A6. A006 HOT TAKES FROM CLINICAL TRIALS IN LUNG DISEASE最新文献

{"title":"Effect of Nintedanib on Decline in Forced Vital Capacity (FVC) in Patients with Progressive Fibrosing Interstitial Lung Diseases (ILDs) by GAP Stage","authors":"C. Ryerson, N. Chaudhuri, E. F. Fernández Pérez, Y. Kim, R.S. Silva, W. Wuyts, H. Müller, K. Rohr, M. Kolb","doi":"10.1164/ajrccm-conference.2021.203.1_meetingabstracts.a1026","DOIUrl":"https://doi.org/10.1164/ajrccm-conference.2021.203.1_meetingabstracts.a1026","url":null,"abstract":"","PeriodicalId":403254,"journal":{"name":"A6. A006 HOT TAKES FROM CLINICAL TRIALS IN LUNG DISEASE","volume":"29 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"117246425","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-Term Follow-up of Severe Emphysema Patients Treated with Zephyr Valves in the Multicenter, Randomized TRANSFORM Study","authors":"D. Slebos, M. Kornaszewska, S. Kemp, A. Kirk, K. Carron, H. Mal, C. Pison, N. Downer, K. Darwiche, J. Rao, Ralph-Harto Hubner, V. Trosini-Desert, R. Eberhardt, E. Derom, C. Marquette, N. Shargill, P. Shah","doi":"10.1164/ajrccm-conference.2021.203.1_meetingabstracts.a1023","DOIUrl":"https://doi.org/10.1164/ajrccm-conference.2021.203.1_meetingabstracts.a1023","url":null,"abstract":"","PeriodicalId":403254,"journal":{"name":"A6. A006 HOT TAKES FROM CLINICAL TRIALS IN LUNG DISEASE","volume":"8 13 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"124909847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Improvements in Cough Frequency Over 24 Hours with BLU-5937, a Selective P2X3 Antagonist, in Patient Subgroups Defined by Baseline Awake Cough Frequencies","authors":"J. Smith, A. Morice, S. Birring, S. Parker, P. Marsden, J. Holcomb, B. Prenner, M. Sher, G. Steven, L. Mcgarvey, D. Garceau, C. Bonuccelli, L. Harvey","doi":"10.1164/ajrccm-conference.2021.203.1_meetingabstracts.a1019","DOIUrl":"https://doi.org/10.1164/ajrccm-conference.2021.203.1_meetingabstracts.a1019","url":null,"abstract":"","PeriodicalId":403254,"journal":{"name":"A6. A006 HOT TAKES FROM CLINICAL TRIALS IN LUNG DISEASE","volume":"223 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"123400837","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety and Tolerability Demonstrated with Inhaled αENaC Antisense Oligonucleotide (ION-827359) in Patients with Cystic Fibrosis","authors":"K. Newman, R. Fischer, S. Sutharsan, W. Gleiber, A. Horsley, D. Bell, J. Elborn","doi":"10.1164/ajrccm-conference.2021.203.1_meetingabstracts.a1020","DOIUrl":"https://doi.org/10.1164/ajrccm-conference.2021.203.1_meetingabstracts.a1020","url":null,"abstract":"Background: Epithelial sodium channels (ENaC) have been demonstrated to be hyperactive in patients with Cystic Fibrosis (CF) and to contribute to reduced airway surface liquid, mucus dehydration and airway mucus accumulation. An antisense oligonucleotide (ASO) which inhibits murine αENaC expression was demonstrated to be efficacious in two different mouse models of CF. ION-827359 is a chemically modified ASO, 16 nucleotides in length with a phosphorothioate backbone and constrained ethyl (cEt) modifications. In healthy volunteers the ASO was found to decrease ENaC mRNA expression in bronchial brushings by a mean of 56%.Methods: This ascending dose trial was conducted in three parts, the first two of which were in healthy volunteers. The third part of this trial was a randomized, double-blind, placebo-controlled multiple ascending dose (MAD) study in patients with CF. Patients were allowed to stay on their usual CF medications throughout the trial. The primary objective was the evaluation of safety and pharmacokinetics of ION-827359 delivered via a Pari eFlow © mesh nebulizer. A total of 33 subjects in 4 cohorts received doses of 10, 37.5, 75, or 100 mg once weekly for 4 doses, with an additional dose administered during the first week. Subjects were followed for 13 weeks after dosing. Results: ION-827359 was well-tolerated with an acceptable safety profile after multiple inhalations. The rate of adverse events was similar between ION-827359 and placebo treated groups. There were no clinically relevant changes in chemistry, hematology, urinalysis, ECG, or vital signs. There were no drug related serious adverse events or discontinuations due to adverse events although three subjects discontinued early due to concerns about COVID-19. Pharmacokinetics demonstrated low systemic exposure with a plasma half-life of approximately 2 weeks. Spirometry showed a numerical dose dependent increase in FEV1 at the end of the 4-week treatment period (4.5% difference for 100mg group from placebo). Conclusions: These results demonstrate strong evidence of tolerability and safety at the doses and regimens tested and supports further investigation of ENaC ASO ION-827359 in patients with cystic fibrosis.","PeriodicalId":403254,"journal":{"name":"A6. A006 HOT TAKES FROM CLINICAL TRIALS IN LUNG DISEASE","volume":"42 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"132592635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combination