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A Clinical Trial to Demonstrate the Effectiveness and Safety of Liposomal Cyclosporine A Inhalation Solution in the Treatment of Bronchiolitis Obliterans Syndrome in Patients Post Single Lung Transplant (BOSTON-1)

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ClinicalTrials.gov Identifier: NCT03657342
Recruitment Status : Recruiting
First Posted : September 5, 2018
Last Update Posted : June 5, 2019
Sponsor:
Information provided by (Responsible Party):
Breath Therapeutics Inc.

Tracking Information
First Submitted Date  ICMJE August 30, 2018
First Posted Date  ICMJE September 5, 2018
Last Update Posted Date June 5, 2019
Actual Study Start Date  ICMJE March 26, 2019
Estimated Primary Completion Date December 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 13, 2018)
Mean change in FEV1 (mL) from baseline to Week 48 [ Time Frame: Baseline to Week 48 ]
Original Primary Outcome Measures  ICMJE Not Provided
Change History Complete list of historical versions of study NCT03657342 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: June 3, 2019)
  • Mean change in FEV1/FVC from baseline to Week 48 [ Time Frame: Baseline to Week 48 ]
  • 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. ]
    defined as the earliest of the following:
    • Absolute decrease from baseline in FEV1 >/= 10% or >/= 200 mL and absolute decrease in FEV1/FVC of > 5% OR
    • Change in BOS Severity, OR
    • Re-transplantation, OR
    • Death from respiratory failure This endpoint will be assessed in a combined analysis with a similar Phase III clinical trial, BT - L-CsA - 302 - DLT (BOSTON-2) which will be conducted in the same investigational centers in patients who have undergone double-lung transplantations.
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures
 (submitted: September 13, 2018)
  • Adverse Events [ Time Frame: Baseline through study completion (52 weeks) ]
  • Acute tolerability of L-CsA [ Time Frame: Baseline through Week 48 ]
    change in forced expiratory volume in one second (FEV1); reports of cough or shortness of breath
  • Hematology and Serum Chemistry Parameters [ Time Frame: From date of randomization until end of study participation (52 weeks) ]
    Number of patients with treatment-related changes in hematology or serum chemistry parameters assessed by CTCAE v5.0.
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Clinical Trial to Demonstrate the Effectiveness and Safety of Liposomal Cyclosporine A Inhalation Solution in the Treatment of Bronchiolitis Obliterans Syndrome in Patients Post Single Lung Transplant
Official Title  ICMJE A Phase III, Prospective, Multicenter, Randomized, Controlled Clinical Trial to Demonstrate the Effectiveness and Safety of Liposomal Cyclosporine A (L-CsA) Inhalation Solution Delivered Via the PARI Investigational eFlow® Device Plus Standard of Care Versus Standard of Care Alone in the Treatment of Bronchiolitis Obliterans Syndrome in Patients Post Single Lung Transplantation
Brief Summary 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 single lung transplant. Patients will receive either L-CsA (5 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-1.
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Bronchiolitis Obliterans
Intervention  ICMJE Drug: Liposomal Cyclosporine A
delivered via the PARI eFlow® Device
Study Arms  ICMJE
  • Experimental: L-CsA treatment plus SoC
    L-CsA 5 mg twice daily for 48 weeks Standard of Care Therapy
    Intervention: Drug: Liposomal Cyclosporine A
  • No Intervention: Standard of Care alone
    Standard of Care Therapy
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: September 13, 2018)
110
Original Enrollment  ICMJE Not Provided
Estimated Study Completion Date  ICMJE January 2022
Estimated Primary Completion Date December 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Adult patients ≥ 18 years who received a single 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. Patients with Cystic Fibrosis.
  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. Patients with chronic infection or colonization who are clinically stable as per judgement of the Investigator are eligible for the study.
  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 at 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Tammy Abuan, RN, MS +1.650.272.0655 t.abuan@breath-therapeutics.com
Listed Location Countries  ICMJE France,   Germany,   Israel,   Spain,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03657342
Other Study ID Numbers  ICMJE BT - L-CsA - 301 - SLT
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Breath Therapeutics Inc.
Study Sponsor  ICMJE Breath Therapeutics Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Noreen R Henig, MD Breath Therapeutics, Chief Medical Officer
PRS Account Breath Therapeutics Inc.
Verification Date June 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP