Clinical Study of ART-123 for the Treatment of Acute Exacerbation of Idiopathic Pulmonary Fibrosis

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

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.

Study Overview

• Status: Completed
• Conditions: Idiopathic Pulmonary Fibrosis
• Intervention / Treatment: Drug: ART-123; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 74
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Chiba, Japan
  • Fukuoka, Japan
  • Kumamoto, Japan
  • Nagasaki, Japan
  • Aichi
    • Nagoya, Aichi, Japan
    • Seto, Aichi, Japan
  • Chiba
    • Kamogawa, Chiba, Japan
    • Sakura, Chiba, Japan
  • Fukuoka
    • Kurume, Fukuoka, Japan
  • Gifu
    • Ogaki, Gifu, Japan
  • Hyogo
    • Himeji, Hyogo, Japan
    • Kobe, Hyogo, Japan
  • Ibaragi
    • Naka, Ibaragi, Japan
  • Kanagawa
    • Yokohama, Kanagawa, Japan
  • Miyagi
    • Sendai, Miyagi, Japan
  • Nara
    • Tenri, Nara, Japan
  • Okanaya
    • Kurashiki, Okanaya, Japan
  • Osaka
    • Osakasayama, Osaka, Japan
    • Sakai, Osaka, Japan
  • Shizuoka
    • Hamamatsu, Shizuoka, Japan
  • Tochigi
    • Shimotsuke, Tochigi, Japan
  • Tokyo
    • Bunkyo, Tokyo, Japan
    • Minato, Tokyo, Japan
    • Ota, Tokyo, Japan
    • Shibuya, Tokyo, Japan
    • Shinjuku, Tokyo, Japan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 85 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo	Drug: Placebo; Placebo by intravenous drip infusion in addition to standard of care steroid therapy
EXPERIMENTAL: ART-123	Drug: ART-123; 380 U/kg/day by intravenous drip infusion in addition to standard of care steroid therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Survival rate on Day 90	90 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall survival	180 days after the start of investigational product administration in the last subject
Survival time up to Day 90	90days
P/F ratio	4 days, 7 days, 15 days, 28 days, 60 days, 90 days
Coagulation tests	4 days, 7 days, 15days, 28 days, 60 days, 90 days

Other Outcome Measures

Outcome Measure	Time Frame
Chest imaging findings (chest HRCT findings)	Within 90days
Blood gas test	Within 90days
mMRC	Within 90days
CAT	Within 90days
Dyspnea-12	Within 90days
Duration of respiration management	Within 90days
Inflammatory markers	Within 90days
Interstitial pneumonia markers	Within 90days
Total duration of respiratory system-related inpatient hospitalization	Within 90days
Adverse events (AEs)	Within 90days
AEs related to hemorrhage	Within 90days
Routine laboratory tests	Within 90days
Vital signs	Within 90days
Presence of anti-drug antibodies	Within 90days

Collaborators and Investigators

• Sponsor: Asahi Kasei Pharma Corporation

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: May 1, 2016
• Primary Completion (ACTUAL): September 1, 2018
• Study Completion (ACTUAL): December 1, 2018

Study Registration Dates

• First Submitted: April 1, 2016
• First Submitted That Met QC Criteria: April 11, 2016
• First Posted (ESTIMATE): April 15, 2016

Study Record Updates

• Last Update Posted (ACTUAL): January 18, 2019
• Last Update Submitted That Met QC Criteria: January 17, 2019
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Keywords: Idiopathic pulmonary fibrosis; Acute exacerbations; Recombinant human soluble thrombomodulin; ART-123
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Fibrosis; Pulmonary Fibrosis; Idiopathic Pulmonary Fibrosis
• Other Study ID Numbers: ART-123-AEIPF-301