BPaLMZ for TB Meningitis

Not yet recruiting at 1 trial location

Overseen By Darlisha Williams, MPH

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Minnesota

Disqualifiers: CNS infection, Rifampicin-resistant TB, Liver cirrhosis, Cardiac comorbidity, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment plan called BPaLMZ, a combination drug regimen, for individuals with tuberculous meningitis—a serious brain infection caused by tuberculosis—who also have HIV. The study compares the effectiveness of BPaLMZ against the usual treatment, RHZE. Individuals diagnosed with their first episode of tuberculous meningitis and living with HIV might be suitable candidates for this trial. Participants should not have other brain infections or allergies to the study medicines. As a Phase 2 trial, this research focuses on evaluating the treatment's effectiveness in an initial, smaller group of people.

Do I need to stop my current medications to join the trial?

The trial information does not specify if you need to stop your current medications. However, if you have taken more than 5 doses of any TB therapy in the last 14 days, you may not be eligible to participate.

Is there any evidence suggesting that the BPaLMZ regimen is likely to be safe for humans?

A previous study demonstrated promising safety results for the BPaLMZ treatment. Only 11% of participants in the treatment group experienced problems, compared to 48% in the group receiving standard treatment. Additionally, those taking BPaLMZ reported fewer side effects, suggesting that most patients can tolerate it well. The combination of drugs in BPaLMZ—bedaquiline, pretomanid, linezolid, moxifloxacin, and pyrazinamide—has been used in other studies to treat drug-resistant tuberculosis, providing some confidence in its safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about the BPaLMZ regimen for TB meningitis because it combines several powerful drugs: bedaquiline, pretomanid, linezolid, moxifloxacin, and pyrazinamide. Unlike the standard treatment, which typically includes rifampicin, isoniazid, pyrazinamide, and ethambutol, BPaLMZ includes newer drugs like bedaquiline and pretomanid that have shown promise in tackling resistant strains of tuberculosis. This innovative combination aims to enhance efficacy and potentially shorten treatment duration, offering hope for better outcomes in a challenging condition.

What evidence suggests that the BPaLMZ regimen might be an effective treatment for TB meningitis?

This trial will compare the BPaLMZ treatment regimen with the standard of care regimen for TB meningitis. Research has shown that the BPaLMZ treatment, which includes bedaquiline, pretomanid, linezolid, moxifloxacin, and pyrazinamide, holds promise for treating tuberculosis (TB) meningitis. In earlier studies, only 11% of patients experienced poor outcomes with this treatment, compared to 48% with the usual care, indicating a significant improvement in effectiveness. The BPaLMZ treatment also generally causes fewer side effects. The World Health Organization (WHO) has recommended a similar drug combination for other types of TB due to its faster and more successful results. These findings suggest that BPaLMZ could be a strong option for treating TB meningitis. ^{1 2 3 4 6}

Who Is on the Research Team?

David Boulware, MD

Principal Investigator

University of Minnesota

Are You a Good Fit for This Trial?

Adults over 18 with a first episode of definite or probable tuberculosis meningitis (TBM) and intent to treat, living with HIV, weighing more than 35kg. Excluded are those with rifampicin-resistant TB, significant prior TB treatment, certain allergies or medical conditions including severe kidney issues, pregnancy/breastfeeding women, other CNS infections or serious heart/liver diseases.

Inclusion Criteria

Provision of Informed Consent by participant or surrogate

Living with HIV

Weight > 35kg, estimate or measured

Exclusion Criteria

I have TB that is resistant to rifampicin.

I have taken more than 5 doses of TB treatment in the last 2 weeks.

I am allergic or cannot take the study medicine due to health reasons.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either the BPaLMZ regimen or the standard of care RHZE regimen

24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• BPaLMZ Regimen

Trial Overview The study is testing the BPaLMZ regimen against the standard of care (RHZE) for tuberculous meningitis. Participants will be compared in two stages to see if BPaLMZ offers better outcomes than the current treatments used for this condition.

How Is the Trial Designed?

Group I: BPaLMZ Regimen Experimental Treatment 1 Intervention

bedaquiline, pretomanid, linezolid, moxifloxacin, and pyrazinamide (BPaLMZ)

Group II: Standard of Care Regimen Active Control 1 Intervention

rifampicin, isoniazid, pyrazinamide, ethambutol (RHZE) therapy

Who Is Running the Clinical Trial?

University of Minnesota

Lead Sponsor

Trials

1,459

Recruited

1,623,000+

Infectious Diseases Institute

Collaborator

Trials

1

Recruited

510+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12253933/

Bedaquiline, Pretomanid, Linezolid, and Moxifloxacin ... - PMC Unfavourable outcome occurred in 11% in the treatment arm versus 48% in the standard of care arm. There were fewer side effects in the BPaLM ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT07227779

Study Details | NCT07227779 | B-PaLMZ for TB Meningitis This two-stage study will compare consented research participants with tuberculous meningitis receiving BPaLMZ to controls receiving SOC of rifampicin (R), ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S1201971225002875

Can 6-month long regimens become the standardized ... In 2022, the WHO recommended the first ever 6-month regimen for MDR-TB composed of bedaquiline (BdQ), pretomanid (Pa), linezolid (L), and moxifloxacin (M), ...

4. journals.lww.com journals.lww.com/co-infectiousdiseases/fulltext/2025/12000/new_drugs_for_the_management_of_tuberculosis.3.aspx

New drugs for the management of tuberculosis This review summarizes recent and emerging advances in tuberculosis (TB) treatment, focusing on new therapeutics, repurposed agents, and shortened treatment ...

5. tbksp.who.int tbksp.who.int/en/node/2976

1. Treatment of drug-resistant TB using 6-month regimens Much improved treatment success rates with the BPaLM regimen (89%) of 6 months duration compared with the current SoC regimens (52%).

6. ijidonline.com ijidonline.com/article/S1201-9712(25)00287-5/pdf

Journal Pre-proof The Nix-TB trial demonstrated the potential of the BPaL regimen as an effective treatment for highly drug-resistant tuberculosis, although some ...