Phase II study on the safety and efficacy of cysteamine in association with standard tuberculosis therapy for the treatment of patients with pulmonary tuberculosis: a new therapy for tuberculosis directed at the host

Phase II study on the safety and efficacy of cysteamine in association with standard tuberculosis therapy for the treatment of patients with pulmonary tuberculosis: a new therapy for tuberculosis directed at the host - CISTA-TB

Status

Active, not recruiting

Phases

Phase 2

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2019-002514-40-IT

Enrollment

Registered

2021-05-24

Start date

2019-10-31

Completion date

Unknown

Last updated

2024-12-03

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Pulmonary Mycobacterium tuberculosis infection MedDRA version: 20.0 Level: PT Classification code 10037440 Term: Pulmonary tuberculosis System Organ Class: 10021881 - Infections and infestations

Interventions

Trade Name: CYSTAGON - 150 MG 100 CAPSULE FLACONE USO ORALE Product Name: Cystagon Product Code: [-] Pharmaceutical Form: Capsule, hard INN or Proposed INN: 00191501 CAS Number: 60-23-1 Current Sponso

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: • Age between 18 and 65; • Clinical signs and symptoms of pulmonary tuberculosis (new diagnosis) • Abnormal chest x-ray compatible with pulmonary tuberculosis • At least one positive sputum for acid-resistant bacteria (BAAR) (bacterisoscopic examen) [and molecular confirmation for M. tuberculosis by Xpert Mycobacterium tuberculosis (MTB) / rifampicin resistance (RIF) with a cycle threshold (Ct) 50 kg • Karnofsky score of at least 60 • Levels of leukocyte cystine (=65 years) no F.1.3.1 Number of subjects for this age range

Exclusion criteria

Exclusion criteria: • Age> 65 years and <18 years • Use of antiretroviral drugs • Hemoglobin concentration under 10 g / dl • Elevation of creatinine kinase at baseline more than three times the upper limit of normal • Abnormal baseline laboratory values ¿¿(baseline concentration of alanine aminotransferase (ALT) more than three times the upper limit of normal, serum creatinine concentration more than twice the upper limit of normal, total bilirubin serum level greater than twice the upper limit of normal, platelet count <100,000 / mm3, white blood cells (WBC) <2500 (mcL) • Pregnancy or breast-feeding • Silico-Tuberculosis • Previous anti-tuberculosis treatment or use for more than 5 days of anti-tuberculosis drugs in the 3 months prior to enrollment • Concomitant diseases or conditions for which anti-tuberculosis drugs are contraindicated. These include severe liver failure, acute arthritis, peripheral neuropathy • Presence of any physical or psychological condition which, according to the person responsible of the study, makes participation in the study inadvisable • Infection with an isolate known to be resistant to a first drug for tuberculosis, for example rifampicin • Scheduled or current use of cyclosporine, tacrolimus, erythromycin or colchicine • TB with extra-pulmonary localization • Therapy with immunosuppressive drugs and / or NSAIDs and / or cortisone drugs • TB resistant to first and second line drugs • Inability to understand and sign informed consent • Positivity for HIV, HCV, HBV (HBsAg positivity) • Hepatic impairment (Child A-C), Renal failure (creatinine clearance <50 ml / min), heart failure (NYHA III-IV), decompensated diabetes mellitus, neoplasms, ongoing neurological / psychiatric pathology (eg depression, psychotic crisis, suicide attempt), inflammatory bowel diseases or gastric ulcer / duodenal treatment, autoimmune diseases • Abuse of drugs / alcohol • Hypersensitivity to cysteamine or penicillin • Current use of cysteamine • Participation in other Clinical Trials

Design outcomes

Primary

Measure	Time frame
Main Objective: Assess the safety and tolerability of cysteamine in adult patients with bacillifera pulmonary tuberculosis as adjunctive therapy to standard anti-tuberculosis treatment;Secondary Objective: -Evaluate the efficacy of cysteamine through early bactericidal activity (EBA) through the use of culture from sputum at different time points (days -1, 7 and 14); the molecular assay for the assessment of bacterial load (MBLA) will be performed at the same time points as the EBA - Define the immunological and molecular bases of cysteamine activity; - Identify biomarkers useful for the monitoring of therapy in different biological samples (blood, plasma, serum, urine, sputum, saliva) at different time points [day 0, 7, 14, 28, 60, end of therapy (month 6) and month 18].;Primary end point(s): • Treatment acceptability. • Adherence: assumed doses / expected doses of cysteamine. • Treatment tolerance. • Pharmacokinetics of all administered drugs performed on plasma and urine. • Evaluation of serious adverse events (SAEs) and unexpected events • Correlation of possible AEs and SAEs with pharmacokinetic profiles.;Timepoint(s) of evaluation of this end point: • at each study visit --> treatment acceptability. • at each study visit --> adherence: assumed doses / expected doses of cysteamine. • at each study visit --> treatment tolerance. • at each study visit --> pharmacokinetics of all administered drugs performed on plasma and urine. • at each study visit --> evaluation of serious adverse events (SAEs) and unexpected events • at each study visit --> correlation of possible AEs and SAEs with pharmacokinetic profiles.	—

