Tuberculous MeningitisPhase 2TIMPANINCT05590455
Tnf Inhibitors to Reduce Mortality in HIV-1 Infected PAtients With Tuberculosis meNIngitis
A Phase 2 study testing Adalimumab Injection in people with Tuberculous Meningitis and HIV I Infection, run by ANRS, Emerging Infectious Diseases at 3 sites in 3 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Tuberculous Meningitis, HIV I Infection
- What is being tested?
- Adalimumab Injection
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 130 participants
- Where
- 3 sitesin 3 countries
- Study dates
- 11 Apr 2023to Dec 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 14Show fewer
- 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
- Subjects participating in another clinical trial evaluating therapies and including an exclusion period that is still in force during the screening phase
- Person under guardianship, or deprived of freedom by a judicial or administrative decision
Trial locations and contacts
3 sites in 3 countries. Contact the study team or a site near you to ask about taking part.
Olivier MARCY, MD PhD contact
3 sites in 3 countries
Brazil1 site, 1 recruiting
- Recruiting
Laboratory of clinical research on STD/AIDS - IPEC/FIOCRUZ
Rio de Janeiro, 21040-900
Sandra WAGNER, + 55 21 38 65 96 23, dra.wagner@gmail.com
Beatriz GRINSZTEJN
Mozambique1 site, 1 recruiting
- Not yet recruiting
Instituto Nacional de Saude
Maputo
Marcia CHILUVANE, marcia.chiluvane@ins.gov.mz
Celso KHOSA
Zambia1 site, 1 recruiting
- Not yet recruiting
Adult Infectious Diseases Centre, University Teaching Hospital
Lusaka
Christabel Phiri, chigweyassin@gmail.com
Seke Muzazu, sekemuzazu@gmail.com
About this study
Official title: ANRS 12404 TIMPANI: Tnf Inhibitors to Reduce Mortality in HIV-1 Infected PAtients With Tuberculosis meNIngitis: a Phase II, Multicenter, Randomized Clinical Trial
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).
Read the 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
- Being tested
- Adalimumab Injection
- Medical subject headings
- Tuberculosis, Meningeal
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Adalimumab InjectionDrug
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 group | Role | What they receive |
|---|---|---|
| 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 Receives: Drug: Adalimumab Injection |
| Control arm | No intervention | - Standard TBM |
What is being measured
The primary outcome is the main question the study is designed to answer.
3-month all-cause mortality
Measured: 3 months
Secondary outcomes (18)
3-month incidence of severe/life threatening bacterial infections and opportunistic infections
Measured: 3 months
3-month incidence of grade 3 and 4 adverse reactions and those leading to ART or anti tuberculosis treatment (ATT) interruption
Measured: 3 months
3-month incidence of all grade 3 and 4 adverse events
Measured: 3 months
9-month and 12-month all-cause mortality
Measured: 9 months and 12 months
9-month disability free survival (using Rankin score)
MODIFIED RANKIN SCORE (MRS) 0: No symptoms at all
- No significant disability despite symptoms; able to carry out all usual duties and activities
- Slight disability; unable to carry out all previous activities, but able to look after own affairs without assistance
- Moderate disability; requiring some help, but able to walk without assistance
- Moderately severe disability; unable to walk without assistance and unable to attend to own bodily needs without assistance
- Severe disability; bedridden, incontinent and requiring constant nursing care and attention
- Dead
Measured: 9 months
3-month and 9-month incidence of all grade infectious diseases and opportunistic infections
Measured: 3 months and 9 months
9-month neurological disability score (Rankin score)
MODIFIED RANKIN SCORE (MRS) 0: No symptoms at all
- No significant disability despite symptoms; able to carry out all usual duties and activities
- Slight disability; unable to carry out all previous activities, but able to look after own affairs without assistance
- Moderate disability; requiring some help, but able to walk without assistance
- Moderately severe disability; unable to walk without assistance and unable to attend to own bodily needs without assistance
- Severe disability; bedridden, incontinent and requiring constant nursing care and attention
- Dead
Measured: 9 months
Time to and severity of TB-associated paradoxical immune reconstitution inflammatory syndrome (IRIS) between D0 and 9 months
Measured: up to 9 months
Time to discharge
Measured: up to 9 months
Cerebrospinal fluid (CSF) pleocytosis/protein/glucose levels at W0, W1 and W4
Measured: week 0, week1 and week4
CSF mycobacterial cultures negativation (culture conversion), time to culture positivity and cycle threshold (GeneXpert Mycobacterium tuberculosis/Rifampicin Ultra) at W1, W4,
Measured: week1 and week4
Proportion of patients with HIV-1 RNA<50 copies/mL at 9 months
Measured: 9 months
CD4 counts at 9 months (and gain from baseline)
Measured: 9 months
Inflammatory biomarkers and cytokines profiles in CSF at W0, W1, W4
Measured: week 0, week1 and week4
Inflammatory biomarkers in blood at W0, W4, W10, M6 and M9
Measured: week 0, week4, week10, 6 months and 9 months
Cytokines profiles in blood at W0, W4, W10, M6 and M9
Measured: week 0, week4, week10, 6 months and 9 months
Proportion of participants with possible, probable or definite TBM diagnosis at pre-inclusion according to Marais score
Evaluation of TBM diagnosis and differential diagnoses in all pre-included participants: Proportion of participants with possible, probable or definite TBM diagnosis at pre-inclusion according to Marais score
Measured: Pre-inclusion
Proportion of participants with other CNS disease (opportunistic infections or other neurological conditions)
Evaluation of TBM diagnosis and differential diagnoses in all pre-included participants: Proportion of participants with other CNS disease (opportunistic infections or other neurological conditions)
Measured: Pre-inclusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Oct 2022
- Study start11 Apr 2023
- Primary completionJun 2027 (estimated)
- Study completionDec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Tuberculous MeningitisStudies of the same condition, open and under way.
