Teicoplanin for Cystic fibrosis | Staphylococcus aureus infection

Inclusion criteria

• {"criterion_text":"- Male or female patients, aged ≥12 years with a confirmed diagnosis of Cystic Fibrosis and persistent Staphylococcus aureus (including MRSA) infection (≥3 positive culture of Staphylococcus aureus (including MRSA) in sputum within the 24 months prior to enrollment)"}
• {"criterion_text":"- Patients with FEV1 ≥ 50% and ≤ 90% of predicted"}
• {"criterion_text":"- Patients able to understand the nature of the study and willing to comply with the protocol requirements"}
• {"criterion_text":"- Patients who (or if < 18 years of age, whose guardians) have signed written informed consent to participate to the study after benefits and risks have been fully explained"}

Exclusion criteria

• {"criterion_text":"- Patients with chronic Pseudomonas aeruginosa and Bulkholderia cepacia infections will be excluded from the study because it is known that these pathogens cause progressive loss of lung function and requires the administration of inhaled antibiotics. Patients with colonization by others Gram – are instead elegible"}
• {"criterion_text":"- Patients with known episodes of bronchoconstriction after drug inhalation."}
• {"criterion_text":"- Abnormal laboratory findings or other findings or medical history at Screening that, in the Investigator's opinion, would compromise the safety of the subject or the quality of the study data."}
• {"criterion_text":"- Ongoing or prior participation in an investigational drug study within 28 days of the Screening Visit. A washout period of 5 terminal half-lives of the previous investigational study drug, or 28 days, whichever is longer, must elapse before the Screening Visit."}
• {"criterion_text":"- Female patients who are pregnant or breast-feeding or who wish to become pregnant during the period of the clinical study and for one months later."}
• {"criterion_text":"- Female patients of childbearing age (less than 24 months after the last menstrual cycle) who do not use adequate contraception. A woman is considered of childbearing potential (WOCBP), i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy. However in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient."}
• {"criterion_text":"- Patients under treatment with Kaftrio+Kalydeco for less than 6 consecutive months"}
• {"criterion_text":"- Patients with medical history of hemoptysis (> 300 cc in 30 days)"}
• {"criterion_text":"- Patients with decreased liver function (AST or ALT > 3 times higher in comparison to reference values)"}
• {"criterion_text":"- Patients with inability to tolerate inhaled products"}
• {"criterion_text":"- Patients with renal insufficiency (those with eGFR < 15 mL/min/1.73 sqm calculated using the Schwartz formula, which then correspond to CKD V)"}
• {"criterion_text":"- Patients lung transplanted and on the waiting list for lung transplantation"}
• {"criterion_text":"- Patients with known or suspected allergy or hypersensitivity to glycopeptides or other antibiotics or to any of the excipients"}
• {"criterion_text":"- Patients treated with nebulized or systemic vancomycin or teicoplanin within 8 weeks before the study enrollment."}

Primary endpoints

• {"endpoint_text":"- The primary endpoint of the study is the evaluation of safety and tolerability of inhaled teicoplanin. This will be measured as: a) decline from baseline of FEV1 value ≥ 20% after 30 minutes from administration; b) oxygen saturation < 90% after 30 minutes from administration; c) severe coughing; d) chest tightness; e) throat discomfort; f) moderate/severe dyspnea","definition_or_measurement_approach":"Safety and tolerability measured by: a) decline from baseline of FEV1 ≥20% at 30 minutes post-administration; b) oxygen saturation <90% at 30 minutes post-administration; c) severe coughing; d) chest tightness; e) throat discomfort; f) moderate/severe dyspnea."}

Secondary endpoints

• {"endpoint_text":"- Changes in bacterial load of Staphylococcus aureus in sputum as determined by CFU values at baseline (Visit 2) and at Visits 3 (after 1st treatment cycle), Visits 5 (after 2nd treatment cycle) and Visits 6 (after follow-up period), in comparison to baseline","definition_or_measurement_approach":"Bacterial load measured by CFU values in sputum at specified visits (baseline Visit 2; Visit 3 after 1st cycle; Visit 5 after 2nd cycle; Visit 6 after follow-up) compared to baseline."}
• {"endpoint_text":"- Changes in pulmonary function tests as determined by FEV1 at baseline (Visit 2) and at each study visit until end of follow-up period, in comparison to baseline.","definition_or_measurement_approach":"FEV1 measured at baseline (Visit 2) and at each study visit through follow-up compared to baseline."}
• {"endpoint_text":"- Changes in Lung Clearance Index (LCI) measured at baseline (Visit 2) and at each study visit until end of follow-up period, in comparison to baseline","definition_or_measurement_approach":"LCI measured at baseline and at each study visit through follow-up compared to baseline."}
• {"endpoint_text":"- Changes in plethysmography values measured at baseline (Visit 2) and at the end of the treatment (Visit 5)","definition_or_measurement_approach":"Plethysmography values measured at baseline (Visit 2) and at end of treatment (Visit 5) compared to baseline."}
• {"endpoint_text":"- Rate of persistent Staphylococcus aureus infection eradication among the patients being treated with the drug at a dosage of 200 mg/3ml BID for two cycles of 28 days separated by 28 days without treatment.","definition_or_measurement_approach":"Eradication rate determined among patients treated with inhaled teicoplanin 200 mg/3ml BID for two 28-day cycles separated by 28 days off treatment."}

Italy

Earliest CTIS Part Ii Submission Date

04-09-2024

Latest Decision Or Authorization Date

07-10-2024

Processing Time Days

33

Number Of Sites

2

Number Of Participants

12

Primary sponsor

Full Name

Azienda Ospedaliera Universitaria Integrata Verona

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Italy