Clinical trial NCT02739165: Clinical Study of ART-123 for the Treatment of Acute Exacerbation of Idiopathic Pulmonary Fibrosis
Official title: Phase III Clinical Study of ART-123 for the Treatment of Acute Exacerbation of Idiopathic Pulmonary Fibrosis: a Multicenter Randomized Placebo-controlled Double-blind Study to Assess the Efficacy and Safety of ART-123
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Idiopathic Pulmonary Fibrosis
Keywords: Acute exacerbations
Idiopathic pulmonary fibrosis
Recombinant human soluble thrombomodulin
ART-123
Lead sponsor: Asahi Kasei Pharma Corporation
Sponsor class: INDUSTRY
First posted: 2016-04-15
Enrollment: 74
Sex: ALL
Minimum age (years): 40
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to assess the efficacy and safety of the intravenous drip infusion of ART-123 in patients with acute exacerbation of idiopathic pulmonary fibrosis (IPF) in a multicenter, double-blind, randomized, placebo-controlled, parallel group comparison study, and to confirm its superiority over placebo with survival rate on Day 90 as the primary endpoint.


Eligibility criteria: Main Inclusion Criteria:

* Patients diagnosed with IPF who meet all criteria from (1) through (4) during the course of IPF
* (1)Unexplained development or worsening of dyspnea within 1 month during the course of IPF
* (2)Finding of new, bilateral ground glass opacities and/or consolidation on HRCT
* (3)No apparent Pulmonary infections, pneumothorax, malignant tumors, pulmonary embolism, or left heart failure
* (4)A decrease\* in PaO2 of ≥10 mmHg or SpO2 of ≥4% under the same conditions compared with the level at the previous measurements

  * (\*) In cases where no PaO2 or SpO2 test values under the same conditions are available, a patient with a P/F ratio ≤300 in the current episode of acute exacerbation is considered to have met criterion (4)
* Aged 40 years or older and no older than 85 years at the time of informed consent with either sex

Main Exclusion Criteria:

* Have intracranial hemorrhage, pulmonary hemorrhage, gastrointestinal bleeding (continued hematemesis, bloody discharge, gastrointestinal ulcer-induced hemorrhage)
* Have a history of cerebrovascular disorder (e.g., cerebral hemorrhage or cerebral infarction) within 52 weeks (364 days) before informed consent
* Patients for whom the completion of hemostatic treatment has not been confirmed after undergoing surgery of the central nervous system or after trauma
* Have a high risk for fatal or life-threatening hemorrhage
* Patients with malignant tumors
* Have acute exacerbation attributable to drug induced pulmonary disorder, after surgery for malignant tumors, chemotherapy, or radiation therapy
* Have acute exacerbation due to a thoracic surgical procedure (including thoracoscopic lung biopsy)
* Have a history of acute exacerbation of IPF
* Receiving mechanical ventilation through intratracheal intubation
* Patients who are pregnant or nursing, or who may be pregnant
* Patients with a platelet count less than 100,000/uL at the time of enrollment
* Patients with severe renal (serum Cr: ≥4 mg/dL) or hepatic (AST/ALT: ≥500 IU/L or T-Bil: ≥10 mg/dL) dysfunction
* Have been administered a commercially available thrombomodulin alfa (recombinant )(Recomodulin® for Intravenous Injection 12800) within 30 days before the start of investigational product administration
* Have a history of hypersensitivity for investigational product

Primary outcomes:
measure: Survival rate on Day 90
timeFrame: 90 days
Secondary outcomes:
measure: Overall survival
timeFrame: 180 days after the start of investigational product administration in the last subject
measure: Survival time up to Day 90
timeFrame: 90days
measure: P/F ratio
timeFrame: 4 days, 7 days, 15 days, 28 days, 60 days, 90 days
measure: Coagulation tests
timeFrame: 4 days, 7 days, 15days, 28 days, 60 days, 90 days
Other outcomes:
measure: Chest imaging findings (chest HRCT findings)
timeFrame: Within 90days
measure: Blood gas test
timeFrame: Within 90days
measure: mMRC
timeFrame: Within 90days
measure: CAT
timeFrame: Within 90days
measure: Dyspnea-12
timeFrame: Within 90days
measure: Duration of respiration management
timeFrame: Within 90days
measure: Inflammatory markers
timeFrame: Within 90days
measure: Interstitial pneumonia markers
timeFrame: Within 90days
measure: Total duration of respiratory system-related inpatient hospitalization
timeFrame: Within 90days
measure: Adverse events (AEs)
timeFrame: Within 90days
measure: AEs related to hemorrhage
timeFrame: Within 90days
measure: Routine laboratory tests
timeFrame: Within 90days
measure: Vital signs
timeFrame: Within 90days
measure: Presence of anti-drug antibodies
timeFrame: Within 90days
Locations:
city: Nagoya
country: Japan
state: Aichi
city: Seto
country: Japan
state: Aichi
city: Kamogawa
country: Japan
state: Chiba
city: Sakura
country: Japan
state: Chiba
city: Kurume
country: Japan
state: Fukuoka
city: Ogaki
country: Japan
state: Gifu
city: Himeji
country: Japan
state: Hyogo
city: Kobe
country: Japan
state: Hyogo
city: Naka
country: Japan
state: Ibaragi
city: Yokohama
country: Japan
state: Kanagawa
city: Sendai
country: Japan
state: Miyagi
city: Tenri
country: Japan
state: Nara
city: Kurashiki
country: Japan
state: Okanaya
city: Osakasayama
country: Japan
state: Osaka
city: Sakai
country: Japan
state: Osaka
city: Hamamatsu
country: Japan
state: Shizuoka
city: Shimotsuke
country: Japan
state: Tochigi
city: Bunkyo
country: Japan
state: Tokyo
city: Minato
country: Japan
state: Tokyo
city: Ota
country: Japan
state: Tokyo
city: Shibuya
country: Japan
state: Tokyo
city: Shinjuku
country: Japan
state: Tokyo
city: Chiba
country: Japan
city: Fukuoka
country: Japan
city: Kumamoto
country: Japan
city: Nagasaki
country: Japan
Study officials:
affiliation: Asahi Kasei Pharma Corporation
name: Asahi Kasei Pharma Corporation
role: STUDY_CHAIR
References:
citation: Kondoh Y, Azuma A, Inoue Y, Ogura T, Sakamoto S, Tsushima K, Johkoh T, Fujimoto K, Ichikado K, Matsuzawa Y, Saito T, Kishi K, Tomii K, Sakamoto N, Aoshima M, Araya J, Izumi S, Arita M, Abe M, Yamauchi H, Shindoh J, Suda T, Okamoto M, Ebina M, Yamada Y, Tohda Y, Kawamura T, Taguchi Y, Ishii H, Hashimoto N, Abe S, Taniguchi H, Tagawa J, Bessho K, Yamamori N, Homma S. Thrombomodulin Alfa for Acute Exacerbation of Idiopathic Pulmonary Fibrosis. A Randomized, Double-Blind Placebo-controlled Trial. Am J Respir Crit Care Med. 2020 May 1;201(9):1110-1119. doi: 10.1164/rccm.201909-1818OC.