An open-label study to evaluate the safety and tolerability of inhaled Teicoplanin in the treatment of Staphylococcus aureus (including mrsa) infections in cystic fibrosis patients

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Azienda Ospedaliera Universitaria Integrata Verona

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

Trial duration

29 Nov 2024 → ongoing

Decision date (initial)

2024-10-07

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Department fund of UOC Fibrosi Cistica - AOUI Verona

External identifiers

EU CT number

2024-517820-21-00

EudraCT number

2023-000005-12

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Therapy

The primary objective of the study is to determine the safety and tolerability of inhaled teicoplanin in patients suffering from cystic fibrosis associated to persistent Staphylococcus aureus (including MRSA) infection treated with the drug at a dosage of 200 mg/3ml BID for two cycles of 28 days separated by 28 days without treatment.

Secondary objectives 5

1. to assess the degree of microbiological improvement following treatment with inhaled teicoplanin at a dosage of 200 mg/3ml BID for two cycles of 28 days separated by 28 days without treatment, measured as reduction of the Staphylococcus aureus CFUs presence in the sputum throughout the study period
2. to assess the effect of the treatment with inhaled teicoplanin on the FEV1 value, in comparison to baseline
3. to assess the effect of the treatment with inhaled teicoplanin on the Lung Clearance Index (LCI) value, in comparison to baseline
4. to assess the effect of the treatment with inhaled teicoplanin on the plethysmography values, in comparison to baseline
5. to evaluate the effect of the treatment with inhaled teicoplanin in eradicating persistent Staphylococcus aureus infection

Conditions and MedDRA coding

cystic fibrosis associated to persistent Staphylococcus aureus (including MRSA) infection

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. 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)
2. Patients with FEV1 ≥ 50% and ≤ 90% of predicted
3. Patients able to understand the nature of the study and willing to comply with the protocol requirements
4. 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 14

1. 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
2. Patients under treatment with Kaftrio+Kalydeco for less than 6 consecutive months
3. Patients with medical history of hemoptysis (> 300 cc in 30 days)
4. Patients with decreased liver function (AST or ALT > 3 times higher in comparison to reference values)
5. Patients with inability to tolerate inhaled products
6. Patients with renal insufficiency (those with eGFR < 15 mL/min/1.73 sqm calculated using the Schwartz formula, which then correspond to CKD V)
7. Patients lung transplanted and on the waiting list for lung transplantation
8. Patients with known or suspected allergy or hypersensitivity to glycopeptides or other antibiotics or to any of the excipients
9. Patients treated with nebulized or systemic vancomycin or teicoplanin within 8 weeks before the study enrollment.
10. Patients with known episodes of bronchoconstriction after drug inhalation.
11. 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.
12. 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.
13. 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.
14. 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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

Secondary endpoints 5

1. 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
2. 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.
3. 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
4. Changes in plethysmography values measured at baseline (Visit 2) and at the end of the treatment (Visit 5)
5. 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.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Azienda Ospedaliera Universitaria Integrata Verona

Sponsor organisation

Azienda Ospedaliera Universitaria Integrata Verona

Address

Piazzale Aristide Stefani 1

City

Verona

Postcode

37126

Country

Italy

Scientific contact point

Organisation

Azienda Ospedaliera Universitaria Integrata Verona

Contact name

Marco Cipolli

Public contact point

Organisation

Azienda Ospedaliera Universitaria Integrata Verona

Contact name

Marco Cipolli

Locations

1 EU/EEA country · 2 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 11 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications