NCT05590455

Tnf Inhibitors to Reduce Mortality in HIV-1 Infected PAtients With Tuberculosis meNIngitis

ANRS 12404 TIMPANI: Tnf Inhibitors to Reduce Mortality in HIV-1 Infected PAtients With Tuberculosis meNIngitis: a Phase II, Multicenter, Randomized Clinical Trial

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 130 (estimated)
• Sponsor: ANRS, Emerging Infectious Diseases · Other Government
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Randomized phase II clinical trial which aims to assess the impact on 3-month mortality and safety of adding adalimumab to standard treatment (anti-tuberculosis drugs and corticosteroids) in HIV patients with tuberculosis meningitis in 3 countries (Brazil, Mozambique, and Zambia).

Detailed description

Phase II multicenter, open-label, randomized, proof of concept, comparative trial with a large alpha (type 1 error rate) to evaluate the impact on 3-month mortality of adding the tumor necrosis factor inhibitor adalimumab to the standard treatment with antituberculosis drugs and high-dose steroids in HIV-infected adults diagnosed with tuberculosis meningitis (TBM) in 3 countries (Brazil, Mozambique, and Zambia). All HIV1-infected patients diagnosed with TBM will be started on standard TB therapy for the duration recommended by national guidelines (2 months intensive phase and 7 months maintenance phase) and high-dose dexamethasone up to 4 weeks. As soon as possible during the first 3 days of the standard TBM treatment that includes antituberculosis treatment and high-dose steroids, consenting patients will be randomized to standard treatment alone or standard treatment + adalimumab. Randomization will be stratified on country and initial severity using the British Medical Research Council (MRC) score. Adalimumab arm: * Standard TBM treatment as described above * Adalimumab 40 mg: one sub-cutaneous injection, every 2 weeks for 10 weeks (total 6 injections), started as soon as possible during the first 3 days of antituberculosis treatment and high-dose steroids As World Health Organization and national guidelines for early antiretroviral therapy (ART) introduction in patients with TBM advise caution, ART will be started after 4 weeks of TB treatment in both arms if patients are clinically improved (but no later than 8 weeks of anti-TB treatment). An interim analysis will be performed after 20 patients have been followed up for 3 months in adalimumab arm. This interim analysis will monitor the safety of adding TNF-inhibitor adalimumab.

Conditions

• Tuberculous Meningitis
• HIV I Infection

Interventions

Type	Name	Description
DRUG	Adalimumab Injection	one sub-cutaneous injection, every 2 weeks for 10 weeks (total 6 injections), started as soon as possible during the first 3 days of antituberculosis treatment and high-dose steroids

Timeline

• Start date: 2023-04-11
• Primary completion: 2027-06-01
• Completion: 2027-12-01
• First posted: 2022-10-21
• Last updated: 2025-12-15

Locations

3 sites across 3 countries: Brazil, Mozambique, Zambia