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

NCT05590455 | Recruiting Phase 2 DMC

• 1 other identifier: ANRS 12404 TIMPANI
• Study Type: interventional
• Target: 130
• Locations: 3 countries
• Sites: 3

Brief 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).

Conditions

Tuberculous Meningitis; HIV I Infection

Outcome Measures

Primary Outcomes (1)

• 3-month all-cause mortality

  3 months

Secondary Outcomes (18)

• 3-month incidence of severe/life threatening bacterial infections and opportunistic infections

  3 months

• 3-month incidence of grade 3 and 4 adverse reactions and those leading to ART or anti tuberculosis treatment (ATT) interruption

  3 months

• 3-month incidence of all grade 3 and 4 adverse events

  3 months

• 9-month and 12-month all-cause mortality

  9 months and 12 months

• 9-month disability free survival (using Rankin score)

  9 months

Study Arms (2)

Adalimumab arm

EXPERIMENTAL

* Standard TBM treatment * 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

Drug: Adalimumab Injection

Control arm

NO INTERVENTION

\- Standard TBM

Interventions

Adalimumab Injection DRUG

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

Adalimumab arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years
• HIV-1 infection
• Definite or probable tuberculosis meningitis
• Standard tuberculosis meningitis treatment ≤3 days: anti TB drugs at standard doses and high-dose dexamethasone as per WHO guidelines
• Signed informed consent form by patient or relative.

You may not qualify if:

• Other concomitant neurological infection, i.e. toxoplasmosis, cryptococcosis, progressive multifocal leukoencephalopathy, bacterial meningitis, neuro-syphilis
• Asymptomatic positive cryptococcal antigen in serum
• HBsAg positive or anti hepatitis C virus antibodies positive
• Alanine transaminase (ALT)\>5 ULN
• Rifampicin-resistant TB detected by GeneXpert MTB/RIF Ultra
• History of previous TB treatment in patients with GeneXpert MTB/RIF Ultra negative or unavailable
• Current use of drugs contraindicated with study drugs and that cannot be safely stopped
• Allergy to study drugs or any of their components
• Uncontrolled opportunistic infection
• Moderate to severe cardiac insufficiency (NYHA classes III / IV)
• Any condition which might, in the investigator's opinion, compromise the safety of treatment and/or patient's adherence to study procedures
• For women of childbearing age: 1) Pregnancy or breastfeeding; 2) Refusal to use effective contraception to be discussed with the investigator
• Person under guardianship, or deprived of freedom by a judicial or administrative decision

Sponsors & Collaborators

• ANRS, Emerging Infectious Diseases: lead

Study Sites (3)

Laboratory of clinical research on STD/AIDS - IPEC/FIOCRUZ

Rio de Janeiro, 21040-900, Brazil

RECRUITING

Instituto Nacional de Saude

Maputo, Mozambique

NOT YET RECRUITING

Adult Infectious Diseases Centre, University Teaching Hospital

Lusaka, Zambia

NOT YET RECRUITING

MeSH Terms

Conditions

Tuberculosis, Meningeal

Interventions

Adalimumab

Condition Hierarchy (Ancestors)

Meningitis, Bacterial; Central Nervous System Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Tuberculosis, Central Nervous System; Tuberculosis, Extrapulmonary; Tuberculosis; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Central Nervous System Infections; Central Nervous System Diseases; Nervous System Diseases; Meningitis; Neuroinflammatory Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Nathalie DE CASTRO, MD

  AP-HP, Hôpital Saint-Louis

  PRINCIPAL INVESTIGATOR

• Celso KHOSA, MD

  Instituto Nacional de Saúde, Mozambique

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Vanessa MACHAULT, PhD

CONTACT

+335 57 57 57 63; vanessa.machault@u-bordeaux.fr

Olivier MARCY, MD PhD

CONTACT

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Model Details: Phase II multicenter, open-label, randomized, proof of concept, comparative trial with a large alpha (type 1 error rate). 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

Study Record Dates

• First Submitted: November 23, 2021
• First Posted: October 21, 2022
• Study Start: April 11, 2023
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: December 15, 2025

Record last verified: 2025-12

Locations

MO (1); ZA (1); BR (1)