Extension Trial on Efficacy / Safety of L-CsA + SoC in Treating BOS in Post Single or Double Lung Transplant (BOSTON-3)

Bronchiolitis Obliterans Clinical Trial

— 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

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT04039347
• Other study ID #: BT - L-CsA - 303 - FU
• Secondary ID: 2019-002987-29
• Status: Enrolling by invitation
• Phase: Phase 3
• Start date: March 12, 2020
• Est. completion date: September 2024

Study information

• Verified date: October 2023
• Source: Zambon SpA
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 262
• Est. completion date: September 2024
• Est. primary completion date: September 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Bronchiolitis
• Bronchiolitis Obliterans
• Bronchiolitis Obliterans Syndrome
• Obliterative Bronchiolitis

Intervention

Drug:
• Liposomal Cyclosporine A 5 mg
delivered via the PARI eFlow® device, which is a new technology of nebulizing liquid drugs with a perforated vibrating membrane resulting in an aerosol with a low ballistic momentum and a high percentage of droplets in a respirable size range of 3-5 µm
• Liposomal Cyclosporine A 10 mg
delivered via the PARI eFlow® device, which is a new technology of nebulizing liquid drugs with a perforated vibrating membrane resulting in an aerosol with a low ballistic momentum and a high percentage of droplets in a respirable size range of 3-5 µm

Locations

Country	Name	City	State
Austria	Waehringer Guertel	Vienna
Belgium	Hôpital Erasme	Brussel
Belgium	Universitair Ziekenhuis Leuven	Leuven
Denmark	Copenhagen University Hospital	Copenhagen
France	Hopital Marie Lannelongue	Le Plessis-Robinson
France	CHU Hopital Nord	Marseille
France	Hopitaux Universitaires de Strasbourg	Strasbourg
Germany	Hannover Medical School	Hannover
Germany	LMU Klinikum Groshadern	Munich
Israel	Rabin Medical Center	Petah tikva
Spain	Complexo Hospitalario de A Coruna	A Coruña
Spain	Hospital Universitari Vall d'Hebron	Barcelona
Spain	Hospital Universitario Puerta de Hierro - Unidad de Trasplante Pulmonar	Madrid
Spain	Hospital Marques de Valdecilla	Santander
Spain	Unidad de Trasplante Pulmonar del Hospital La Fe	Valencia
United Kingdom	Royal Papworth Hospital NHS Foundation Trust	Cambridge
United Kingdom	University of Manchester	Manchester
United States	Johns Hopkins University Hospital	Baltimore	Maryland
United States	University of Maryland	Baltimore	Maryland
United States	Cleveland Clinic	Cleveland	Ohio
United States	OSU Wexner Medical Center	Columbus	Ohio
United States	Baylor University Medical Center	Dallas	Texas
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	Duke University	Durham	North Carolina
United States	University of Florida Dept of Pulmonary Medicine	Gainesville	Florida
United States	Baylor College of Medicine	Houston	Texas
United States	Houston Methodist Hospital	Houston	Texas
United States	Indiana University	Indianapolis	Indiana
United States	UK Albert B. Chandler Hospital	Lexington	Kentucky
United States	David Geffen School of Medicine at UCLA	Los Angeles	California
United States	Columbia University Medical Center	New York	New York
United States	Temple University Hospital	Philadelphia	Pennsylvania
United States	Banner - University Medical Center	Phoenix	Arizona
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	Barnes-Jewish Hospital	Saint Louis	Missouri
United States	UCSF	San Francisco	California
United States	UCSF Center for Advanced Lung Disease	Stanford	California

Sponsors (1)

Lead Sponsor	Collaborator
Zambon SpA

Countries where clinical trial is conducted

United States,  Austria,  Belgium,  Denmark,  France,  Germany,  Israel,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Adverse events	An untoward medical occurrence after exposure to a medicine, which is not necessarily caused by that medicine.	Baseline through end of study, approximately 2 years
Other	Acute tolerability of L-CsA as measured by change in FEV1 at 1 hour and 4 hours after first inhalation of L-CsA	Parameters reflecting acute tolerability of IMP are: spirometry, before and 1 hour and 4 hours after inhalation of L-CsA at initial dosing.; cough, or; dyspnea.	First treatment with L-CsA
Other	Acute tolerability of L-CsA as measured by number of patients with treatment-related adverse events	Acute tolerability of L-CsA is measured by number of patients with treatment-related adverse events as assessed by CTCAE v5.0	Baseline through end of treatment, approximately 2 years
Other	Number of patients with treatment-related changes in hematology or serum chemistry parameters	Number of patients with treatment-related changes in hematology or serum chemistry parameters assessed by CTCAE v5.0	Baseline through end of study participation, approximately 2 years
Primary	Mean change in FEV1 from Baseline to Week 24	FEV1 is the Forced Expiratory Volume in One Second	Baseline to Week 24
Secondary	Mean change in FEV1 from Baseline to Week 48	FEV1 is the Forced Expiratory Volume in One Second	Baseline to Week 48
Secondary	Mean change in FEV1 from Baseline to End of Study	FEV1 is the Forced Expiratory Volume in One Second	Baseline to end of study, approximately 2 years
Secondary	Mean change in FEV1/FVC from Baseline to Week 24	FEV1/FVC is the ratio between Forced Expiratory Volume in One Second and Forced Vital Capacity.	Baseline to Week 24
Secondary	Mean change in FEV1/FVC from Baseline to Week 48	FEV1/FVC is the ratio between Forced Expiratory Volume in One Second and Forced Vital Capacity.	Baseline to Week 48
Secondary	Time to Progression of BOS	The Progression of BOS is defined as the earliest of: Absolute decrease from baseline in FEV1 >/= 10% or >/= 200 mL and absolute decrease in FEV1/FVC of > 5%, OR; Change in BOS severity (according to criteria in Verleden 2019), OR; Re-transplantation, OR; Death from respiratory failure	Baseline to End of Study, approximately 2 years