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A Safety Study of Liposomal Cyclosporine A to Treat Bronchiolitis Obliterans Syndrome Following Allogeneic Hematopoietic Stem Cell Transplant (BOSTON-4)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04107675
Recruitment Status : Recruiting
First Posted : September 27, 2019
Last Update Posted : March 18, 2020
Sponsor:
Information provided by (Responsible Party):
Breath Therapeutics Inc.

Brief Summary:
This is a Phase II prospective, multi-center, single-blind, randomized clinical trial of safety in the treatment of BOS 1 in adult recipients of an allogeneic hematopoetic stem cell transplant. Twenty-four patients are planned for enrollment. The clinical trial will be conducted in approximately 20 centers in Germany, France, and Spain. Patients will be randomly allocated 1:1:1 to receive either L-CsA (10 mg bid or 5 mg bid) plus Standard of Care, or liposomal placebo plus Standard of Care. Investigational Medicinal Product will be administered for up to 12 weeks.

Condition or disease Intervention/treatment Phase
Bronchiolitis Obliterans GVHD, Chronic Stem Cell Transplant Complications Drug: Liposomal Cyclosporine A Drug: Liposomal Placebo Phase 2

Detailed Description:
Development of BOS after hematopoetic stem cell transplant (HSCT) is a major cause of morbidity and mortality; treatment options are limited and have not been optimized by well-conducted clinical trials. The hypothesis that local delivery of CsA by aerosol inhalation will achieve higher intrapulmonary concentration than by systemic administration alone, with limited toxicity compared to similar systemic doses due to minimal absorption of drug into the blood circulation has been substantiated by previous studies. The objectives of this study are to assess the tolerability, safety, PK, and exploratory efficacy of two dose levels of aerosolized L-CsA vs placebo in addition to SoC therapy for the treatment of BOS in adult allogeneic HSCT recipients.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 24 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Treatment
Official Title: A Phase IIa Multi-Center, Randomized, Single-Blind Safety Study of Liposomal Cyclosporine A to Treat Bronchiolitis Obliterans Syndrome Following Allogeneic Hematopoietic Stem Cell Transplantation
Actual Study Start Date : February 11, 2020
Estimated Primary Completion Date : December 2020
Estimated Study Completion Date : January 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: L-CsA 10 mg plus Standard of Care
Liposomal Cyclosporine A 10 mg bid for 12 weeks
Drug: Liposomal Cyclosporine A
Liposomal Cyclosporine A is administered with the PARI L-CsA eFlow Nebulizer.

Experimental: L-CsA 5 mg plus Standard of Care
Liposomal Cyclosporine A 5 mg bid for 12 weeks
Drug: Liposomal Cyclosporine A
Liposomal Cyclosporine A is administered with the PARI L-CsA eFlow Nebulizer.

Placebo Comparator: Liposomal Placebo plus Standard of Care
Liposomal Placebo 2.5 mL bid for 12 weeks
Drug: Liposomal Placebo
Liposomal Placebo is administered with the PARI L-CsA eFlow Nebulizer.




Primary Outcome Measures :
  1. Investigational Medicinal Product Tolerability [ Time Frame: Baseline to Week 4 ]
    Change in FEV1


Secondary Outcome Measures :
  1. Adverse Events [ Time Frame: through study completion, up to 3 years ]
    Number of participants with treatment-related adverse events as assessed by CTCAE v4.0.

  2. Hematology and Serum Chemistry Parameters [ Time Frame: through study completion, up to 3 years ]
    Number of participants with treatment-related adverse events as assessed by CTCAE v4.0.

  3. Vital Signs [ Time Frame: through study completion, up to 3 years ]
    Number of participants with treatment-related adverse events as assessed by CTCAE v4.0.

  4. Investigational Medicinal Product Tolerability [ Time Frame: Baseline to Week 12 ]
    Change in FEV1


Other Outcome Measures:
  1. Peak Plasma Concentration (Cmax) [ Time Frame: Day 1 (after receiving the first dose of study drug) ]
  2. Pharmacokinetic Parameters - CsA Levels [ Time Frame: Weeks 1, 4, 8, and 16 ]
    Whole Blood Trough Levels

  3. FEV1 Percent Predicted [ Time Frame: Baseline through Week 16 ]
    Change in FEV1 percent predicted

  4. FEV1/FVC [ Time Frame: Baseline through Week 16 ]
    Change in FEV1/FVC

  5. Quality of Life Questionnaire [ Time Frame: Baseline through Week 8 ]
    The EuroQoL Health-related Quality of Life tool, Youth Version, is a dimple, generic measure of health.

