Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.
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.
cg: Reviewed Mod 12; updated EC to match clinicaltrials.gov
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Eligibility last updated 5/31/23. Questions regarding updates should be directed to the study team contact.