L-CsA + Standard of Care for Bronchiolitis Obliterans Syndrome

(BOSTON-3 Trial)

Recruiting at 49 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Zambon SpA

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: Unknown

Duration: 144 weeks

262 Participants Needed

Trial Summary

What is the purpose of this trial?

The objective of the trial is to assess the long-term safety and efficacy of L-CsA plus Standard of Care (SoC) in the treatment of BOS in single (SLT) and double lung transplant (DLT) recipients.

Will I have to stop taking my current medications?

The trial requires participants to continue their current three-drug maintenance regimen of immunosuppressive agents, including tacrolimus or another CNI, a second agent like MMF or azathioprine, and a systemic corticosteroid such as prednisone.

What data supports the effectiveness of the drug Liposomal Cyclosporine A for treating bronchiolitis obliterans syndrome?

Research shows that inhaled liposomal cyclosporine A may help prevent the progression of bronchiolitis obliterans syndrome in lung transplant patients, and aerosol cyclosporine has been associated with increased survival compared to conventional therapy alone. ^{1 2 3 4 5}

Is liposomal cyclosporine A safe for humans?

Liposomal cyclosporine A has been generally well tolerated in studies, with some mild side effects like tracheal irritation and coughing, which resolved quickly. In a study with volunteers, no significant changes in blood tests were observed, indicating it is generally safe for human use. ^{1 3 5 6 7}

How is the drug Liposomal Cyclosporine A unique for treating bronchiolitis obliterans syndrome?

Liposomal Cyclosporine A is unique because it is administered as an inhaled treatment, allowing for direct delivery to the lungs, which may enhance its effectiveness in preventing bronchiolitis obliterans syndrome after lung transplantation. This approach differs from traditional systemic immunosuppressive therapies and offers a novel way to potentially improve lung transplant outcomes. ^{1 3 4 7 8}

Research Team

Paola R Castellani, MD

Principal Investigator

Zambon SpA, Chief Medical Officer

Eligibility Criteria

This trial is for post lung transplant patients with Bronchiolitis Obliterans Syndrome (BOS) who are on a three-drug immunosuppressive regimen. They must have completed prior BOSTON trials without early termination or consent withdrawal, not be pregnant or breastfeeding, agree to use contraception, and have no new cancers except certain skin carcinomas.

Inclusion Criteria

I am on a 3-drug regimen including tacrolimus (or similar), MMF/azathioprine, and a steroid.

Women of childbearing potential must have a negative serum pregnancy test within 7 days prior to Visit 1 and must agree to use one of the methods of contraception listed in Appendix II through their End of Study Visit.

I understand the trial's risks, have given consent, can follow the schedule, and can inhale aerosols.

Exclusion Criteria

Pregnant women or women who are unwilling to use appropriate birth control to avoid pregnancy through their End of Study Visit.

Women who are currently breastfeeding.

I have not taken any experimental drugs, except L-CsA, in the last 4 weeks.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive L-CsA plus Standard of Care for up to 144 weeks, with BID inhalation using the L-CsA eFlow device

144 weeks

Regular visits for inhalation monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension

Participants continue receiving L-CsA plus Standard of Care beyond the initial trial period

Long-term

Treatment Details

Interventions

• Liposomal Cyclosporine A 10 mg
• Liposomal Cyclosporine A 5 mg

Trial Overview The study aims to evaluate the long-term safety and effectiveness of Liposomal Cyclosporine A (L-CsA) at two different doses added to Standard of Care in treating BOS after single or double lung transplants.

Participant Groups

Group I: L-CsA 5 mg plus Standard of Care Experimental Treatment 1 Intervention

L-CsA 5 mg twice daily plus Standard of Care for up to 144 weeks for patients post Single Lung Transplant

Group II: L-CsA 10 mg plus Standard of Care Experimental Treatment 1 Intervention

L-CsA 10 mg twice daily plus Standard of Care for up to 144 weeks for patients post Double Lung Transplant

Who Is Running the Clinical Trial?

Zambon SpA

Lead Sponsor

Trials

31

Recruited

6,300+

References

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

A randomized controlled trial of liposomal cyclosporine A for inhalation in the prevention of bronchiolitis obliterans syndrome following lung transplantation. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Aerosol cyclosporin therapy in lung transplant recipients with bronchiolitis obliterans. [2019]

3. England pubmed.ncbi.nlm.nih.gov

A randomised single-centre trial of inhaled liposomal cyclosporine for bronchiolitis obliterans syndrome post-lung transplantation. [2022]

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

Conversion from cyclosporine to tacrolimus stabilizes the course of lung function in lung transplant recipients with bronchiolitis obliterans syndrome. [2013]

5. England pubmed.ncbi.nlm.nih.gov

Selective transfer of cyclosporin to thoracic lymphatic systems by the application of lipid microspheres. [2009]

6. England pubmed.ncbi.nlm.nih.gov

Low-dose cyclosporin therapy of ocular inflammation: preliminary report of a long-term follow-up study. [2019]

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

Tolerance of volunteers to cyclosporine A-dilauroylphosphatidylcholine liposome aerosol. [2013]

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

Lung deposition of a liposomal cyclosporine A inhalation solution in patients after lung transplantation. [2016]