ATS 2021 will feature presentations of original research from accepted abstracts. Mini Symposia and Thematic Poster Sessions are abstract based sessions.
Please use the form below to browse scientific abstracts and case reports accepted for ATS 2021. Abstracts presented at the ATS 2021 will be published in the Online Abstract Issue of the American Journal of Respiratory and Critical Care Medicine, Volume 203, May 3, 2021.
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A Single-Center, Randomized, Placebo-Controlled Study to Evaluate the Efficacy, Safety, and Tolerability of MN-001 (Tipelukast) in Subjects with Idiopathic Pulmonary Fibrosis
Session Title
TP28 - TP028 APPROACH TO THERAPY IN FIBROSING AND NON-FIBROSING ILD
Abstract
A1898 - A Single-Center, Randomized, Placebo-Controlled Study to Evaluate the Efficacy, Safety, and Tolerability of MN-001 (Tipelukast) in Subjects with Idiopathic Pulmonary Fibrosis
Author Block: R. Bascom1, K. Hitz1, A. E. Dimmock1, M. Makhay2, K. Matsuda2; 1MS Hershey Medical Ctr, Penn State Univ, Hershey, PA, United States, 2MediciNova, La Jolla, CA, United States.
BACKGROUND
Idiopathic pulmonary fibrosis (IPF) is a progressive, often fatal interstitial lung disease characterized by a unique pattern of scarring, inflammation, fibroblast proliferation, and connective-tissue matrix protein deposition in the lungs. MN-001 (tipelukast), a novel, orally bioavailable small molecule, demonstrated anti-inflammatory and anti-fibrotic activity in preclinical models, blocks leukotriene receptors and inhibits both phosphodiesterase 4 and 5lipoxygenase. In a bleomycin-induced pulmonary fibrosis murine model MN-001 significantly reduced lung fibrosis and lung hydroxyproline content. The study aim is to evaluate the safety, tolerability and efficacy of MN-001 in IPF(NCT02503657). We describe the study design and participant characteristics of the first clinical trial evaluating MN-001 in individuals diagnosed with IPF.METHODS Study Design: A single-center, randomized (2:1), placebo-controlled, double-blind (D-B), 6-month study followed by a 6-month open-label extension (OLE) phase in patients with moderate to severe IPF. Inclusion criteria: physician diagnosed IPF (ATS Guidelines, 2011), males and females aged 21 to 80 years, GAP Stage II-III; on no anti-fibrotic or on stable dose nintedanib. Exclusion criteria: malignancy, listed for lung transplantation, on pirfenidone (due to anticipated drug interaction). Participants were given MN-001 750 mg or placebo PO bid for the 26-week D-B treatment. In the six-month OLE phase, all participants received MN001 750 mg PO bid. The primary endpoint is mean change in FVC from baseline to 26 weeks. Secondary endpoints include safety, tolerability, and other disease activity assessments as measured by 6-minute walk test (6MWT), Modified Medical Research Council Dyspnea Score (MMRC), and Quality of Life (ATAQ-IPF) at 26 weeks. Additional endpoints are frequency of worsening of IPF and time to first worsening of IPF, defined by the 6MWT and MMRC.RESULTS D-B Phase: This table summarizes enrollment characteristics. Last patient last visit was completed on December 7, 2020. All randomized participants completed 6 months D-B treatment.
OLE Phase: One participant terminated early during OLE phase due to disease progression. Overall, 14 participants completed 12 months of study drug treatment. Safety: All enrolled participants experienced at least one adverse event with the most frequently reported AEs occurring in the Gastrointestinal disorders SOC. During the study, three serious adverse events were reported and were judged to be unrelated to study drug. Following database lock, we will analyze the following endpoints: FVC, 6MWT, MMRC, and ATAQ-IPF.CONCLUSIONS We have successfully completed this single-center, placebo-controlled trial, to evaluate its efficacy, safety and tolerability of MN-001 as a therapy for IPF and are continuing analysis of study outcomes.
Author Block: R. Bascom1, K. Hitz1, A. E. Dimmock1, M. Makhay2, K. Matsuda2; 1MS Hershey Medical Ctr, Penn State Univ, Hershey, PA, United States, 2MediciNova, La Jolla, CA, United States.
BACKGROUND
Idiopathic pulmonary fibrosis (IPF) is a progressive, often fatal interstitial lung disease characterized by a unique pattern of scarring, inflammation, fibroblast proliferation, and connective-tissue matrix protein deposition in the lungs. MN-001 (tipelukast), a novel, orally bioavailable small molecule, demonstrated anti-inflammatory and anti-fibrotic activity in preclinical models, blocks leukotriene receptors and inhibits both phosphodiesterase 4 and 5lipoxygenase. In a bleomycin-induced pulmonary fibrosis murine model MN-001 significantly reduced lung fibrosis and lung hydroxyproline content. The study aim is to evaluate the safety, tolerability and efficacy of MN-001 in IPF(NCT02503657). We describe the study design and participant characteristics of the first clinical trial evaluating MN-001 in individuals diagnosed with IPF.METHODS Study Design: A single-center, randomized (2:1), placebo-controlled, double-blind (D-B), 6-month study followed by a 6-month open-label extension (OLE) phase in patients with moderate to severe IPF. Inclusion criteria: physician diagnosed IPF (ATS Guidelines, 2011), males and females aged 21 to 80 years, GAP Stage II-III; on no anti-fibrotic or on stable dose nintedanib. Exclusion criteria: malignancy, listed for lung transplantation, on pirfenidone (due to anticipated drug interaction). Participants were given MN-001 750 mg or placebo PO bid for the 26-week D-B treatment. In the six-month OLE phase, all participants received MN001 750 mg PO bid. The primary endpoint is mean change in FVC from baseline to 26 weeks. Secondary endpoints include safety, tolerability, and other disease activity assessments as measured by 6-minute walk test (6MWT), Modified Medical Research Council Dyspnea Score (MMRC), and Quality of Life (ATAQ-IPF) at 26 weeks. Additional endpoints are frequency of worsening of IPF and time to first worsening of IPF, defined by the 6MWT and MMRC.RESULTS D-B Phase: This table summarizes enrollment characteristics. Last patient last visit was completed on December 7, 2020. All randomized participants completed 6 months D-B treatment.
OLE Phase: One participant terminated early during OLE phase due to disease progression. Overall, 14 participants completed 12 months of study drug treatment. Safety: All enrolled participants experienced at least one adverse event with the most frequently reported AEs occurring in the Gastrointestinal disorders SOC. During the study, three serious adverse events were reported and were judged to be unrelated to study drug. Following database lock, we will analyze the following endpoints: FVC, 6MWT, MMRC, and ATAQ-IPF.CONCLUSIONS We have successfully completed this single-center, placebo-controlled trial, to evaluate its efficacy, safety and tolerability of MN-001 as a therapy for IPF and are continuing analysis of study outcomes.
