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Purpose

This is a Phase III randomized, controlled clinical trial of L-CsA for the treatment of bronchiolitis obliterans syndrome in adults diagnosed with BOS following double lung transplant. Patients will receive either L-CsA (10 mg) via the PARI Investigational eFlow® Device twice daily plus Standard of Care (SoC) treatment, or SoC alone, for a period of 48 weeks. All patients will be eligible to continue in an open-label extension trial of L-CsA following completion of BOSTON-2.

Conditions

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  1. Adult patients ≥ 18 years who received a double lung transplant at least 12 months prior to Screening.
  2. Patients with clinically defined BOS (CLAD - BOS phenotype) with screening FEV1 between 85-60% of personal best FEV1 value post-transplant.
  3. Patients with an FEV1/FVC ratio of </= 0.7.
  4. Patients in whom the diagnosis of BOS has been confirmed by the elimination of other possible causes of obstructive lung disease.
  5. Patients with a diagnosis of BOS made at least 1 year after transplant surgery and within 12 months prior to the Screening Visit.
  6. Patients should be on a three-drug 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. The regimen must be stable for at least 4 weeks prior to randomization with respect to the therapeutic agents.
  7. Patients must consent to retrieve prespecified data from the historic medical record (e.g., information related to the transplant surgery; spirometry data; medication use).
  8. Patients must be receiving or have received post-transplant prophylaxis against Cytomegalovirus (CMV) and Pneumocystis pneumonia as per SoC at the site.
  9. 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.
  10. 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 of the protocol through their End of Study Visit.
  11. 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 (RAS), etc.
  2. Cystic Fibrosis patients with multi-drug resistant infections not responding to available anti-microbial therapies.
  3. Patients with acute antibody-mediated rejection at Screening. In this context, clinically stable patients displaying low and stable levels of donor-specific antibodies (DSA) at the Screening Visit (as judged by the Investigator) are eligible for the study.
  4. Active acute bacterial, viral, or fungal infection not successfully resolved at least 4 weeks prior to the Screening Visit.
  5. Mechanical ventilation within 12 weeks prior to Randomization.
  6. Patients with uncontrolled hypertension.
  7. Patient has baseline resting oxygen saturation of < 89% on room air or use of supplemental oxygen.
  8. 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 ag Screening and/or Randomization Visit.
  9. Known hypersensitivity to L-CsA or to cyclosporine A.
  10. Patients with chronic renal failure, defined as serum creatinine > 2.5 mg/ dL, or requiring chronic dialysis.
  11. Patients with liver disease and serum bilirubin > 3-fold upper limit of normal range or transaminases > 2.5 upper limit of normal range.
  12. 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.
  13. Pregnant women or women who are unwilling to use appropriate birth control to avoid pregnancy through their End of Study Visit.
  14. Women who are currently breastfeeding.
  15. 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.
  16. Patients who have received extracorporeal photophoresis (ECP) for treatment of BOS within 1 month prior to Randomization.
  17. Patients who are currently participating in an interventional clinical trial.
  18. Psychiatric disorders or altered mental status precluding understanding of the informed consent process and/or completion of the necessary procedures.
  19. 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.

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
Single (Outcomes Assessor)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
L-CsA treatment plus SoC
L-CsA 10 mg twice daily for 48 weeks, plus Standard of Care Therapy
  • Drug: Liposomal Cyclosporine A
    delivered via the PARI eFlow® Device
No Intervention
Standard of Care alone
Standard of Care Therapy

Recruiting Locations

UK Center for Clinical and Translational Science and nearby locations

University of Kentucky Albert B. Chandler Hospital
Lexington, Kentucky 40508
Contact:
Maher Baz, MD
maher.baz@uky.edu

More Details

NCT ID
NCT03656926
Status
Recruiting
Sponsor
Breath Therapeutics Inc.

Study Contact

Tammy Abuan, RN, MS
+1.650.272.0655
t.abuan@breath-therapeutics.com

Detailed Description

Regardless of treatment allocation, all patients will continue to receive their SoC regimen for maintenance of the lung allograft. Eligible patients for the clinical trial must have a tacrolimus-based triple-drug therapy in combination with mycophenolate mofetil or its equivalent and a corticosteroid.

A total of 11 visits will be performed during the clinical trial. After informed consent has been obtained, a Screening Visit will be carried out in order to check general eligibility for participation. At the Randomization Visit, inclusion and exclusion criteria will be re-checked and spirometry performed. During the 48-week treatment period, visits are scheduled every 4-8 weeks. If a patient has an event that meets one of the criteria for progression of BOS, he/she will return to the clinic within 2-weeks for an unscheduled visit to have spirometry and other procedures performed.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.