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.

Trial details

Who runs it

National Institute For Infectious Diseases Lazzaro Spallanzani

Trial code

EU 2024-516088-10-00

Record updated

2025. július 17.

Original description

Investigate in an off-label phase II study in adult patients with bacilliferous pulmonary TB, the safety and tolerability of using cysteamine as adjunctive therapy to standard TB treatmentRead full original descriptionShow less

Investigate in an off-label phase II study in adult patients with bacilliferous pulmonary TB, the safety and tolerability of using cysteamine as adjunctive therapy to standard TB treatment

Inclusion: Age between 18 and 65 years; Clinical signs and symptoms of pulmonary tuberculosis (new diagnosis); Abnormal chest radiograph compatible with pulmonary tuberculosis; At least one positive sputum for alcohol-acid-resistant bacteria (BAAR) (bacterisoscopic examination) and molecular confirmation for M. tuberculosis by DNA detection of M. tuberculosis complex with a cycle threshold (Ct) <40, associated with possible genotypic resistance finding to rifampin and isoniazid; Sensitivity to first-line antitubercular drugs by phenotypic pharmacosensitivity test on MGIT liquid medium; Infertility status in females. A woman is considered to be potentially fertile, or fertile, after menarche and until she enters postmenopause, unless she is permanently sterile. Permanent sterilization methods include hysterectomy, bilateral salpingectomy, and bilateral oophorectomy. Postmenopausal status is defined as the absence of menses for 12 months without an alternative medical cause. An elevated follicle-stimulating hormone (FSH) level in the postmenopausal range can be used to confirm postmenopausal status in women who are not using hormonal contraceptives or hormone replacement therapy. However, in the absence of 12 months of amenorrhea, a single FSH measurement is not sufficient. Therefore, for the purposes of this protocol, infertility status in females will be defined as: Premenopausal with: documented bilateral salpingectomy, hysterectomy, documented bilateral oophorectomy. In the post-menopausal phase: with 12 months of spontaneous amenorrhea and confirmation; Body Weight ≥50 kg; Karnofsky score ≥60 %; Ability to provide informed consent; Ability to adhere to follow-up visits; Consent to be hospitalized for 4 weeks; Consent to treatment under direct observation; Consent to adhere to contraception requirements for subjects of childbearing age from 2 weeks prior to enrollment to 18 weeks after experimental drug administration; Consent to perform a pregnancy test prior to administration of the experimental drug for female subjects of childbearing age.

Exclusion: Concomitant diseases or conditions for which anti-tubercular drugs are contraindicated. These include severe liver failure, acute arthritis, peripheral neuropathy; Therapy with immunosuppressant drugs and/or NSAIDs and/or corticosteroids in the 4 weeks prior at enrollment; TB resistant to first- and second-line drugs; Drug/alcohol abuse; use of antiretroviral drugs; Previous anti-tubercular treatment or use for more than 5 days of anti-tubercular drugs in the 3 months prior to enrollment; Presence of any physical or psychological condition that, in the opinion of the principal investigator, makes participation in the study contraindicated; Seropositivity for HIV, HCV, HBV (HBsAg positivity); Hypersensitivity to cysteamine or penicillin; Silico-tuberculosis; Liver failure (Child B-C), renal failure (creatinine clearance < 50 ml/min), heart failure (NYHA III-IV), decompensated diabetes mellitus, neoplasms (those who have had cycles of chemotherapy including biologic drugs and/or radiation therapy in the past 5 years), ongoing neurological/psychiatric pathology (e.g. depression, psychotic break, suicide attempt), chronic inflammatory bowel disease or gastric/duodenal ulcer under treatment, autoimmune disease; Hemoglobin concentration less than 10 g/dl; Increasing of creatinine kinase at baseline more than three times the upper limit of normal; Abnormal laboratory values at baseline (baseline alanine aminotransferase (ALT) concentration more than three times the upper limit of normal, serum creatinine concentration more than twice the upper limit of normal, serum total bilirubin level more than twice the upper limit of normal, platelet count <100,000/mm3, white blood cell (WBC) <2500 (mcL); Age > 65 years and <18 years; Planned or current use of cyclosporine, tacrolimus, erythromycin or colchicine; TB with extra-pulmonary localization; Inability to understand and sign informed consent; Body weight < 50 kg; Current use of cysteamine; Participation in other Clinical Trials; Pregnancy or breastfeeding.

EU CTIS 2024-516088-10-00