Therapy Trials for Scleroderma-Related Interstitial Lung Disease: Initial and Adaptive Trial Aspects of Scleroderma Lung Study III in the Setting of a Rapidly Changing Clinical Environment","authors":"M. Roth, D. Khanna, D. Tashkin, E. Bernstein, C. Spino, Scleroderma Lung Study III Investigators","doi":"10.1164/ajrccm-conference.2021.203.1_meetingabstracts.a1024","DOIUrl":"https://doi.org/10.1164/ajrccm-conference.2021.203.1_meetingabstracts.a1024","url":null,"abstract":"RATIONALE: Scleroderma Lung Study (SLS) II established mycophenolate mofetil (MMF) as an active therapy for scleroderma-related interstitial lung disease (SSc-ILD) and the need to consider background MMF in future study designs. SLS III envisioned combination therapy in which the rapid onset and anti-fibrotic effects of pirfenidone (PFD) would complement the delayed immunosuppressive/anti-inflammatory actions of MMF. However, the study design failed to adequately predict the impact from widespread use of MMF by community physicians or FDA approval of nintedanib (9/19) to slow pulmonary function decline in SSc-ILD. SLS III recruitment challenges and adaptive clinical trial modifications are presented. METHODS: SLS III is an investigator-initiated, multi-center, double-blind placebo-controlled Phase II clinical trial of PFD in SSc-ILD. 150 treatment-naive patients were to be randomized to PFD or placebo, along with initiating MMF, to determine the relative efficacy/safety of combination therapy to MMF alone. The primary endpoint is change from baseline in FVC-% predicted during the 18-month treatment. Three adaptations were implemented: relaxation of screening/entry criteria;expansion of participating clinical sites and enrollment period;and a shift in the target population to include those already receiving MMF. RESULTS: At study initiation (01/18), recruiting eligible treatment-naive patients was already identified as a challenge. The maximum allowed FVC-% at screening (80%) and minimum allowed DLCO-% at baseline (25%) were relaxed 5% to reduce screen failures. The definition of “treatmentnaive” was broadened to include <3 months of prior MMF without need for a washout. With the release of SENSCIS results (05/20), we increased the number of clinical sites and the recruitment period. However, the rapid adoption of MMF therapy as a community standard forced us to consider patients already on longer treatment with MMF. The time-dependent impact of prior MMF duration on treatment effect was explored using clinical trial simulations to assess study power (Fig 1) and prior MMF exposure stratified into groups (naïve;<3, >3-6 and >6-9 months). The data identified an acceptable power (0.80) if <50% of enrolled participants had prior MMF use and prior MMF exposure was capped at 6 months (i.e., 3 groups). Unfortunately, the impact from COVID-19 ultimately curtailed site expansion and led to a truncated recruiting period (10/1/2020). 51 participants were randomized (76% naive;14% <3 months MMF;10% >3-6 months MMF). CONCLUSIONS: The SLS III experience highlights challenges in designing treatment protocols for SSc-ILD and the application of background study data and clinical trial simulations to execute adaptive study changes. (Table Presented).","PeriodicalId":403254,"journal":{"name":"A6. A006 HOT TAKES FROM CLINICAL TRIALS IN LUNG DISEASE","volume":"13 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"114960633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tocilizumab in Systemic Sclerosis Interstitial Lung Disease: Safety and Efficacy in the Double-Blind and Open-Label Periods of a Randomized Controlled Phase 3 Trial","authors":"D. Khanna, C. Lin, D. Furst, M. Zucchetto, G. Raghu, F. J. Martínez, C. Denton","doi":"10.1164/ajrccm-conference.2021.203.1_meetingabstracts.a1025","DOIUrl":"https://doi.org/10.1164/ajrccm-conference.2021.203.1_meetingabstracts.a1025","url":null,"abstract":"","PeriodicalId":403254,"journal":{"name":"A6. A006 HOT TAKES FROM CLINICAL TRIALS IN LUNG DISEASE","volume":"64 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"124193285","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endoscopic Lung Volume Reduction with Endobronchial Valves in Patients with Hypercapnia: Results of a Prospective Observational Clinical Study","authors":"P. Lenga, C. Grah, C. Ruwwe-Glösenkamp, J. Saccomanno, J. Pfannschmidt, S. Eggeling, S. Gläser, S. Kurz, G. Leschber, J. Rückert, B. Schmidt, P. Schneider, A. Gebhardt, B. Becke, O. Schega, A. Holland, A. Kirschbaum, S. Eisenmann, M. Krüger, R. Hübner","doi":"10.1164/ajrccm-conference.2021.203.1_meetingabstracts.a1022","DOIUrl":"https://doi.org/10.1164/ajrccm-conference.2021.203.1_meetingabstracts.a1022","url":null,"abstract":"","PeriodicalId":403254,"journal":{"name":"A6. A006 HOT TAKES FROM CLINICAL TRIALS IN LUNG DISEASE","volume":"16 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"133397930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}