  6. Time to Peak Plasma Concentration (Tmax) [ Time Frame: Day 1 (after receiving the first dose of study drug) ]
  7. Area Under the Plasma Concentration versus Time Curve (AUC) [ Time Frame: Day 1 (after receiving the first dose of study drug) ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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. Age >/= 18 years
  2. Patient must have a history of allogeneic HSCT, regardless of source of stem cell or donor or indication for allogeneic HSCT
  3. Documented diagnosis of chronic Graft versus Host Disease (cGvHD) in any organ other than the lung. If BOS is the only manifestation of cGvHD, lung biopsy must have been performed before entering the trial to confirm BOS diagnosis.
  4. Confirmed diagnosis of BOS Score 1 [Jagasia et al. 2015] within > 6 months and < 3 years after allo-HSCT:

    FEV1/FVC < 0.7 at Screening Visit AND Post-bronchodilator FEV1 >/= 60 and ≤ 79% predicted at Screening Visit AND

    • 10% decline of FEV1 % predicted within 24 months prior to Screening Visit AND Absence of acute infection in the respiratory tract.
  5. Patient must be capable of understanding the purposes and risks of the study, has given written informed consent, and agrees to comply with the study requirements.
  6. Patient is capable of aerosol inhalation.
  7. Women of childbearing potential must have a negative serum or urine pregnancy test at screening and at randomization visit.

Exclusion Criteria:

  1. Active bacterial, viral (as confirmed by multiplex PCR) or fungal infection not successfully resolved at least 4 weeks prior to the Screening Visit.
  2. Chronic renal dysfunction with serum creatinine >/= 2.5 mg/dL or need for renal dialysis.
  3. Chronic hepatic dysfunction with serum total bilirubin > 5x upper limit of normal (ULN), transaminases > 5x ULN, or alkaline phosphatase > 5x ULN.
  4. Evidence of relapse of the primary malignancy which warranted allogeneic bone marrow transplant.
  5. Use of azithromycin within 4 weeks prior to Randomization (Visit 1).
  6. Use of zafirlukast during the study period.
  7. Chronic oxygen use or use of non-invasive ventilation.
  8. Active smokers (i.e. any kind of inhaled nicotine consumption).
  9. Pregnant women or women who are unwilling to use appropriate birth control to avoid pregnancy over the course of the clinical trial.
  10. Women who are currently breastfeeding.
  11. Known hypersensitivity to L-CsA or to cyclosporine A.
  12. Patients who do not tolerate administration of inhaled bronchodilators (e.g., salbutamol).
  13. Patients with life-expectancy of less than 6 months.
  14. Treatments with other Investigational Medicinal Products (IMPs) or previous therapies within four weeks or five times half-life of the drug, whichever is longer prior to screening and during the study. Participation in registries, considering the before, is allowed.
  15. Psychiatric disorders or altered mental status precluding understanding of the informed consent process and/or completion of the necessary procedures.
  16. 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.
  17. Pre-scheduled hospitalizations, surgeries or interventions planned to be performed after obtaining Informed Consent for this study.

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): NCT04107675


Contacts
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Contact: Stefanie Prante +49 89 90405279 stefanie.prante@zambongroup.com

Locations
Show Show 19 study locations
Sponsors and Collaborators
Breath Therapeutics Inc.
Investigators
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Study Director: Noreen R Henig, MD Breath Therapeutics - a Zambon Company

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Responsible Party: Breath Therapeutics Inc.
ClinicalTrials.gov Identifier: NCT04107675    
Other Study ID Numbers: BT - L-CsA - 201 - SCT
First Posted: September 27, 2019    Key Record Dates
Last Update Posted: March 18, 2020
Last Verified: March 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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
Cyclosporine
Cyclosporins
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