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Bronchiolitis Obliterans Syndrome (BOS)Phase 2BOSTON-4NCT04107675

A Safety Study of Liposomal Cyclosporine A to Treat Bronchiolitis After Hematopoietic Transplant (BOSTON-4)

A Phase 2 study testing Liposomal Cyclosporine A in people with Bronchiolitis Obliterans Syndrome (BOS) and GVHD, Chronic, run by Zambon SpA at 17 sites in 3 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

Primary Objective: The primary objective of this study is to assess the tolerability and safety of two dose levels of aerosolized L-CsA vs placebo in addition to SoC therapy for BOS in adult allo-HSCT recipients. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Liposomal Cyclosporine A
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
6 participants
Where
17 sitesin 3 countries
Study dates
11 Feb 2020to 15 Dec 2022
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Age >/= 18 years
  • Patient must have a history of allogeneic HSCT, regardless of source of stem cell or donor or indication for allogeneic HSCT
  • 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.
  • 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.
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  • 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.
  • Patient is capable of aerosol inhalation.
  • Women of childbearing potential must have a negative serum or urine pregnancy test at screening and at randomization visit.

Who cannot join

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

Trial locations and contacts

17 sites in 3 countries.

17 sites in 3 countries

France8 sites
  • CHU Hôpital Sud

    Amiens

  • Centre Hospitalier Universitaire d'Angers

    Angers

  • Centre Hospitalier Universitaire Grenoble Alpes - Hopital Albert Michallon

    La Tronche

  • Centre Hospitalier Régional Universitaire de Lille (CHRU) - Hôpital Claude Huriez

    Lille

  • CHU de Nancy, Hopital Brabois

    Nancy

  • CHU de Nantes - Hotel-Dieu

    Nantes

  • Hopital Saint Louis

    Paris

  • CHU Hopitaux de Bordeaux - Hôpital Haut-Lévêque

    Pessac

Other trials in France

Spain5 sites
  • Hospital Clinic i Provincial

    Barcelona

  • Hospital de la Santa Creu i Sant Pau

    Barcelona

  • Hospital Universitario Ramón y Cajal

    Madrid

  • Hospital Clinico Universitario de Valencia

    Valencia

  • Hospital Universitari i Politècnic La Fe

    Valencia

Other trials in Spain

Germany4 sites
  • Universitätsklinikum Köln

    Cologne

  • St.-Johannes-Hospital

    Dortmund

  • Universitätsklinikum Carl Gustav Carus

    Dresden

  • Universitätsklinikum Münster

    Münster

Other trials in Germany

About this study

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

Primary Objective:

The primary objective of this study is to assess the tolerability and safety of two dose levels of aerosolized L-CsA vs placebo in addition to SoC therapy for BOS in adult allo-HSCT recipients.

Secondary Objectives:

The secondary objectives of this study are to assess PK and exploratory efficacy and quality of life of two dose levels of aerosolized L-CsA vs placebo in addition to SoC therapy for BOS in adult allo-HSCT recipients.

Read the detailed description

This is a Phase II prospective, multi-center, single-blind, randomized clinical trial evaluating safety and tolerability in adult recipients of an allo-HSCT with BOS. Twenty-four patients were planned for enrollment; but, at the time of the premature termination of this study, a total of 11 patients were screened for the study, of whom 5 patients did not fulfill the inclusion criteria and 6 patients were randomly allocated 1:1:1 in 3 treatment groups (L-CsA 10 mg + SoC, L-CsA 5 mg + SoC, or placebo + SoC).

A total of 18 centers in 3 countries (France, Germany, and Spain) in Europe were initiated for this multi-center study.

IMP was administered for up to 12 weeks treatment period. With low patient recruitment, the BOSTON-4 safety and tolerability study was terminated early by the sponsor on 18 March 2022. This decision was made after a careful and due diligent analysis performed by Zambon of the study status and considering the impact of coronavirus disease 2019 (COVID-19) pandemic on sites activities. From the beginning of the study, in December 2019, only 6 patients were randomized. So it was estimated that continuing the trial with the current protocol and setting would have taken another 9 years for the study to complete.

Being tested
Liposomal Cyclosporine A, Liposomal Placebo
Keywords
stem cell, hematopoietic transplant
Medical subject headings
Bronchiolitis Obliterans Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Liposomal Cyclosporine ADrug

    Also called L-CsA

    Liposomal Cyclosporine A is administered at different dosages in the first two arms (10 mg bid and 5 mg bid, respectively) with a new technology of nebulizing liquid drugs, creating an aerosol with a low ballistic momentum and a high percentage of droplets in a respirable size range of 3-5 μm

  • Liposomal PlaceboDrug

    Also called Placebo

    Liposomal Placebo is administered with the same new technology of nebulizing liquid drugs used for L-CsA, creating an aerosol with a low ballistic momentum and a high percentage of droplets in a respirable size range of 3-5 μm

Study groups in NCT04107675
Study groupRoleWhat they receive
L-CsA 10 mg plus Standard of CareExperimentalLiposomal Cyclosporine A 10 mg (10 mg/2.5 mL) bid, once in the morning and once in the evening, for up to 12 weeks. The inhalations were scheduled to be taken approximately 12 hours (but not less than 6 hours) apart, eg, at 08:00 and 20:00 each day. Nebulization time per inhalation dose was approximately 8 to 13 minutes for the 0- and 10-mg doses. Standard of care included prophylaxis against common opportunistic infections, immunosuppression, and any other chronic medication
Receives: Drug: Liposomal Cyclosporine A
L-CsA 5 mg plus Standard of CareExperimentalLiposomal Cyclosporine A 5 mg (5 mg/1.25 mL) bid, once in the morning and once in the evening, for up to 12 weeks. The inhalations were scheduled to be taken approximately 12 hours (but not less than 6 hours) apart, eg, at 08:00 and 20:00 each day. Nebulization time per inhalation dose was approximately 5 to 10 minutes for the 5-mg dose. Standard of care included prophylaxis against common opportunistic infections, immunosuppression, and any other chronic medication
Receives: Drug: Liposomal Cyclosporine A
Liposomal Placebo plus Standard of CarePlacebo comparatorLiposomal Placebo 2.5 mL (0 mg L-CsA/2.5 mL) bid, once in the morning and once in the evening, for up to 12 weeks. The inhalations were scheduled to be taken approximately 12 hours (but not less than 6 hours) apart, eg, at 08:00 and 20:00 each day. Nebulization time per inhalation dose was approximately 8 to 13 minutes for the 0- and 10-mg doses. Standard of care included prophylaxis against common opportunistic infections, immunosuppression, and any other chronic medication
Receives: Drug: Liposomal Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Local Tolerability Events of Interest From Baseline to Visit 3 (Week 4)

    The local tolerability events of interest taken into consideration were: Cough, Wheezing, Bronchospasm, Throat irritation and Change from baseline in FEV1 to Visit 3.

    Measured: at Week 4 (visit 3)

  2. Number of Participants With AE and sAE of Different Level of Severity During the First 4 Weeks of Treatment

    An adverse event (AE) is any untoward medical occurrence after exposure to a medicine, which is not necessarily caused by that medicine. An adverse event can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.

    A serious adverse event is an adverse event that results in death, is life-threatening, requires hospitalisation or prolongation of existing hospitalisation, results in persistent or significant disability or incapacity, or is a birth defect.

    Measured: During the first 4 weeks of treatment

Secondary outcomes (3)
  1. Number of Local Tolerability Events of Interest From Baseline to Week 12

    The local tolerability events of interest taken into consideration were: Cough, Wheezing, Bronchospasm, Throat irritation and Change from baseline in FEV1 to Visit 3.

    Measured: at Week 12

  2. Number of Participants With AE and sAE of Different Level of Severity During the First 12 Weeks of Treatment

    An adverse event (AE) is any untoward medical occurrence after exposure to a medicine, which is not necessarily caused by that medicine. An adverse event can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.

    A serious adverse event is an adverse event that results in death, is life-threatening, requires hospitalisation or prolongation of existing hospitalisation, results in persistent or significant disability or incapacity, or is a birth defect.

    Measured: During the first 12 weeks of treatment

  3. CsA Whole Blood Concentrations and CsA Whole Blood Trough Levels

    Whole Blood concentrations (Week 0) are at pre-dose, directly after end of inhalation, 15, 30, and 45 minutes, and 1, 1.5, 2, and 4 hours after end of inhalation, and whole blood trough levels (CsA concentration) at Weeks 2, 4, 8, and 12 were calculated.

    Measured: Weeks 0 (pre-dose, directly after end of inhalation, 15, 30, 45, 60 min, 1.5 h, 2h, 4h), 2, 4, 8, and 12

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Sep 2019
  2. Study start11 Feb 2020
  3. Primary completion16 Jun 2022
  4. Study completion15 Dec 2022

Why it stopped: Due to the low number of patients recruited and the slow enrollment pace of patients, on 18 March 2022, the sponsor decided to terminate the BOSTON-4 safety and tolerability trial ahead of time.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Single blind
Who is masked
Participant
Enrolment
6 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04107675
Sponsor's protocol ID
BT - L-CsA - 201 - SCT
Other IDs
2019-000718-13, 2019
Acronym
BOSTON-4
Status last verified
Sep 2023
First submitted
25 Sep 2019
Last updated
3 Oct 2023
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Liposomal Cyclosporine A in people with Bronchiolitis Obliterans Syndrome (BOS) and GVHD, Chronic, run by Zambon SpA at 17 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 3 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 17 sites in France, Spain, Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 3 Oct 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Local Tolerability Events of Interest From Baseline to Visit 3 (Week 4) (time frame: at Week 4 (visit 3)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Oct 2023.

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