- More trials run by ANRS, Emerging Infectious DiseasesThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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
- Masking
- None (open label)
- Enrolment
- 130 participants (estimated)
Sponsor and investigators
- Lead sponsor
- ANRS, Emerging Infectious Diseases
- Sponsor type
- Other government
- Responsible party
- Sponsor
- Investigators
- Nathalie DE CASTRO, MD, Principal investigator, AP-HP, Hôpital Saint-LouisCelso KHOSA, MD, Principal investigator, Instituto Nacional de Saúde, Mozambique
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05590455
- Sponsor's protocol ID
- ANRS 12404 TIMPANI
- Acronym
- TIMPANI
- Status last verified
- Dec 2025
- First submitted
- 23 Nov 2021
- Last updated
- 15 Dec 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 15 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- ANRS 12404 TIMPANI: Tnf Inhibitors to Reduce Mortality in HIV-1 Infected PAtients With Tuberculosis meNIngitis: a Phase II, Multicenter, Randomized Clinical Trial
- ClinicalTrials.gov ID
- NCT05590455
- Acronym / sponsor ID
- TIMPANI / ANRS 12404 TIMPANI
- Conditions
- Tuberculous Meningitis, HIV I Infection
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 130 participants (estimated)
- Lead sponsor
- ANRS, Emerging Infectious DiseasesOther government
- Study start
- 11 Apr 2023 (actual)
- Primary completion
- Jun 2027 (estimated)
- Study completion
- Dec 2027 (estimated)
- First posted
- 21 Oct 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- 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
| Arm | Type | Receives |
|---|---|---|
| Adalimumab arm | Experimental | Drug: Adalimumab Injection* 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 |
| Control arm | No intervention | –- Standard TBM |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (14 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Adalimumab Injectionone 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 arm |
Primary outcome
3-month all-cause mortality
Time frame: 3 months
18 secondary outcomes
3-month incidence of severe/life threatening bacterial infections and opportunistic infections
Time frame: 3 months
3-month incidence of grade 3 and 4 adverse reactions and those leading to ART or anti tuberculosis treatment (ATT) interruption
Time frame: 3 months
3-month incidence of all grade 3 and 4 adverse events
Time frame: 3 months
9-month and 12-month all-cause mortality
Time frame: 9 months and 12 months
9-month disability free survival (using Rankin score)
Time frame: 9 months
3-month and 9-month incidence of all grade infectious diseases and opportunistic infections
Time frame: 3 months and 9 months
9-month neurological disability score (Rankin score)
Time frame: 9 months
Time to and severity of TB-associated paradoxical immune reconstitution inflammatory syndrome (IRIS) between D0 and 9 months
Time frame: up to 9 months
Time to discharge
Time frame: up to 9 months
Cerebrospinal fluid (CSF) pleocytosis/protein/glucose levels at W0, W1 and W4
Time frame: week 0, week1 and week4
CSF mycobacterial cultures negativation (culture conversion), time to culture positivity and cycle threshold (GeneXpert Mycobacterium tuberculosis/Rifampicin Ultra) at W1, W4,
Time frame: week1 and week4
Proportion of patients with HIV-1 RNA<50 copies/mL at 9 months
Time frame: 9 months
CD4 counts at 9 months (and gain from baseline)
Time frame: 9 months
Inflammatory biomarkers and cytokines profiles in CSF at W0, W1, W4
Time frame: week 0, week1 and week4
Inflammatory biomarkers in blood at W0, W4, W10, M6 and M9
Time frame: week 0, week4, week10, 6 months and 9 months
Cytokines profiles in blood at W0, W4, W10, M6 and M9
Time frame: week 0, week4, week10, 6 months and 9 months
Proportion of participants with possible, probable or definite TBM diagnosis at pre-inclusion according to Marais score
Time frame: Pre-inclusion
Proportion of participants with other CNS disease (opportunistic infections or other neurological conditions)
Time frame: Pre-inclusion
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Dec 2025.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Olivier MARCY, MD PhD contact
Nathalie DE CASTRO, MD principal investigator
AP-HP, Hôpital Saint-Louis
Celso KHOSA, MD principal investigator
Instituto Nacional de Saúde, Mozambique
3 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Adalimumab Injection in people with Tuberculous Meningitis and HIV I Infection, run by ANRS, Emerging Infectious Diseases at 3 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 15 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Brazil, Mozambique, Zambia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Vanessa MACHAULT, PhD (+335 57 57 57 63, vanessa.machault@u-bordeaux.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
3-month all-cause mortality (time frame: 3 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Dec 2025.