Study dates
- 30 Mar 2026to 30 Oct 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 15 to 64 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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).
About this study
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.
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.
- Conditions
- Tuberculosis Meningitis
- Being tested
- HRZE, HRZE plus Alpe375, HRZE plus AlpE500, HRZE plus AlpE625
- Keywords
- Tuberculosis, AlpE, Ethionamide, CSF, pharmacokinetics
- Medical subject headings
- Tuberculosis, Meningeal, Tuberculosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HRZEDrug
Isoniazid (5 mg/kg/day); Rifampicin (10 mg/kg/day); Pyrazinamide (30 mg/kg/day); Ethambutol (20 mg/kg/day).
HRZE plus Alpe375Drug
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 AlpE500Drug
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 AlpE625Drug
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))
| Study group | Role | What they receive |
|---|---|---|
| Group 1: HRZE | Active comparator | Not described Receives: Drug: HRZE |
| Group 2: HRZE plus Alpe375 | Experimental | Not described Receives: Drug: HRZE plus Alpe375 |
| Group 3: HRZE plud AlpE500 | Experimental | Not described Receives: Drug: HRZE plus AlpE500 |
| Group 4: HRZE plus AlpE625 | Experimental | Not described Receives: Drug: HRZE plus AlpE625 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 15 days
Secondary outcomes (1)
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
Measured: 56 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jan 2026
- Study start30 Mar 2026 (estimated)
- Primary completion30 Mar 2028 (estimated)
- Study completion30 Oct 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Tuberculosis MeningitisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 64 participants (estimated)
Sponsor and investigators
- Lead sponsor
- BioVersys AG
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07350174
- Sponsor's protocol ID
- AlpE-TBM
- Status last verified
- Jan 2026
- First submitted
- 16 Jan 2026
- Last updated
- 3 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT07350174
- Acronym / sponsor ID
- AlpE-TBM
- Conditions
- Tuberculosis Meningitis
- Keywords
- Tuberculosis, AlpE, Ethionamide, CSF, pharmacokinetics
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 64 participants (estimated)
- Lead sponsor
- BioVersys AGIndustry (pharma, biotech, devices)
- Study start
- 30 Mar 2026 (estimated)
- Primary completion
- 30 Mar 2028 (estimated)
- Study completion
- 30 Oct 2028 (estimated)
- First posted
- 20 Jan 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Group 1: HRZE | Active comparator | Drug: HRZE |
| Group 2: HRZE plus Alpe375 | Experimental | Drug: HRZE plus Alpe375 |
| Group 3: HRZE plud AlpE500 | Experimental | Drug: HRZE plus AlpE500 |
| Group 4: HRZE plus AlpE625 | Experimental | Drug: HRZE plus AlpE625 |
Who may qualify
- Ages
- 15 to 64 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (6 listed)
- Age ≥ 15 years and < 65 years
- Diagnosis of TBM defined as "definite" or "probable", using criteria proposed by the Tuberculosis Meningitis International Research Consortium.
- (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.
Key exclusion criteria (16 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| HRZEIsoniazid (5 mg/kg/day); Rifampicin (10 mg/kg/day); Pyrazinamide (30 mg/kg/day); Ethambutol (20 mg/kg/day). | Drug | Group 1: HRZE |
| HRZE plus Alpe375isoniazid (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 | Group 2: HRZE plus Alpe375 |
| HRZE plus AlpE500isoniazid (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 | Group 3: HRZE plud AlpE500 |
| HRZE plus AlpE625isoniazid (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)) | Drug | Group 4: HRZE plus AlpE625 |
Primary outcome
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
CSF/plasma ratio of alpibectir, ethionamide and the metabolite ethionamide sulfoxide
1 secondary outcome
To assess the safety and tolerability of alpibectir and ethionamide (Eto) in patients with TBM
Time frame: 56 days
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Mar 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing HRZE, HRZE plus Alpe375 and HRZE plus AlpE500 in people with Tuberculosis Meningitis, run by BioVersys AG.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 3 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Mar 2026.