LOS ANGELES, Dec. 07, 2023 (GLOBE NEWSWIRE) — ACTG, a global clinical trials network focused on HIV and other infectious diseases, today announced the opening of the IMAGINE-TBM study (Improved Management with Antimicrobial AGents Isoniazid rifampiciN LinEzolid for TBM, also known as A5384). IMAGINE-TBM is a phase 2, randomized, open-label trial comparing a six-month regimen of high-dose rifampicin, high-dose isoniazid, linezolid, and pyrazinamide to the nine-month standard-of-care regimen for the treatment of tuberculous meningitis.
Tuberculous meningitis is a life-threatening infectious disease that causes inflammation of the membranes that surround the brain and spinal cord. It is the most severe form of tuberculosis and is universally fatal when untreated. Even with standard-of-care treatment, outcomes are poor, with high rates of mortality and chronic disability among those who survive. While the global burden of tuberculous meningitis is unclear (due in large part to limited diagnostics), it is estimated to affect at least 100,000 people worldwide each year.
“ACTG is especially excited about IMAGINE-TBM because it is an important step in addressing the paucity of data evaluating the best treatment approach for this devastating illness,” said ACTG Chair Judith Currier, M.D., M.Sc., University of California, Los Angeles. “ACTG has designed this study with investigators from around the globe with the goal of evaluating the potential benefit of the new regimen in diverse settings.”
This multi-center trial will enroll 330 participants aged 15 years and older who have definite, probable, or possible tuberculous meningitis, including people living with and without HIV. Participants will be randomized in equal proportions to receive either the six-month regimen being studied or the nine-month standard of care:
- Those in the six-month regimen arm will receive rifampicin 35 mg/kg, isoniazid 10-15 mg/kg, linezolid 1200 mg, and pyrazinamide 25 mg/kg for eight weeks followed by rifampicin 35 mg/kg and isoniazid 10 mg/kg for 16 weeks (for a total of 24 weeks of study treatment)
- Those in the nine-month standard-of-care regimen arm will receive rifampicin 10 mg/kg, isoniazid 5 mg/kg, ethambutol 20 mg/kg, and pyrazinamide 25 mg/kg for eight weeks, followed by rifampicin 10 mg/kg and isoniazid 5 mg/kg for 28 weeks (for a total of 36 weeks of study treatment). Up to 15 mg/kg or a maximum of 900 mg daily of oral rifampicin will be permitted at the clinician’s discretion.
“IMAGINE-TBM is ACTG’s first tuberculous meningitis protocol and will take place in locations around the world that have a high tuberculosis burden,” said IMAGINE-TBM protocol Co-Chair Felicia Chow, M.D., M.A.S., University of California, San Francisco. “IMAGINE-TBM is a tremendous opportunity to leverage ACTG’s diverse international sites to test a novel intervention for this devastating form of TB.”
IMAGINE-TB will take place at 17 sites in Peru, Tanzania, Thailand, Vietnam, Mexico, Philippines, India, Brazil, Zimbabwe, Kenya, Malawi, and South Africa. It is sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (which also funds ACTG) under award numbers UM1 AI068636, UM1 AI107716, and UM1 AI068634.
“Our hope is that this regimen will result in improved outcomes among individuals compared to the current standard of care, while significantly decreasing the required length of treatment,” said IMAGINE-TBM protocol Co-Chair Vidya Mave, M.D., M.P.H., Byramjee Jeejeebhoy Government Medical College-Johns Hopkins University Clinical Research Site and Johns Hopkins Center for Infectious Diseases in India. “One of the top priorities for tuberculous meningitis research is optimizing treatment, which could have a profound impact on a population who has historically experienced abysmal outcomes.”
IMAGINE-TBM is led by Drs. Chow and Mave and Kelly Dooley, M.D., Ph.D., Vanderbilt University (Vice-Chair). ACTG is led by Dr. Currier and Joseph J. Eron, M.D., University of North Carolina (ACTG Vice-Chair).
For more information about IMAGINE-TBM, please visit clinicaltrials.gov.
ACTG is the world’s largest and longest running clinical trials network focused on HIV and other infectious diseases and the people living with them. It is funded by NIAID and collaborating NIH Institutes. Founded in 1987, ACTG conducts research to improve the management of HIV and its comorbidities; develop a cure for HIV; and innovate treatments for tuberculosis, hepatitis B, and emerging infectious diseases. It comprises thousands of dedicated researchers, staff, and community members who are pursuing research into novel treatments and cures for infectious diseases at hundreds of locations across four continents, with the ultimate goal of advancing science that meaningfully impacts the lives of the people we serve.
Disclaimer: This content is solely the responsibility of ACTG and does not necessarily represent the official views of the NIH.
Jenna Conley, ACTG