B-PaLMZ for TB Meningitis

A PHASE 2 NOVEL ANTIMICROBIAL COMBINATION THERAPY TO TREAT TUBERCULOUS MENINGITIS

This two-stage study will compare consented research participants with tuberculous meningitis receiving BPaLMZ to controls receiving SOC of rifampicin (R), isoniazid (H), pyrazinamide (Z), and ethambutol (E), known as RHZE.

Study Overview

• Status: Recruiting
• Conditions: HIV; Meningitis; TB - Tuberculosis; Tuberculous Meningitis
• Intervention / Treatment: Drug: BPaLMZ Regimen

• Study Type: Interventional
• Enrollment (Estimated): 312
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: David Boulware, MD; Phone Number: 612-624-9996; Email: coat.trial@gmail.com
• Study Contact Backup: Name: Darlisha Williams, MPH; Phone Number: 612-624-0469; Email: will1223@umn.edu

Study Locations

• Uganda
  • Kampala, Uganda
    • Recruiting
    • Infectious Diseases Institute
    • Contact: Suzan Namombwe, MBChB; Email: snamombwe@idi.co.ug
    • Principal Investigator: David B Meya, MBChB, MMed, PhD
  • Mbarara, Uganda
    • Recruiting
    • Mbarara University of Science and Technology
    • Contact: Conrad Muzoora, MBChB MMed; Phone Number: 256772547175; Email: conradmuzoora@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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
• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BPaLMZ Regimen; bedaquiline, pretomanid, linezolid, moxifloxacin, and pyrazinamide (BPaLMZ)	Drug: BPaLMZ Regimen; bedaquiline, pretomanid, linezolid, moxifloxacin, and pyrazinamide
No Intervention: Standard of Care Regimen; rifampicin, isoniazid, pyrazinamide, ethambutol (RHZE) therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Death		24 Weeks
Hierarchical composite endpoint (survival + functional status)	Hierarchical composite endpoint of survival and modified Rankin score (0-6 scale) assessed by Win Ratio	24 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serious adverse events (SAE)	Incidience of Serious adverse events	28 weeks
Clinical Adverse Events	Clinical Adverse Events, by grade (1-5) associated with TB drug discontinuation, dose reduction, or interruption >3 days	28 weeks
Laboratory abnormalities	Number of participants with grade 3 or 4 abnormal laboratory values, by the Division of AIDS toxicity grading scale	28 weeks
Neuropathy	Incidence of Neuropathy	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)	28 weeks
Change in CSF inflammatory markers	Change in CSF leukocytes from baseline to day 7 and 14 visits.	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	24 weeks
Change in blood inflammatory markers	Change in white blood cell count from baseline to day 7 visit	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.	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.	14 days
Altered Mental Status over time	Number of days with Glasgow Coma Scale score = 15 within the first 10 days	10 days
Additional corticosteroids use	Additional corticosteroids use in TBM survivors (beyond initial use)	24 weeks
Change in CSF glcuose	Change in CSF glcuose from baseline to day 7 to day 14	14 days
Change in serum C-reactive protein	Change in serum C-reactive protein (CRP) from baseline to day 7	7 days

Collaborators and Investigators

• Sponsor: David Boulware
• Collaborators: Radboud University Medical Center; University of Minnesota; Mbarara University of Science and Technology; Brighton & Sussex Medical School; Infectious Diseases Institute, Uganda; Meningitis Foundation
• Investigators: Principal Investigator: David Boulware, MD, University of Minnesota

Study record dates

Study Major Dates

• Study Start (Actual): July 28, 2026
• Primary Completion (Estimated): March 31, 2028
• Study Completion (Estimated): September 30, 2030

Study Registration Dates

• First Submitted: November 11, 2025
• First Submitted That Met QC Criteria: November 11, 2025
• First Posted (Actual): November 13, 2025

Study Record Updates

• Last Update Posted (Actual): September 15, 2026
• Last Update Submitted That Met QC Criteria: September 11, 2026
• Last Verified: September 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Latent Infection; Neuroinflammatory Diseases; Tuberculosis, Extrapulmonary; Central Nervous System Diseases; Nervous System Diseases; Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Central Nervous System Infections; Actinomycetales Infections; Mycobacterium Infections; Meningitis, Bacterial; Central Nervous System Bacterial Infections; Tuberculosis; Tuberculosis, Central Nervous System; Meningitis; Latent Tuberculosis; Tuberculosis, Meningeal
• Other Study ID Numbers: STUDY00024610

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: deidentified dataset
• IPD Sharing Time Frame: At time of publication, as per ICJME
• IPD Sharing Access Criteria: public access
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No