Efficacy + Safety of Liposome Cyclosporine A to Treat Bronchiolitis Obliterans Post Single Lung Transplant (BOSTON-1)

• Register: ClinicalTrials.gov
• Last refreshed on: 16 October 2023
• Main ID: NCT03657342
• Date of registration: 30/08/2018
• Prospective Registration: Yes
• Primary sponsor: Zambon SpA
• Public title: Efficacy + Safety of Liposome Cyclosporine A to Treat Bronchiolitis Obliterans Post Single Lung Transplant (BOSTON-1) BOSTON-1
• Scientific title: A Phase III Clinical Trial to Demonstrate Efficacy / Safety of Liposomal Cyclosporine A + Standard of Care (SoC) vs SoC Alone in Treating Chronic Lung Allograft Dysfunction / Bronchiolitis Obliterans in Patients Post Single Lung Transplant
• Date of first enrolment: April 2, 2019
• Target sample size: 220
• Recruitment status: Active, not recruiting
• URL: https://clinicaltrials.gov/ct2/show/NCT03657342
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Single (Outcomes Assessor).
• Phase: Phase 3

Countries of recruitment

Belgium, France, Germany, Israel, Spain, United Kingdom, United States

Contacts

• Name: Paola Castellani, MD
• Affiliation: Zambon SpA, Chief Medical Officer

Key inclusion & exclusion criteria

Inclusion Criteria:

1. Adult patients = 18 years who received a single lung transplant at least 12 months
prior to Screening.

2. Patients with BOS diagnosis defined as CLAD-BOS phenotype with:

1. Screening FEV1 between 85-51% of personal best FEV1 value post-transplant OR

2. Screening FEV1 >85% of personal best FEV1 associated with EITHER a = 200 mL
decrease in FEV1 in the previous 12 months OR according to medical history
showing BOS progression.

3. Diagnosis of CLAD-BOS must be made at least 12 months after lung transplantation and

1. within 12 months prior to the screening visit OR

2. more than 12 months from screening and patient must have shown a decline in FEV1
= 200ml in the previous 12 months before screening, which is not due to acute
infection or acute organ rejection.

4. Patients in whom the diagnosis of BOS has been confirmed by the elimination of other
possible causes of obstructive or restrictive lung disease (CLAD - RAS phenotype, see
Protocol Specific Definitions).

5. Patients should be on a maintenance regimen of immunosuppressive agents including
tacrolimus, a second agent such as but not limited to MMF or azathioprine, and a
systemic corticosteroid such as prednisone as third agent. The regimen must be stable
within 4 weeks prior to randomization with respect to the therapeutic agents.

6. 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. Patients must
consent to retrieve prespecified data from the historic medical record (e.g.,
information related to the transplant surgery; spirometry data; medication use).

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

8. Patients have no concomitant diagnoses that are considered fatal within one year (12
months) of Screening.

Exclusion Criteria:

1. Patients with confirmed other causes for loss of lung function, such as acute
infection, acute rejection, restrictive allograft syndrome (CLAD - RAS phenotype, see
Protocol Specific Definition ), etc.

2. Patients with acute antibody-mediated rejection at Screening. In this context,
clinically stable patients (as judged by the Investigator) with detectable levels of
donor specific antibodies (DSA) at the Screening Visit are eligible for the study.

3. Active acute bacterial, viral, or fungal infection not successfully resolved at least
4 weeks prior to the Screening Visit. Patients with chronic infection or colonization
who are clinically stable as per judgement of the Investigator are eligible for the
study.

4. Mechanical ventilation within 12 weeks prior to Randomization.

5. Patients with uncontrolled hypertension.

6. Patient has baseline resting oxygen saturation of < 89% on room air or use of
supplemental oxygen at rest.

7. Evidence of functional airway stenosis (e.g., bronchomalacia/tracheomalacia, airway
stents, or airways requiring balloon dilatations to maintain patency) with onset after
the initial diagnosis of BOS and ongoing at Screening and/or Baseline Visit.

8. Known hypersensitivity to L-CsA or to cyclosporine A.

9. Patients with chronic renal failure, defined as serum creatinine > 2.5 mg/dL at
screening, or requiring chronic dialysis.

10. Patients with liver disease and serum bilirubin > 3-fold upper limit of normal range
or transaminases > 2.5 upper limit of normal range.

11. Patients with active malignancy within the previous 2 years, including post-transplant
lymphoproliferative disorder, with the exception of treated, localized basal and
squamous cell carcinomas.

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

13. Women who are currently breastfeeding.

14. Receipt of an investigational drug as part of a clinical trial within 4 weeks prior to
the Screening Visit. This is defined as any treatment that is implemented under an
Investigational New Drug (IND) or compassionate use.

15. Patients who have received extracorporeal photophoresis (ECP) for treatment of BOS
within 1 month prior to Randomization.

16. Patients who are currently participating in an interventional clinical trial.

17. Psychiatric disorders or altered mental status precluding understanding of the
informed consent process and/or completion of the necessary procedures.

18. 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.



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Chronic Rejection of Lung Transplant

Lung Transplant Failure and Rejection

Lung Transplant Rejection

Bronchiolitis Obliterans

Chronic Lung Allograft Dysfunction

Lung Transplant; Complications

Intervention(s)

Drug: Liposomal Cyclosporine A

Drug: standard of care

Primary Outcome(s)

Mean change in FEV1 (mL) from baseline to Week 48 [Time Frame: Baseline to Week 48]

Secondary Outcome(s)

Time to Progression of BOS [Time Frame: From date of randomization until the date of first documented progression of BOS, or date of retransplantation, or date of death from respiratory failure, whichever came first, assessed up to 52 weeks.]

Mean change in FEV1/FVC from baseline to Week 48 [Time Frame: Baseline to Week 48]

Secondary ID(s)

2018-003204-39

BT - L-CsA - 301 - SLT

Source(s) of Monetary Support

Please refer to primary and secondary sponsors