Ceftaroline for Cystic Fibrosis

Age: < 65

Sex: Any

Trial Phase: Phase 4

Sponsor: Children's Hospital Medical Center, Cincinnati

Must be taking: Ceftaroline

Disqualifiers: Age, Weight, Liver function, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 12 hours

24 Participants Needed

Trial Summary

What is the purpose of this trial?

This is an open-label, single center, prospective study of patients with a diagnosis of cystic fibrosis (CF) and a history of methicillin-resistant Staphylococcus aureus (MRSA), also known as oxacillin-resistant Staphylococcus aureus (ORSA), being treated with intravenous ceftaroline. Patients will have intravenous ceftaroline dosed according to current recommendations based upon its approved usage in pediatric patients for community acquired pneumonia. The investigators will analyze pharmacokinetic (PK) and pharmacodynamic (PD) data using serum concentrations of ceftaroline measured at various time-points following infusion of ceftaroline to develop PK/PD guided dosing strategies of ceftaroline in pediatric CF patients that would be tailored to account for bacterial susceptibility and disease progression.

Do I need to stop my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug Ceftaroline for treating cystic fibrosis?

Ceftaroline has shown potential as a treatment for lung infections in cystic fibrosis patients, particularly against methicillin-resistant Staphylococcus aureus (MRSA), as seen in a pediatric case and studies comparing it to vancomycin, a common treatment for these infections. ^{1 2 3 4 5}

Is Ceftaroline safe for use in humans?

Ceftaroline, also known as Teflaro, is generally considered safe for humans and has been approved by the FDA for treating certain bacterial infections in adults and children. It has a favorable tolerability profile, but there is limited safety data for very young children and those with complex medical conditions. ^{1 2 6 7 8}

How does the drug Ceftaroline differ from other treatments for cystic fibrosis?

Ceftaroline is an antibiotic that is typically used to treat bacterial infections like pneumonia and skin infections, which makes it different from other cystic fibrosis treatments that focus on correcting the underlying genetic defect, such as the triple-combination therapy elexacaftor/tezacaftor/ivacaftor. This makes Ceftaroline potentially useful for treating bacterial infections in cystic fibrosis patients, rather than addressing the genetic cause of the disease. ^{9 10 11 12 13}

Research Team

Alexander Vinks, PhD

Principal Investigator

Children's Hospital Medical Center, Cincinnati

Eligibility Criteria

This trial is for children and teens with cystic fibrosis who have had infections caused by a tough-to-treat bacteria called MRSA. They must be in the hospital, weigh at least 15 kg, and their liver tests need to be within certain limits. The study excludes very young kids under 2 years old, adults over 22, those with severe liver issues or low platelets, patients without confirmed CF diagnosis, and non-English speaking families.

Inclusion Criteria

I am currently hospitalized.

My doctor has decided to treat me with intravenous ceftaroline.

I have been diagnosed with Cystic Fibrosis according to the foundation's guidelines.

Exclusion Criteria

Your liver enzymes (AST or ALT) are more than 5 times the normal level.

I am under 2 years old.

Your platelet count is less than 50,000.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive intravenous ceftaroline dosed according to current recommendations for community acquired pneumonia in pediatric patients

12 hours

Single visit

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of pulmonary exacerbations and FEV1 percentage change

4 weeks

Treatment Details

Interventions

• Ceftaroline

Trial Overview The study is testing how the drug Ceftaroline works in the bodies of kids and teens with cystic fibrosis when given through an IV. It looks at how much of the drug gets into the bloodstream and how it fights bacteria. This will help figure out the best doses that match up with disease severity and bacterial resistance.

Participant Groups

Group I: PK/PD Experimental Treatment 1 Intervention

Open-label prospective study with participants receiving treating physician-approved intravenous ceftaroline, dosed according to current recommendations. Blood samples collected at baseline, 1 hour, 1.5 hours, 3 hours, and 6 hours after infusion.

Ceftaroline is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Teflaro for:

• Community-acquired bacterial pneumonia
• Acute bacterial skin and skin structure infections

Approved in European Union as Zinforo for:

• Complicated skin and soft tissue infections
• Community-acquired pneumonia

Approved in Canada as Teflaro for:

• Community-acquired pneumonia
• Acute bacterial skin and skin structure infections

Who Is Running the Clinical Trial?

