Evaluation of the Safety and Tolerability of Inhaled Teicoplanin in Cystic Fibrosis Patients with Persistent Staphylococcus aureus Infections
- Trial ID
- 2024-517820-21-00
- Protocol
- CRCFC-TEICO.SA.2022
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the **safety** and **tolerability** of inhaled teicoplanin in patients with cystic fibrosis associated with persistent **Staphylococcus aureus** (including MRSA) infection. The treatment involves administering teicoplanin at a dosage of 200 mg/3ml BID for two cycles of 28 days, with each cycle separated by a 28-day period without treatment. This objective is clinically relevant as it aims to ensure that the treatment is safe and well-tolerated in this patient population, which is crucial for the management of infections in cystic fibrosis.
Secondary objectives include:
- Assessing the degree of microbiological improvement by measuring the reduction of Staphylococcus aureus CFUs in the sputum throughout the study period.
- Evaluating the effect of the treatment on the FEV1 value compared to baseline.
- Assessing the impact on the Lung Clearance Index (LCI) value in comparison to baseline.
- Evaluating changes in plethysmography values relative to baseline.
- Determining the effect of the treatment in eradicating persistent Staphylococcus aureus infection.
Participants
The clinical trial involves a study population comprising **male and female** patients aged 12 years and older, diagnosed with **cystic fibrosis** associated with persistent **Staphylococcus aureus** (including MRSA) infection. The sponsor has not provided the total number of participants. Participants were selected based on specific criteria, including having at least three positive cultures of **Staphylococcus aureus** in sputum within the 24 months prior to enrollment and a forced expiratory volume (FEV1) between 50% and 90% of the predicted value. The trial includes individuals who are able to understand the study's nature and comply with protocol requirements, with informed consent obtained from participants or their guardians if under 18 years of age. The study population is considered vulnerable, and no specific lifestyle considerations such as diet or physical activity are highlighted in the trial data.
Plans and Procedures
The clinical trial is designed to evaluate the **safety** and tolerability of inhaled **teicoplanin** in patients with **cystic fibrosis** associated with persistent **Staphylococcus aureus** (including MRSA) infection. This is an open-label, phase IV study, where participants will receive the investigational product, Teicoplanin Sandoz 200 mg, administered via inhalation. The trial will span an estimated duration from September 2024 to September 2025, with participant involvement lasting up to 56 days of active treatment, divided into two cycles of 28 days each, separated by a 28-day period without treatment.
Participants will undergo a series of study visits, beginning with a screening visit to confirm eligibility based on inclusion criteria such as age (≥12 years), confirmed diagnosis of cystic fibrosis, and persistent Staphylococcus aureus infection. Baseline assessments will be conducted at Visit 2, including pulmonary function tests and bacterial load measurements. Subsequent visits will occur after each treatment cycle (Visits 3 and 5) and after the follow-up period (Visit 6), to monitor changes in bacterial load, pulmonary function, and other safety parameters.
The primary endpoint focuses on the safety and tolerability of inhaled teicoplanin, assessed by monitoring adverse events such as a decline in FEV1, oxygen saturation levels, and respiratory symptoms. Secondary endpoints include changes in bacterial load, pulmonary function tests, and the rate of infection eradication. Participants may be withdrawn from the study if they experience significant adverse events or if they fail to comply with the study protocol. The trial aims to provide valuable data on the use of inhaled teicoplanin in this patient population, contributing to the understanding of its safety profile and therapeutic potential.
Treatment
The clinical trial involves the administration of **Teicoplanin**, marketed as Teicoplanina Sandoz 200 mg, which is a **solution for injection/infusion**. The active substance, teicoplanin, is a mixture used primarily for its antibacterial properties. In this study, the medication is administered via **inhalation** to evaluate its safety and tolerability in patients with cystic fibrosis suffering from persistent **Staphylococcus aureus** infections, including methicillin-resistant Staphylococcus aureus (MRSA). The dosage regimen consists of 200 mg of teicoplanin dissolved in 3 ml, administered twice daily (BID) for two cycles of 28 days each, with a 28-day treatment-free interval between cycles. The maximum daily dose is 400 mg, and the total treatment period spans 56 days.
No non-experimental treatments, such as standard-of-care therapy, placebo, or comparator treatments, are specified in the trial documentation. The study focuses solely on the experimental use of inhaled teicoplanin. Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the prescribed regimen. The trial is designed to assess the primary objective of determining the safety and tolerability of the inhaled formulation in the specified patient population.
Efficacy
The efficacy of inhaled **teicoplanin** in the treatment of persistent **Staphylococcus aureus** infections, including MRSA, in patients with cystic fibrosis will be assessed through several primary and secondary endpoints. The primary endpoint focuses on the safety and tolerability of the treatment, which will be evaluated by monitoring specific adverse events such as a decline in FEV1 value by 20% or more, oxygen saturation below 90%, severe coughing, chest tightness, throat discomfort, and moderate to severe dyspnea, all measured 30 minutes post-administration.
Secondary endpoints will include changes in the bacterial load of **Staphylococcus aureus** in sputum, assessed by CFU values at baseline and subsequent visits, as well as changes in pulmonary function tests, specifically FEV1, at each study visit compared to baseline. Additionally, changes in the Lung Clearance Index (LCI) and plethysmography values will be measured at baseline and at the end of the treatment period. The rate of eradication of persistent **Staphylococcus aureus** infection will also be evaluated among patients receiving the drug at a dosage of 200 mg/3ml BID for two cycles of 28 days, separated by a 28-day period without treatment.
Inclusion and Exclusion Criteria
Inclusion Criteria
- 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)
- Patients with FEV1 ≥ 50% and ≤ 90% of predicted
- Patients able to understand the nature of the study and willing to comply with the protocol requirements
- 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
- 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
- Patients under treatment with Kaftrio+Kalydeco for less than 6 consecutive months
- Patients with medical history of hemoptysis (> 300 cc in 30 days)
- Patients with decreased liver function (AST or ALT > 3 times higher in comparison to reference values)
- Patients with inability to tolerate inhaled products
- Patients with renal insufficiency (those with eGFR < 15 mL/min/1.73 sqm calculated using the Schwartz formula, which then correspond to CKD V)
- Patients lung transplanted and on the waiting list for lung transplantation
- Patients with known or suspected allergy or hypersensitivity to glycopeptides or other antibiotics or to any of the excipients
- Patients treated with nebulized or systemic vancomycin or teicoplanin within 8 weeks before the study enrollment.
- Patients with known episodes of bronchoconstriction after drug inhalation.
- 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.
- 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.
- 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.
- 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.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Italy | Recruiting | 16 Sept 2024 | 12 |
Sites & Investigators
Research sites
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Teicoplanina Sandoz 200 mg polvere e solvente per soluzione iniettabile o infusione o soluzione orale | Test | POLVERE E SOLVENTE PER SOLUZIONE INIETTABILE O INFUSIONE O SOLUZIONE ORALE | INHALATION USE | 400 | 56 | PRD9290203 |