Measure

Time frame

Main Objective: Assess the safety and tolerability of cysteamine in adult patients with bacillifera pulmonary tuberculosis as adjunctive therapy to standard anti-tuberculosis treatment;Secondary Objective: -Evaluate the efficacy of cysteamine through early bactericidal activity (EBA) through the use of culture from sputum at different time points (days -1, 7 and 14); the molecular assay for the assessment of bacterial load (MBLA) will be performed at the same time points as the EBA - Define the immunological and molecular bases of cysteamine activity; - Identify biomarkers useful for the monitoring of therapy in different biological samples (blood, plasma, serum, urine, sputum, saliva) at different time points [day 0, 7, 14, 28, 60, end of therapy (month 6) and month 18].;Primary end point(s): • Treatment acceptability. • Adherence: assumed doses / expected doses of cysteamine. • Treatment tolerance. • Pharmacokinetics of all administered drugs performed on plasma and urine. • Evaluation of serious adverse events (SAEs) and unexpected events • Correlation of possible AEs and SAEs with pharmacokinetic profiles.;Timepoint(s) of evaluation of this end point: • at each study visit --> treatment acceptability. • at each study visit --> adherence: assumed doses / expected doses of cysteamine. • at each study visit --> treatment tolerance. • at each study visit --> pharmacokinetics of all administered drugs performed on plasma and urine. • at each study visit --> evaluation of serious adverse events (SAEs) and unexpected events • at each study visit --> correlation of possible AEs and SAEs with pharmacokinetic profiles.

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Secondary

Measure	Time frame
Secondary end point(s): • Evaluate the efficacy of cysteamine through early bactericidal activity (EBA) through the use of culture from sputum at different time points (day -1, 7 and 14); the molecular assay for the assessment of bacterial load (MBLA) will be performed at the same time points as the EBA.; • Evaluation of biomarkers useful for the monitoring of therapy in different biological samples (blood, plasma, serum, urine, sputum, saliva) at different time points [day 0, 7, 14, 28, 60, end of therapy (month 6)] ( in particular, cytokines / chemokines in plasma, sputum, saliva, urine by Luminex method or Ella will be evaluated • Immunological characterization of cysteamine activity. In particular, cell mononuclear markers, cytokine production and memory profile (CD3, CD4, CD8, CD19, CD45RA, CD27, CCR7 , CD38, CD25, HLA-DR, IFNg, TNFa, IL2) by flow cytometry; these results will be correlated with clinical, microbiological, radiological results.;Timepoint(s) of evaluation of this end point: day -1, 7 and 14 --> evaluate the efficacy of cysteamine through early bactericidal activity (EBA) through the use of culture from sputum at different time points (day -1, 7 and 14); the molecular assay for the assessment of bacterial load (MBLA) will be performed at the same time points as the EBA.; day 0, 7, 14, 28, 60, end of therapy (month 6)]	—

Measure

Time frame

Secondary end point(s): • Evaluate the efficacy of cysteamine through early bactericidal activity (EBA) through the use of culture from sputum at different time points (day -1, 7 and 14); the molecular assay for the assessment of bacterial load (MBLA) will be performed at the same time points as the EBA.; • Evaluation of biomarkers useful for the monitoring of therapy in different biological samples (blood, plasma, serum, urine, sputum, saliva) at different time points [day 0, 7, 14, 28, 60, end of therapy (month 6)] ( in particular, cytokines / chemokines in plasma, sputum, saliva, urine by Luminex method or Ella will be evaluated • Immunological characterization of cysteamine activity. In particular, cell mononuclear markers, cytokine production and memory profile (CD3, CD4, CD8, CD19, CD45RA, CD27, CCR7 , CD38, CD25, HLA-DR, IFNg, TNFa, IL2) by flow cytometry; these results will be correlated with clinical, microbiological, radiological results.;Timepoint(s) of evaluation of this end point: day -1, 7 and 14 --> evaluate the efficacy of cysteamine through early bactericidal activity (EBA) through the use of culture from sputum at different time points (day -1, 7 and 14); the molecular assay for the assessment of bacterial load (MBLA) will be performed at the same time points as the EBA.; day 0, 7, 14, 28, 60, end of therapy (month 6)]

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Countries

Italy

Contacts

Public ContactUO Ricerca Traslazionale

Istituto Nazionale per le Malattie Infettive Lazzaro Spallanzani

delia.goletti@inmi.it065582825

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026