Children's Hospital Medical Center, Cincinnati

Lead Sponsor

Trials

844

Recruited

6,566,000+

Findings from Research

Elexacaftor-tezacaftor-ivacaftor is a newly approved triple-combination therapy for cystic fibrosis that significantly improves lung function, quality of life, and reduces exacerbations in patients aged 12 and older with at least one F508del mutation in the CFTR gene, surpassing existing treatments.

While the therapy shows promising efficacy, common side effects include rash and headache, and liver function monitoring is advised; however, about 10% of the cystic fibrosis population remains ineligible for this or any CFTR modulation therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Elexacaftor-Tezacaftor-Ivacaftor: The First Triple-Combination Cystic Fibrosis Transmembrane Conductance Regulator Modulating Therapy. Ridley, K., Condren, M.[2020]

The combination therapy of elexacaftor, ivacaftor, and tezacaftor (Trikafta™) has shown significant improvements in lung function and quality of life for cystic fibrosis patients with the F508del mutation, based on multinational phase II and III studies.

In October 2019, this treatment was approved by the US FDA for patients aged 12 and older with at least one F508del mutation, marking a major advancement in cystic fibrosis therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Elexacaftor/Ivacaftor/Tezacaftor: First Approval. Hoy, SM.[2020]

In a review of safety data from 14 clinical trials involving 1,711 participants, the rates of depression-related adverse events in patients with cystic fibrosis treated with elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) were similar to those in the placebo group, indicating no increased risk associated with the treatment.

Postmarketing data from 61,499 patients showed low exposure-adjusted rates of depression-related events, and patterns of depression prevalence did not change after starting ELX/TEZ/IVA, suggesting that any reported depression symptoms are consistent with the background rates in the cystic fibrosis population rather than being caused by the medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Elexacaftor/Tezacaftor/Ivacaftor Treatment and Depression-related Events. Ramsey, B., Correll, CU., DeMaso, DR., et al.[2023]

References

1. United States pubmed.ncbi.nlm.nih.gov

Ceftaroline Fosamil for Methicillin-Resistant Staphylococcus aureus Pulmonary Exacerbation in a Pediatric Cystic Fibrosis Patient. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Pharmacokinetic and Pharmacodynamic Analyses of Ceftaroline in Adults with Cystic Fibrosis. [2023]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Ceftaroline versus vancomycin for treatment of acute pulmonary exacerbations of cystic fibrosis in adults. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Ceftaroline Fosamil for the Treatment of Staphylococcus aureus Bacteremia Secondary to Acute Bacterial Skin and Skin Structure Infections or Community-Acquired Bacterial Pneumonia. [2020]

5. United States pubmed.ncbi.nlm.nih.gov

High incidence of discontinuations due to adverse events in patients treated with ceftaroline. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Ceftaroline fosamil: a novel broad-spectrum cephalosporin with activity against methicillin-resistant Staphylococcus aureus. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Ceftaroline: a new broad-spectrum cephalosporin. [2023]

8. New Zealand pubmed.ncbi.nlm.nih.gov

Use of Ceftaroline Fosamil in Children: Review of Current Knowledge and its Application. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Elexacaftor-Tezacaftor-Ivacaftor: The First Triple-Combination Cystic Fibrosis Transmembrane Conductance Regulator Modulating Therapy. [2020]

10. New Zealand pubmed.ncbi.nlm.nih.gov

Elexacaftor/Ivacaftor/Tezacaftor: First Approval. [2020]

11. Netherlands pubmed.ncbi.nlm.nih.gov

Use of cystic fibrosis inhaled medication before and after elexacaftor/tezacaftor/ivacaftor initiation. [2023]

12. United States pubmed.ncbi.nlm.nih.gov

Physiologically Based Pharmacokinetic Modeling of CFTR Modulation in People with Cystic Fibrosis Transitioning from Mono or Dual Regimens to Triple-Combination Elexacaftor/Tezacaftor/Ivacaftor. [2021]

13. United States pubmed.ncbi.nlm.nih.gov

Elexacaftor/Tezacaftor/Ivacaftor Treatment and Depression-related Events. [2023]