Clinical trial NCT04039347: Extension Trial on Efficacy / Safety of L-CsA + SoC in Treating BOS in Post Single or Double Lung Transplant (BOSTON-3)
Official title: A Phase III, Extension Clinical Trial to Demonstrate Efficacy and Safety of Liposomal Cyclosprine a Via the PARI Investigational EFlow® Device and SoC in Treating Bronchiolitis Obliterans in Patients Post Single or Double Lung Transplant
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Bronchiolitis Obliterans
Obliterative Bronchiolitis
Bronchiolitis Obliterans Syndrome
Keywords: single and double transplant
Lead sponsor: Zambon SpA
Sponsor class: INDUSTRY
First posted: 2019-07-31
Enrollment: 262
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The objective of the trial is to assess the long-term safety and efficacy of L-CsA plus Standard of Care (SoC) in the treatment of BOS in single (SLT) and double lung transplant (DLT) recipients.

Detailed description: This is a Phase III, multicenter, open-label, extension clinical trial of L-CsA for the treatment of BOS.

Enrollment will be limited to patients who have completed 48 weeks participation in either the BT-L-CsA-301-SLT (BOSTON-1) or BT-L-CsA-302-DLT (BOSTON-2) trial. All patients in this clinical trial will receive L-CsA in addition to SoC, regardless of the randomization arm in prior trials.

IMP will be administered by BID inhalation (morning/evening) using the L-CsA eFlow. Patients who did not receive L-CsA in BOSTON-1 or BOSTON-2 must remain in the clinic for at least 4 hours for observation after the first inhalation. At all subsequent visits, one dose administered via inhalation will be monitored by the clinical trial center personnel. In case patients receiving L-CsA undergo the last visit for BOSTON-1 or BOSTON-2 (Visit 9) on the same day as for Visit 1 for BOSTON-3, they will take the first dose for Boston 3 in the evening of this day. This first dose will not be supervised by the site staff. Nebulization time per inhalation dose is approximately 6-10 minutes for the 5 mg dose and 9-13 minutes for the 10 mg dose. Inhalations will be performed BID approximately 12 hours apart through a mouthpiece by slow and deep respiration using the L-CsA eFlow. A high efficiency particulate air filter is used to prevent environmental contamination during exhalation.

Eligibility criteria: Inclusion Criteria:

1. Patients who have completed all visits through the End of Treatment Visit in either BOSTON-1 or BOSTON-2, did not withdraw informed consent, and did not prematurely terminate study drug administration.
2. Patients should be on a three-drug maintenance regimen of immunosuppressive agents including tacrolimus or another CNI, a second agent such as but not limited to MMF or azathioprine, and a systemic corticosteroid such as prednisone.
3. 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.
4. Women of childbearing potential must have a negative serum pregnancy test within 7 days prior to Visit 1 and must agree to use one of the methods of contraception listed in Appendix II through their End of Study Visit.

Exclusion Criteria:

1. Known hypersensitivity to L-CsA or to cyclosporine A.
2. Patients who experienced an AE related to study drug that led to permanent study drug discontinuation in BOSTON-1 or BOSTON-2.
3. Patients with new onset of malignancy while participating in BOSTON-1 or BOSTON-2, including post-transplant lymphoproliferative disorder, with the exception of treated, localized basal and squamous cell carcinomas.
4. Pregnant women or women who are unwilling to use appropriate birth control to avoid pregnancy through their End of Study Visit.
5. Women who are currently breastfeeding.
6. Receipt of an investigational drug, other than L-CsA, as part of a clinical trial within 4 weeks prior to Visit 1. This is defined as any treatment that is implemented under an Investigational New Drug (IND) or compassionate use.
7. Patients who are currently participating in an interventional clinical trial, other than BOSTON-1 or BOSTON-2.
8. Psychiatric disorders or altered mental status precluding understanding of the informed consent process and/or completion of the necessary procedures.
9. 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.

Primary outcomes:
measure: Mean change in FEV1 from Baseline to Week 24
timeFrame: Baseline to Week 24
Secondary outcomes:
measure: Mean change in FEV1 from Baseline to Week 48
timeFrame: Baseline to Week 48
measure: Mean change in FEV1 from Baseline to End of Study
timeFrame: Baseline to end of study, approximately 2 years
measure: Mean change in FEV1/FVC from Baseline to Week 24
timeFrame: Baseline to Week 24
measure: Mean change in FEV1/FVC from Baseline to Week 48
timeFrame: Baseline to Week 48
measure: Time to Progression of BOS
timeFrame: Baseline to End of Study, approximately 2 years
Other outcomes:
measure: Adverse events
timeFrame: Baseline through end of study, approximately 2 years
measure: Acute tolerability of L-CsA as measured by change in FEV1 at 1 hour and 4 hours after first inhalation of L-CsA
timeFrame: First treatment with L-CsA
measure: Acute tolerability of L-CsA as measured by number of patients with treatment-related adverse events
timeFrame: Baseline through end of treatment, approximately 2 years
measure: Number of patients with treatment-related changes in hematology or serum chemistry parameters
timeFrame: Baseline through end of study participation, approximately 2 years
Locations:
city: Phoenix
country: United States
facility: Banner - University Medical Center
state: Arizona
city: Los Angeles
country: United States
facility: David Geffen School of Medicine at UCLA
state: California
city: San Francisco
country: United States
facility: UCSF
state: California
city: Stanford
country: United States
facility: UCSF Center for Advanced Lung Disease
state: California
city: Gainesville
country: United States
facility: University of Florida Dept of Pulmonary Medicine
state: Florida
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Lexington
country: United States
facility: UK Albert B. Chandler Hospital
state: Kentucky
city: Baltimore
country: United States
facility: University of Maryland
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins University Hospital
state: Maryland
city: Saint Louis
country: United States
facility: Barnes-Jewish Hospital
state: Missouri
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Columbus
country: United States
facility: OSU Wexner Medical Center
state: Ohio
city: Philadelphia
country: United States
facility: Temple University Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Dallas
country: United States
facility: Baylor University Medical Center
state: Texas
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Houston
country: United States
facility: Houston Methodist Hospital
state: Texas
city: Vienna
country: Austria
facility: Waehringer Guertel
city: Brussel
country: Belgium
facility: Hôpital Erasme
city: Leuven
country: Belgium
facility: Universitair Ziekenhuis Leuven
city: Copenhagen
country: Denmark
facility: Copenhagen University Hospital
city: Le Plessis-Robinson
country: France
facility: Hopital Marie Lannelongue
city: Marseille
country: France
facility: CHU Hopital Nord
city: Strasbourg
country: France
facility: Hopitaux Universitaires de Strasbourg
city: Hannover
country: Germany
facility: Hannover Medical School
city: Munich
country: Germany
facility: LMU Klinikum Groshadern
city: Petah tikva
country: Israel
facility: Rabin Medical Center
city: A Coruña
country: Spain
facility: Complexo Hospitalario de A Coruna
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Madrid
country: Spain
facility: Hospital Universitario Puerta de Hierro - Unidad de Trasplante Pulmonar
city: Santander
country: Spain
facility: Hospital Marques de Valdecilla
city: Valencia
country: Spain
facility: Unidad de Trasplante Pulmonar del Hospital La Fe
city: Cambridge
country: United Kingdom
facility: Royal Papworth Hospital NHS Foundation Trust
city: Manchester
country: United Kingdom
facility: University of Manchester
Study officials:
affiliation: Zambon SpA, Chief Medical Officer
name: Paola R Castellani, MD
role: STUDY_DIRECTOR
References: