liposomal cyclosporine A (LiCsA) / Zambon - LARVOL DELTA

Extension Trial on Efficacy / Safety of L-CsA + SoC in Treating BOS in Post Single or Double Lung Transplant (BOSTON-3) (clinicaltrials.gov) - P3 | N=262 | Active, not recruiting | Sponsor: Zambon SpA | Enrolling by invitation ➔ Active, not recruiting | Trial completion date: Sep 2024 ➔ Dec 2025 | Trial primary completion date: Sep 2024 ➔ Dec 2025

Enrollment closed • Trial completion date • Trial primary completion date • Pulmonary Disease • Respiratory Diseases • Transplantation

Efficacy + Safety of Liposome Cyclosporine a to Treat Bronchiolitis Obliterans Post Single Lung Transplant (BOSTON-1) (clinicaltrials.gov) - P3 | N=220 | Completed | Sponsor: Zambon SpA | Active, not recruiting ➔ Completed | Trial completion date: Nov 2024 ➔ Apr 2024

Trial completion • Trial completion date • Immunology • Pulmonary Disease • Respiratory Diseases • Transplant Rejection • Transplantation

Efficacy + Safety of Liposome Cyclosporine a to Treat Bronchiolitis Obliterans Post Single Lung Transplant (BOSTON-2) (clinicaltrials.gov) - P3 | N=220 | Completed | Sponsor: Zambon SpA | Active, not recruiting ➔ Completed | Trial completion date: Oct 2024 ➔ Mar 2024

Trial completion • Trial completion date • Immunology • Pulmonary Disease • Respiratory Diseases • Transplant Rejection • Transplantation

Efficacy + Safety of Liposome Cyclosporine A to Treat Bronchiolitis Obliterans Post Single Lung Transplant (BOSTON-2) (clinicaltrials.gov) - P3 | N=220 | Active, not recruiting | Sponsor: Zambon SpA | Recruiting ➔ Active, not recruiting | N=152 ➔ 220 | Trial completion date: Sep 2023 ➔ Oct 2024 | Trial primary completion date: Aug 2023 ➔ Apr 2024

Enrollment change • Enrollment closed • Trial completion date • Trial primary completion date • Immunology • Pulmonary Disease • Respiratory Diseases • Transplant Rejection • Transplantation

Efficacy + Safety of Liposome Cyclosporine A to Treat Bronchiolitis Obliterans Post Single Lung Transplant (BOSTON-1) (clinicaltrials.gov) - P3 | N=220 | Active, not recruiting | Sponsor: Zambon SpA | Recruiting ➔ Active, not recruiting | N=110 ➔ 220 | Trial completion date: Jun 2024 ➔ Nov 2024

Enrollment change • Enrollment closed • Trial completion date • Immunology • Pulmonary Disease • Respiratory Diseases • Transplant Rejection • Transplantation

A Safety Study of Liposomal Cyclosporine A to Treat Bronchiolitis After Hematopoietic Transplant (BOSTON-4) (clinicaltrials.gov) - P2a | N=6 | Terminated | Sponsor: Zambon SpA | Trial completion date: Sep 2022 ➔ Dec 2022 | Active, not recruiting ➔ Terminated; 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.

Trial completion date • Trial termination • Bone Marrow Transplantation • Chronic Graft versus Host Disease • Graft versus Host Disease • Immunology • Pulmonary Disease • Respiratory Diseases • Transplantation

A randomized controlled trial of liposomal cyclosporine A for inhalation in the prevention of bronchiolitis obliterans syndrome following lung transplantation. (PubMed, Am J Transplant) - "L-CsA-i inhalation was well tolerated. Although this study failed to meet its primary endpoint, the results warrant additional investigation of L-CsA-i in lung transplant recipients."

Clinical • Journal • Pulmonary Disease • Respiratory Diseases • Transplantation

A Safety Study of Liposomal Cyclosporine A to Treat Bronchiolitis After Hematopoietic Transplant (BOSTON-4) (clinicaltrials.gov) - P2a | N=6 | Active, not recruiting | Sponsor: Zambon SpA | Recruiting ➔ Active, not recruiting | N=24 ➔ 6 | Trial completion date: Apr 2022 ➔ Sep 2022

Enrollment change • Enrollment closed • Trial completion date • Bone Marrow Transplantation • Chronic Graft versus Host Disease • Graft versus Host Disease • Immunology • Pulmonary Disease • Respiratory Diseases • Transplantation

Efficacy + Safety of Liposome Cyclosporine A to Treat Bronchiolitis Obliterans Post Single Lung Transplant (BOSTON-2) (clinicaltrials.gov) - P3 | N=152 | Recruiting | Sponsor: Zambon SpA | N=110 ➔ 152 | Trial primary completion date: Apr 2023 ➔ Aug 2023

Enrollment change • Trial primary completion date • Immunology • Pulmonary Disease • Respiratory Diseases • Transplant Rejection • Transplantation

Efficacy + Safety of Liposome Cyclosporine A to Treat Bronchiolitis Obliterans Post Single Lung Transplant (BOSTON-1) (clinicaltrials.gov) - P3 | N=110 | Recruiting | Sponsor: Zambon SpA | Trial completion date: Jul 2023 ➔ Jun 2024 | Trial primary completion date: Apr 2023 ➔ Jun 2024

Trial completion date • Trial primary completion date • Immunology • Pulmonary Disease • Respiratory Diseases • Transplant Rejection • Transplantation

Extension Trial on Efficacy / Safety of L-CsA + SoC in Treating BOS in Post Single or Double Lung Transplant (BOSTON-3) (clinicaltrials.gov) - P3 | N=262 | Enrolling by invitation | Sponsor: Zambon SpA | Trial completion date: Apr 2024 ➔ Sep 2024 | Trial primary completion date: Mar 2024 ➔ Sep 2024

Trial completion date • Trial primary completion date • Pulmonary Disease • Respiratory Diseases • Transplantation

A Safety Study of Liposomal Cyclosporine A to Treat Bronchiolitis After Hematopoietic Transplant (BOSTON-4) (clinicaltrials.gov) - P2a | N=24 | Recruiting | Sponsor: Zambon SpA | Trial primary completion date: Jan 2022 ➔ Apr 2022

Trial primary completion date • Bone Marrow Transplantation • Chronic Graft versus Host Disease • Graft versus Host Disease • Immunology • Pulmonary Disease • Respiratory Diseases • Transplantation

BOSTON-1: 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 Single Lung Transplant (clinicaltrials.gov) - P3; N=110; Recruiting; Sponsor: Breath Therapeutics Inc.; Trial completion date: Jan 2022 ➔ Jul 2023; Trial primary completion date: Dec 2021 ➔ Apr 2023

Clinical • Trial completion date • Trial primary completion date • Immunology • Respiratory Diseases • Transplantation

BOSTON-2: 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 (clinicaltrials.gov) - P3; N=110; Recruiting; Sponsor: Breath Therapeutics Inc.; Trial completion date: Oct 2021 ➔ Jul 2023; Trial primary completion date: Sep 2021 ➔ Apr 2023

Clinical • Trial completion date • Trial primary completion date • Immunology • Respiratory Diseases • Transplantation

BOSTON-4: A Safety Study of Liposomal Cyclosporine A to Treat Bronchiolitis Obliterans Syndrome Following Allogeneic Hematopoietic Stem Cell Transplant (clinicaltrials.gov) - P2a; N=24; Recruiting; Sponsor: Breath Therapeutics Inc.; Trial completion date: Jan 2021 ➔ May 2022; Trial primary completion date: Dec 2020 ➔ Jan 2022

Clinical • Trial completion date • Trial primary completion date • Graft versus Host Disease • Immunology • Respiratory Diseases • Transplantation

BOSTON-3: Open-Label, Extension Trial to Demonstrate the Effectiveness and Safety of L-CsA Plus Standard of Care in the Treatment of BOS in Patients Post Single or Double Lung Transplant (clinicaltrials.gov) - P3; N=220; Enrolling by invitation; Sponsor: Breath Therapeutics Inc.; Trial completion date: Apr 2023 ➔ Apr 2024; Trial primary completion date: Mar 2023 ➔ Mar 2024

Clinical • Trial completion date • Trial primary completion date • Respiratory Diseases • Transplantation

Methodological considerations for and validation of the ultrasonographic determination of human skeletal muscle hypertrophy and atrophy. (PubMed, Physiol Rep) - "Bland-Altman analysis revealed minimal bias in US measurements relative to the MRI (-0.5 ± 3.0%) and all measurements were within the upper and lower limits of agreement. Our data suggest that B-mode ultrasonography can be a suitable alternative to MRI for measuring changes in muscle size in response to increased and decreased muscle loading in young men."

Journal

Asymmetric atrophy of the multifidus in persons with hemiplegic presentation post-stroke. (PubMed, Top Stroke Rehabil) - "The comparison between the less chronic and chronic phases suggested that the recovery pattern of the trunk muscles could differ between sides in unilateral hemiplegia: increased size of the multifidus, a tonic stabilizer, on the less-affected side and of the erector spinae, a phasic muscle, on the more-affected side. This finding could be applied to trunk rehabilitation strategies for persons post-stroke."

Journal • Cardiovascular • MRI

Cyclosporine A for the Prevention of Ocular Graft versus Host Disease in Allogeneic Hematopoietic Stem Cell Transplant Recipients Is Safe and Feasible. (PubMed, Acta Haematol) - "Topical CsA as a prophylactic measure for oGVHD, administered over a period of 1 year after grafting, is safe and feasible and may decrease the incidence of ophthalmic manifestations of GVHD. These findings must be confirmed in a randomized trial."

Clinical • Journal • Graft versus Host Disease • Ophthalmology • Transplantation

Retrospective Analysis and Systematic Review of Isolated Traumatic Dissections of the Celiac Artery. (PubMed, Ann Vasc Surg) - "Traumatic CA dissections are mostly caused by traffic accidents and falls. Visceral perfusion should be monitored clinically and radiologically. Beginning visceral ischemia requires early invasive treatment. Endovascular and open surgery are possible options. Benefits of specific pharmaceuticals are still up for debate. Follow-up via magnetic resonance imaging or computed tomography angiography is essential to rule out vascular complications."

Journal • Retrospective data • Review • Hepatology • Liver Failure • Mood Disorders

Annexin V in children with idiopathic nephrotic syndrome treated with cyclosporine A. (PubMed, Adv Clin Exp Med) - "The increased urinary excretion of AnV in children with INS receiving CsA treatment may suggest its usefulness as an early marker of subclinical CsAN. Annexin V seems to be a more sensitive indicator of tubular damage in the course of CsA therapy than UM, though large, multicenter studies are needed."

Clinical • Journal • Glomerulonephritis • Nephrology • Renal Disease

[VIRTUAL] TRANSVENOUS PHRENIC NERVE STIMULATION IMPACT ON PATIENTS WITH HEART FAILURE AND CENTRAL SLEEP APNEA (CHEST 2020) - "The results of this RCT suggest in patients with HF and CSA, TPNS significantly improves sleep metrics and QoL independent of ESS. Additionally, TPNS improves EDS significantly in the subgroup with EDS≥8, suggesting ESS≥8 may be a better threshold defining EDS as it identifies a subgroup of HF patients who may benefit most from TPNS therapy in sleepiness and QoL. Similar data with CPAP or ASV are lacking but could be retrieved from previous RCTs which reported no significant change in EDS."

Clinical • Cardiovascular • Congestive Heart Failure • Heart Failure • Obstructive Sleep Apnea • Sleep Apnea • Sleep Disorder

[VIRTUAL] Pediatric Patients with Bronchiolitis Obliterans Syndrome (BOS): Dosing and Breath Simulation Experiments of Liposomal Cyclosporin A for Inhalation (L-CsA-i) (ATS-I 2020) - "The DD and RD shown in this study support the dosing strategy employed in the BOSTON-5 clinical study, with 5 mg bid in children aged 6-11 years as an exception to the standard 10 mg bid dose. These results are dependent on use of the optimized drug-specific nebulizer used with L-CsA-i."

Clinical • Pediatrics • Respiratory Diseases • Transplantation

Oral fluid intake during the first stage of labour: A randomised trial. (PubMed, Eur J Anaesthesiol) - P=N/A | "The current study reveals that the percentage of pregnant women with an 'empty stomach', defined by an antral CSA less than 300 mm in a semirecumbent position with a 45-degree head-up tilt, was comparable at full cervical dilation among those who remained nil by mouth and those allowed to drink up to 400 ml for 90 min after their randomisation."

Clinical • Journal • Anesthesia

Genome-wide identification and characterization of ALTERNATIVE OXIDASE genes and their response under abiotic stresses in Camellia sinensis (L.) O. Kuntze. (PubMed, Planta) - "...Gene structure and protein sequence analyses revealed that all CsAOXs share a four-exon/three-intron structure with highly conserved regions and amino acid residues, which are necessary for AOX secondary structures, catalytic activities and post-translational regulations...These results suggest a link between CsAOX1a function and the metabolism of some secondary metabolites in tea plant. Our studies provide a basis for the further elucidation of the biological function and regulation of the AOX pathway in tea plants."

Journal • Biosimilar