Clinical research study to investigate efficacy and safety of Liposomal Cyclosporine A (L-CsA) in patients with Bronchiolitis Obliterans Syndrome after Single or Double Lung Transplantation.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Zambon S.p.A.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

Trial duration

1 Apr 2020 → 26 Feb 2026

Decision date (initial)

2024-07-30

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Zambon SpA

External identifiers

EU CT number

2024-512448-41-00

EudraCT number

2019-002987-29

ClinicalTrials.gov

NCT04039347

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Therapy, Efficacy

To assess the long-term safety and efficacy of L-CsA plus SoC in the treatment of BOS in single and double lung transplant recipients, who have completed either BOSTON-1 or BOSTON-2 study, and have taken the decision of continuing BOSTON- 3, based on their individual benefit risk considerations as discussed with their study doctor.

Conditions and MedDRA coding

Bronchiolitis Obliterans Syndrome in Patients post Single or post Double Lung Transplantation

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Patients who have completed all visits through the End of Treatment Visit in either BOSTON-1 or BOSTON-2, did not withdraw informed consent, and did not prematurely terminate study drug administration
2. Patients should be on a maintenance regimen of immunosuppressive agents as defined in the Boston 1 and Boston 2 studies, (i.e. tacrolimus, a second agent such as but not limited to mycophenolate mofetil (MMF) or azathioprine, and a systemic corticosteroid such as prednisone as third agent. Concomitant azithromycin for prophylaxis or treatment of BOS is also allowed), or according to Investigator judgment.
3. Patients capable of understanding the purposes and risks of the clinical trial, who have given written informed consent and agree to comply with the clinical trial requirements/visit schedules, and who are capable of aerosol inhalation.
4. Women of childbearing potential must have a negative serum or urine pregnancy test within 7 days prior to Visit 1 and must agree to use one of the methods of contraception listed in Appendix II of the protocol through their End of Study Visit.

Exclusion criteria 9

1. Known hypersensitivity to L-CsA or to cyclosporine A.
2. Patients who experienced an AE related to study drug that led to permanent study drug discontinuation in BOSTON-1 or BOSTON-2.
3. Patients who developed a new malignancy while participating in BOSTON-1 or BOSTON-2, including post-transplant lymphoproliferative disorder, with the exception of treated, localized basal and squamous cell carcinomas.
4. Pregnant women or women who are unwilling to use appropriate birth control to avoid pregnancy through their End of Study Visit.
5. Women who are currently breastfeeding.
6. Receipt of an investigational drug, other than L-CsA, as part of a clinical trial within 4 weeks prior to Visit 1. This is defined as any treatment that is implemented under an Investigational New Drug (IND) or compassionate use.
7. Patients who are currently participating in an interventional clinical trial, other than BOSTON-1 or BOSTON-2.
8. Psychiatric disorders or altered mental status precluding understanding of the informed consent process and/or completion of the necessary procedures
9. Any co-existing medical condition that in the Investigator's judgment will substantially increase the risk associated with the patient's participation in the clinical trial.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 18

1. SAFETY: Adverse events (AEs)
2. SAFETY: Acute tolerability of IMP after initial dosing (only in patients randomized to SoC in BOSTON-1 or BOSTON-2 study)
3. SAFETY: Clinical laboratory parameters
4. SAFETY: Vital signs
5. SAFETY: Physical examinations
6. SAFETY: Renal function
7. EFFICACY: Mean change in forced expiratory volume in 1 second (FEV1) (mL) from baseline to approximately each year until End of Study
8. EFFICACY: Mean change in FEV1/forced vital capacity (FVC) from baseline to approximately each year until End of Study
9. EFFICACY: Time to progression of BOS, defined as the earliest of the following: o Absolute decrease from baseline in FEV1 ≥ 10% or ≥ 200 mL and absolute decrease in FEV1/FVC of > 5%, OR o Worsening of BOS grade (according to criteria in Verleden 2019), OR o Re-transplantation, OR o Death from respiratory failure
10. EFFICACY: Rate of decline of FEV1 from baseline to last treatment day
11. EFFICACY: Use of additional immunosuppressive therapy
12. EFFICACY: Proportion of patients experiencing re-transplantation due to BOS
13. EFFICACY: Proportion of patients with fatal outcome due to respiratory failure
14. EFFICACY: Change in BOS severity (according to criteria in Verleden 2019)
15. EFFICACY: Mean relative intra-individual change of FEV1 between start of treatment (baseline) and end of study participation
16. EFFICACY: Euro Quality of Life Questionnaire (EQ-5D-5L)
17. EFFICACY: Hospitalization days
18. EFFICACY: Absolute and relative change from baseline in: o Forced mid-expiratory flow (FEF25-75) o Forced Vital Capacity (FVC)

Investigational products

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

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Zambon S.p.A.

Sponsor organisation

Zambon S.p.A.

Address

Via Lillo Del Duca 10

City

Bresso

Postcode

20091

Country

Italy

Scientific contact point

Organisation

Zambon S.p.A.

Contact name

Ferdinando Ceravolo

Public contact point

Organisation

Zambon S.p.A.

Contact name

Paola Castellani

Third parties 5

Locations

6 EU/EEA countries · 12 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 38 files

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

Application history

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