L-CsA + Standard of Care for Bronchiolitis Obliterans Syndrome

(BOSTON-3 Trial)

Not currently recruiting at 53 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Zambon SpA

Must be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Hypersensitivity to cyclosporine, New malignancy, others

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for Bronchiolitis Obliterans Syndrome (BOS), a serious lung condition that can occur after a lung transplant. The trial evaluates the safety and effectiveness of Liposomal Cyclosporine A (L-CsA, an immunosuppressant drug) when combined with the usual care for BOS patients. Participants will receive either a 5 mg or 10 mg dose of L-CsA, depending on whether they had a single or double lung transplant. This trial may suit those who have completed certain visits in a previous BOS study and follow a specific immune-suppressing medication plan. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that Liposomal Cyclosporine A (L-CsA) is being tested for its safety and effectiveness in treating lung conditions like bronchiolitis obliterans syndrome (BOS). In earlier studies, researchers added L-CsA to standard treatments to assess patient tolerance. The results showed that most patients tolerated it well, with some mild and manageable side effects reported.

In another study, researchers tested two different doses of L-CsA and found both doses safe for long-term use. While some side effects occurred, they weren't serious enough to halt treatment. These studies suggest that L-CsA could be a safe option for people with lung issues after a transplant. However, discussing potential risks with a healthcare provider remains important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Liposomal Cyclosporine A (L-CsA) because it offers a novel approach to treating Bronchiolitis Obliterans Syndrome (BOS) in lung transplant patients. Unlike standard treatments that focus on immunosuppressive drugs like tacrolimus or prednisone, L-CsA is delivered in a liposomal form, which may enhance drug delivery and minimize side effects. The 5 mg dose is designed for single lung transplant patients, while the 10 mg dose targets those with double lung transplants, optimizing treatment based on transplant type. This innovative delivery method could improve outcomes and reduce complications compared to current therapies.

What evidence suggests that this trial's treatments could be effective for bronchiolitis obliterans syndrome?

This trial will evaluate two different dosages of Liposomal Cyclosporine A (L-CsA) combined with standard care for patients with Bronchiolitis Obliterans Syndrome (BOS) following a lung transplant. Studies have shown that L-CsA is generally safe and can help maintain stable lung function in people with BOS. Research indicates that while L-CsA does not extend the time patients remain free from BOS, it effectively maintains lung health with minimal side effects. This treatment delivers cyclosporine directly to the lungs through inhalation, helping to prevent further lung damage. Initial findings suggest that this method may be a promising option for those dealing with BOS after a transplant. Participants in this trial will receive either L-CsA 5 mg or L-CsA 10 mg, each combined with standard care, to assess the effectiveness and safety of these dosages. ^{1 2 4 5 6}

Who Is on the Research Team?

Paola R Castellani, MD

Principal Investigator

Zambon SpA, Chief Medical Officer

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03656926

Efficacy + Safety of Liposome Cyclosporine A to Treat ... The objective of this trial was to assess the efficacy and safety of aerosolized liposomal cyclosporine A (L-CsA) as add-on therapy to standard of care ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S160061352208056X

A randomized controlled trial of liposomal cyclosporine ... Cyclosporine inhalation solution does not improve bronchiolitis obliterans syndrome-free survival following lung transplant: Results from the CYCLIST trial.

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/31687370/

A randomised single-centre trial of inhaled liposomal ... L-CsA was well tolerated and stabilised lung function in lung transplant recipients affected by BOS without systemic toxicity.

4. studyforbos.com studyforbos.com/study-overview

Study Overview | Boston Clinical Study The BOSTON research studies are being performed to evaluate the safety and efficacy of investigational L-CsA-i as a treatment for Bronchiolitis Obliterans ...

5. atsjournals.org atsjournals.org/doi/abs/10.1164/ajrccm-conference.2021.203.1_MeetingAbstracts.A1790

Study Design of Two Phase III, Prospective, Multicenter ... ... OUTCOME ... Trials Evaluating the Efficacy and Safety of Liposomal Cyclosporin A for Inhalation(L-CsA-i) in Patients with Bronchiolitis Obliterans Syndrome ...

6. clinicaltrials.gov clinicaltrials.gov/ct2/show/NCT04107675?term=BOSTON-4&draw=2&rank=1

NCT04107675 | A Safety Study of Liposomal Cyclosporine ... The primary objective of this study is to assess the tolerability and safety of two dose levels of aerosolized L-CsA vs placebo in addition to SoC therapy for ...