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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 Double Lung Transplant (BOSTON-2)

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ClinicalTrials.gov Identifier: NCT03656926
Recruitment Status : Recruiting
First Posted : September 3, 2018
Last Update Posted : June 5, 2019
Sponsor:
Information provided by (Responsible Party):
Breath Therapeutics Inc.

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 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.

Condition or disease Intervention/treatment Phase
Bronchiolitis Obliterans Drug: Liposomal Cyclosporine A Phase 3

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 110 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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 Double Lung Transplantation
Actual Study Start Date : March 29, 2019
Estimated Primary Completion Date : September 2021
Estimated Study Completion Date : October 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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



Primary Outcome Measures :
  1. Mean change in FEV1 (mL) from baseline to Week 48) [ Time Frame: Baseline to Week 48 ]

Secondary Outcome Measures :
  1. Mean change in FEV1/FVC from baseline to Week 48 [ Time Frame: Baseline to Week 48 ]
  2. Tiime 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 - 301 - SLT (BOSTON-1) which will be conducted in the same investigational centers in patients who have undergone single-lung transplantations.


Other Outcome Measures:
  1. Adverse Events [ Time Frame: Baseline through study completion (52 weeks) ]
  2. 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

  3. 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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. 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.
  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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03656926


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

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Locations
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United States, Arizona
St. Joseph's Hospital Recruiting
Phoenix, Arizona, United States, 85302
Contact: Rajat Walia, MD       rajat.walia@dignityhealth.org   
United States, California
UCLA Medical Center Not yet recruiting
Los Angeles, California, United States, 90095
Contact: Samuel Weigt, MD       sweigt@mednet.ucla.edu   
Stanford University Hospital Not yet recruiting
Palo Alto, California, United States, 94305
Contact: Gundeep Dhillon, MD       gdhillon@stanford.edu   
UC San Francisco Not yet recruiting
San Francisco, California, United States, 94143
Contact: Steven Hays, MD       steven.hays@ucsf.edu   
United States, Florida
Mayo Clinic Jacksonville Not yet recruiting
Jacksonville, Florida, United States, 32224
Contact: Si Pham, MD       pham.si@mayo.edu   
United States, Indiana
Indiana University Recruiting
Indianapolis, Indiana, United States, 46202
Contact: Chadi Hage, MD       chage@iu.edu   
United States, Kentucky
University of Kentucky Albert B. Chandler Hospital Not yet recruiting
Lexington, Kentucky, United States, 40508
Contact: Maher Baz, MD       maher.baz@uky.edu   
United States, Maryland
University of Maryland Not yet recruiting
Baltimore, Maryland, United States, 21201
Contact: Bartley Griffith, MD       bgriffith@gmail.com   
Johns Hopkins University Hospital Not yet recruiting
Baltimore, Maryland, United States, 21287
Contact: Pali Shah, MD       pdedhiy2@jymi.edu   
United States, Missouri
Barnes Jewish Hospital Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Ramsey Hachem, MD       rhachem@wustl.edu   
United States, New York
Columbia University Medical Center Not yet recruiting
New York, New York, United States, 10032
Contact: Selim Arcasoy, MD       sa2059@cumc.columbia.edu   
United States, North Carolina
Duke University Medical Center Not yet recruiting
Durham, North Carolina, United States, 27110
Contact: John Reynolds, MD       john.reynolds@duke.edu   
