Tuberculous MeningitisPhase 2BPaLMZNCT07227779
BPaLMZ for TB Meningitis
A Phase 2 study testing BPaLMZ Regimen in people with Tuberculous Meningitis and HIV, run by David Boulware at 2 sites in Uganda.
Trial summary
This two-stage study will compare consented research participants with tuberculous meningitis receiving experimental Bedaquiline (B), Pretomanid (Pa), Linezolid (L); Moxifloxacin (M), Pyrazinamide (Z) known as (BPaLMZ) to controls receiving SOC of rifampicin (R), isoniazid (H), pyrazinamide (Z), and ethambutol (E)… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Tuberculous Meningitis, HIV, Meningitis
- What is being tested?
- BPaLMZ Regimen
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 312 participants
- Where
- 2 sitesUganda
- Study dates
- 28 Jul 2026to 30 Sep 2030
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- First Episode definite or probable TBM with physician intent to treat
- Age ≥18 years
- Provision of Informed Consent by participant or surrogate
- Living with HIV
- Weight > 35kg, estimate or measured
Who cannot join
- Additional active and confirmed CNS infection
- Known rifampicin-resistant TB
- Allergy or contraindication to a study medicine
- More than 5 doses of any TB therapy received within the previous 14 days
- Presence of jaundice, known liver cirrhosis, elevated ALT or AST >3x ULN, or total bilirubin >2x ULN
- Estimated Glomerular Filtration Rate <30 ml/min/1.73m2
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- Significant cardiac comorbidity, heart failure, arrhythmia, or QTc >450 ms
- Pregnancy or Breastfeeding
- Cryptococcal antigen positivity in blood
- Condition which makes participation not in the participant's best interest
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Uganda2 sites, 2 recruiting
- Recruiting
Infectious Diseases Institute
Kampala
Suzan Namombwe, MBChB, snamombwe@idi.co.ug
David B Meya, MBChB, MMed, PhD
- Recruiting
Mbarara University of Science and Technology
Mbarara
Conrad Muzoora, MBChB MMed, 256772547175, conradmuzoora@gmail.com
About this study
Official title: A PHASE 2 NOVEL ANTIMICROBIAL COMBINATION THERAPY TO TREAT TUBERCULOUS MENINGITIS
This two-stage study will compare consented research participants with tuberculous meningitis receiving experimental Bedaquiline (B), Pretomanid (Pa), Linezolid (L); Moxifloxacin (M), Pyrazinamide (Z) known as (BPaLMZ) to controls receiving SOC of rifampicin (R), isoniazid (H), pyrazinamide (Z), and ethambutol (E), known as RHZE. The experimental regimen is known as 1BPaLMZ/5PaM.
Read the detailed description
1BPaLMZ/5PaM regimen for TB meningitis
- Conditions
- Tuberculous Meningitis, HIV, Meningitis, TB - Tuberculosis
- Being tested
- BPaLMZ Regimen
- Keywords
- TB meningitis
- Medical subject headings
- Tuberculosis, Meningeal, Meningitis, Latent Tuberculosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BPaLMZ RegimenDrug
bedaquiline, pretomanid, linezolid, moxifloxacin, and pyrazinamide
| Study group | Role | What they receive |
|---|---|---|
| BPaLMZ Regimen | Experimental | bedaquiline, pretomanid, linezolid, moxifloxacin, and pyrazinamide (BPaLMZ) Receives: Drug: BPaLMZ Regimen |
| Standard of Care Regimen | No intervention | rifampicin, isoniazid, pyrazinamide, ethambutol (RHZE) therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
24-week Survival
Survival Time
Measured: 24 Weeks
Hierarchical composite endpoint (survival time + functional status)
Hierarchical composite endpoint of survival time and Rankin score (0-5 scale) assessed by Win Ratio
Measured: 24 Weeks
Secondary outcomes (14)
Serious adverse events (SAE)
Incidience of Serious adverse events
Measured: 28 weeks
Clinical Adverse Events
Clinical Adverse Events, by grade (1-5) associated with TB drug discontinuation, dose reduction, or interruption >=3 days
Measured: 28 weeks
Laboratory abnormalities
Number of participants with grade 3 or 4 abnormal laboratory values, by the Division of AIDS toxicity grading scale
Measured: 28 weeks
Neuropathy
Incidence of Neuropathy
Measured: 28 weeks
Drug induced liver injury
Drug induced liver injury with Grade >=3 with serum alanine aminotransferase (ALT) >5x upper limit or normal or total bilirubin >2.5x upper limit of normal)
Measured: 28 weeks
Change in CSF inflammatory markers
Change in CSF leukocytes from baseline to day 7 and 14 visits.
Measured: 14 days
Modified Rankin Scale
Modified Rankin Score as an ordinal score (0-6 scale) of:
0 Alive: no residual symptoms or disability.
- No significant disability: symptoms are present but do not prevent carrying out all usual duties and activities; able to carry out all pre-TBM activities.
- Slight disability: unable to carry out all pre-TBM activities but able to look after self without daily help.
- Moderate disability: requires some assistance with tasks but able to walk without assistance.
- Moderately severe disability: unable attend to bodily functions or walk without assistance.
- Severe disabilities: bedridden, incontinent, requires continuous care and attention.
- Dead
Measured: 24 weeks
Change in blood inflammatory markers
Change in white blood cell count from baseline to day 7 visit
Measured: 7 days
Quantitative neurocognitive performance Z-score
Quantitative neurocognitive performance Z-score scaled to Ugandan population adult norms where population average = 0. Performance is Z-scored such that performance that is one standard deviation better than average is +1 and one standard deviation worse is -1.
Measured: 24 weeks
Change in PCR cycle threshold (Ct) value in CSF
Change in PCR cycle threshold (Ct) value in CSF from baseline to Day 7 and 14 visits.
Measured: 14 days
Altered Mental Status over time
Number of days with Glasgow Coma Scale score = 15 within the first 10 days
Measured: 10 days
Additional corticosteroids use
Additional corticosteroids use in TBM survivors (beyond initial use)
Measured: 24 weeks
Change in CSF glcuose
Change in CSF glucose from baseline to day 7 to day 14
Measured: 14 days
Change in serum C-reactive protein
Change in serum C-reactive protein (CRP) from baseline to day 7
Measured: 7 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Nov 2025
- Study start28 Jul 2026
- Primary completion31 Mar 2028 (estimated)
- Study completion30 Sep 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Tuberculous 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
- Model description
- Phase 2a consists of n = 40 single arm BPaLMZ participants. Phase 2b consists of n = 272 randomized participants.
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 312 participants (estimated)
Sponsor and investigators
- Lead sponsor
- David Boulware
- Sponsor type
- University, hospital or other
- Collaborators
- Infectious Diseases Institute, Uganda, University of Minnesota, Brighton & Sussex Medical School, Mbarara University of Science and Technology, Radboud University Medical Center, Meningitis Foundation
- Responsible party
- Sponsor-investigator, David Boulware, University of Minnesota
- Investigators
- David Boulware, MD, Principal investigator, University of Minnesota
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07227779
- Sponsor's protocol ID
- STUDY00024610
- Acronym
- BPaLMZ
- Status last verified
- Oct 2026
- First submitted
- 11 Nov 2025
- Last updated
- 16 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: deidentified dataset
Study at a glance
From the registry record, last updated by the sponsor on 16 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A PHASE 2 NOVEL ANTIMICROBIAL COMBINATION THERAPY TO TREAT TUBERCULOUS MENINGITIS
- ClinicalTrials.gov ID
- NCT07227779
- Acronym / sponsor ID
- BPaLMZ / STUDY00024610
- Conditions
- Tuberculous Meningitis, HIV, Meningitis, TB - Tuberculosis
- Keywords
- TB meningitis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 312 participants (estimated)
- Lead sponsor
- David BoulwareUniversity, hospital or other
- Collaborators
- Infectious Diseases Institute, Uganda, University of Minnesota, Brighton & Sussex Medical School, Mbarara University of Science and Technology, Radboud University Medical Center, Meningitis Foundation
- Study start
- 28 Jul 2026 (actual)
- Primary completion
- 31 Mar 2028 (estimated)
- Study completion
- 30 Sep 2030 (estimated)
- First posted
- 13 Nov 2025 (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.
This two-stage study will compare consented research participants with tuberculous meningitis receiving experimental Bedaquiline (B), Pretomanid (Pa), Linezolid (L); Moxifloxacin (M), Pyrazinamide (Z) known as (BPaLMZ) to controls receiving SOC of rifampicin (R), isoniazid (H), pyrazinamide (Z), and ethambutol (E), known as RHZE. The experimental regimen is known as 1BPaLMZ/5PaM.
Detailed description
1BPaLMZ/5PaM regimen for TB meningitis
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
- Model description
- Phase 2a consists of n = 40 single arm BPaLMZ participants. Phase 2b consists of n = 272 randomized participants.
| Arm | Type | Receives |
|---|---|---|
| BPaLMZ Regimen | Experimental | Drug: BPaLMZ Regimenbedaquiline, pretomanid, linezolid, moxifloxacin, and pyrazinamide (BPaLMZ) |
| Standard of Care Regimen | No intervention | –rifampicin, isoniazid, pyrazinamide, ethambutol (RHZE) therapy |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- First Episode definite or probable TBM with physician intent to treat
- Age ≥18 years
- Provision of Informed Consent by participant or surrogate
- Living with HIV
- Weight > 35kg, estimate or measured
Key exclusion criteria (10 listed)
- Additional active and confirmed CNS infection
- Known rifampicin-resistant TB
- Allergy or contraindication to a study medicine
- More than 5 doses of any TB therapy received within the previous 14 days
- Presence of jaundice, known liver cirrhosis, elevated ALT or AST >3x ULN, or total bilirubin >2x ULN
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 |
|---|---|---|
| BPaLMZ Regimenbedaquiline, pretomanid, linezolid, moxifloxacin, and pyrazinamide | Drug | BPaLMZ Regimen |
Primary outcome
24-week Survival
Time frame: 24 Weeks
Survival Time
Hierarchical composite endpoint (survival time + functional status)
Time frame: 24 Weeks
Hierarchical composite endpoint of survival time and Rankin score (0-5 scale) assessed by Win Ratio
14 secondary outcomes
Serious adverse events (SAE)
Time frame: 28 weeks
Clinical Adverse Events
Time frame: 28 weeks
Laboratory abnormalities
Time frame: 28 weeks
Neuropathy
Time frame: 28 weeks
Drug induced liver injury
Time frame: 28 weeks
Change in CSF inflammatory markers
Time frame: 14 days
Modified Rankin Scale
Time frame: 24 weeks
Change in blood inflammatory markers
Time frame: 7 days
Quantitative neurocognitive performance Z-score
Time frame: 24 weeks
Change in PCR cycle threshold (Ct) value in CSF
Time frame: 14 days
Altered Mental Status over time
Time frame: 10 days
Additional corticosteroids use
Time frame: 24 weeks
Change in CSF glcuose
Time frame: 14 days
Change in serum C-reactive protein
Time frame: 7 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 16 Oct 2026.
- Individual participant dataSharing planned: Yes. deidentified dataset
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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.
David Boulware, MD principal investigator
University of Minnesota
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing BPaLMZ Regimen in people with Tuberculous Meningitis and HIV, run by David Boulware at 2 sites in Uganda.
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 5 inclusion and 10 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: looking for participants now, as of the sponsor's last update on 16 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Uganda. Whether a site is taking part right now should be confirmed with that site. See every site.
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?
Contact David Boulware, MD (612-624-9996, coat.trial@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
24-week Survival (time frame: 24 Weeks). The study lists 2 primary outcomes in all. 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 16 Oct 2026.