United States, Ohio
Cleveland Clinic Not yet recruiting
Cleveland, Ohio, United States, 44195
Contact: Maria Budev, DO       budevm@ccf.org   
United States, Pennsylvania
University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Maria Crespo, MD       maria.crespo@uphs.upenn.edu   
Temple University Hospital Not yet recruiting
Philadelphia, Pennsylvania, United States, 19140
Contact: Gerard Criner, MD       gerard.criner@tuhs.temple.edu   
University of Pittsburgh Medical Center Recruiting
Pittsburgh, Pennsylvania, United States, 15232
Contact: Joseph Pilewski, MD       pilewskijm@upmc.edu   
United States, Texas
Baylor University Medical Center Recruiting
Dallas, Texas, United States, 75246
Contact: Puneet Garcha, MD       puneet.garcha@bswhealth.org   
Houston Methodist Hospital Recruiting
Houston, Texas, United States, 77030
Contact: Howard Huang, MD       hjhuang@houstonmethodist.og   
United States, Virginia
Inova Hospital Not yet recruiting
Falls Church, Virginia, United States, 22042
Contact: Shambhu Aryal, MD       shambhu.aryal@inova.org   
Austria
Waehringer Guertel Not yet recruiting
Vienna, Austria
Contact: Peter Jaksch, MD       peter.jaksch@meduniwien.ac.at   
Belgium
CHU Erasme Recruiting
Brussels, Belgium
Contact: Christiane Knoop, MD       christiane.knoop@erasme.ulb.ac.be   
France
CHU Hopital Nord Recruiting
Marseille, France
Contact: Martine Reynaud-Gaubert, MD       martinelouise.reynaud@ap-hm.fr   
Marie-Lannelongue Recruiting
Paris, France
Contact: Gerome Le Pavec, MD       lepavec@gmail.com   
Hôpitaux Universitaires de Strasbourg Recruiting
Strasbourg, France
Contact: Romain Kessler, MD       romain.kessler@chru-strasbourg.fr   
Germany
Hannover Medical School Recruiting
Hannover, Germany
Contact: Jens Gottlieb, MD       gottlieb.jens@mh-hannover.de   
LMU Klinikum Großhadern Not yet recruiting
Munich, Germany
Contact: Jurgen Behr, MD       juergen.behr@med.uni-muenchen.de   
Israel
Rabin Medical Center Recruiting
Petah tikva, Israel
Contact: Mordechai Kramer, MD       kramerm@clalit.org.il   
Spain
Hospital Universitari Vall d'Hebron Recruiting
Barcelona, Spain
Contact: Victor Monforte, MD       vmonforte@vhebron.net   
Complexo Hospitalario de A Coruna Not yet recruiting
Coruña, Spain
Contact: Mercedes De la Torre, MD       mercedes.de.la.torre.bravos@sergas.es   
Reina Sofia University Hospital Recruiting
Córdoba, Spain
Contact: Javier Redel-Montero, MD       javierredel@msn.com   
H. U. 12 de Octubre Not yet recruiting
Madrid, Spain
Contact: Alicia de Pablo Gafas, MD       alic1575@separ.es   
Hospital Puerta de Hierro Not yet recruiting
Madrid, Spain
Contact: Piedad Ussetti, MD       pussetti.hpth@salud.madrid.org   
Hospital Marques de Valdecilla Recruiting
Santander, Spain
Contact: Jose Cifrian, MD       josemanuel.cifrian@scsalud.es   
University Hospital LA F3 Recruiting
Valencia, Spain
Contact: Amparo Sole, MD       sole_amparo@gva.es   
United Kingdom
Royal Papworth Hospital Not yet recruiting
Cambridge, United Kingdom
Contact: Jasvir Parmar, MD       jas.parmar@nhs.net   
University of Manchester Not yet recruiting
Manchester, United Kingdom
Contact: Mohamed Al-Aloul, MD       mohamed.alaloul@mft.nhs.uk   
Sponsors and Collaborators
Breath Therapeutics Inc.
Investigators
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Study Director: Noreen R Henig, MD Breath Therapeutics, Chief Medical Officer

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Responsible Party: Breath Therapeutics Inc.
ClinicalTrials.gov Identifier: NCT03656926     History of Changes
Other Study ID Numbers: BT - L-CsA - 302 - DLT
First Posted: September 3, 2018    Key Record Dates
Last Update Posted: June 5, 2019
Last Verified: June 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Bronchiolitis
Bronchiolitis Obliterans
Bronchitis
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Tract Infections
Cyclosporins
Cyclosporine
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antifungal Agents
Anti-Infective Agents
Dermatologic Agents
Antirheumatic Agents
Calcineurin Inhibitors