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The main goal of this phase llb study is to compare the efficacy and safety of two doses of HEC585 tablets with placebo which is a look-alike substance that contains no active drug in patients with progressive fibrosing interstitial lung diseases. This study is divided into two stages, i.e. main study stage with 24 weeks treatment duration followed by up to 96 weeks treatment extended study stage.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| HEC585 tables does A | Experimental |
| |
| HEC585 tables does B | Experimental |
| |
| placebo | Placebo Comparator | Placebo once daily up to 24 weeks in main stage; HEC585 dose A once daily up to 96 weeks in extended stage |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| HEC585 dose A | Drug | taking HEC585 dose A orally once daily, up to 24 weeks in main stage (if applicable); up to 96 weeks in extended stage |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change from Baseline to Week 24 in FVC (mL) compared with placebo | change in FVC (mL), measured using Spirometer, from baseline to week 24 | 24 Weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Change from Baseline to Week 12 in FVC (mL) compared with placebo | change in FVC (mL), measured using Spirometer, from baseline to week 12 | 12 Weeks |
| Proportion of subjects with the decline from baseline in FVC (% predicted) > 10% |
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Inclusion Criteria:
Volunteer to participate and sign the ICF.
Male or female patients' age ≥ 18 years when signing the ICF.
Patients with known or unknown etiology (except IPF) and clear pulmonary fibrosis on chest CT have undergone conventional clinical treatment (assessed by the investigator, including follow-up observation) for ≥ 3 months. At least two of the following criteria occurring within 12 months before screening without alternative explanation (such as infection, heart failure, etc.):
i) Worsening respiratory symptoms like cough, shortness of breath. ii) Physiological evidence of disease progression (either of the following):
Fibrosing lung disease on HRCT, defined as reticular abnormality with traction bronchiectasis with or without honeycombing, with disease extent of >10% as confirmed by central readers.
For patients with underlying connective tissue disease (CTD) should be in the stable status which is defined by no initiation of new therapy, treatment dose adjustment or withdrawal of therapy within 12 weeks prior to randomization.
FEV1/FVC ≥ 0.7 before using bronchodilators.
%FVC ≥ 45% predicted.
Carbon Monoxide Diffusion Capacity (DLCO) corrected for Haemoglobin (Hb) ≥ 30% and ≤ 80% predicted of normal.
Fertile female or male subjects agreed and promised to take effective contraception measures from signing the ICF till 30 days after last administration.
Subjects are willing and able to comply with the protocol requirements and attend visits assessed by the investigator.
Exclusion Criteria:
Diagnosis of Idiopathic Pulmonary Fibrosis (IPF).
Lung with other clinically significant abnormalities which the investigator assess to have an effect on the results of study.
Significant Pulmonary Arterial Hypertension (PAH), such as meeting the following: Previous clinical or echocardiographic evidence of significant right heart failure, History of right heart catheterization showing a cardiac index ≤ 2 L/min/m², or PAH requiring parenteral therapy with epoprostenol/treprostinil.
Major extrapulmonary physiological or pathological restriction (e.g. chest wall abnormality, large pleural effusion).
Expected to receive lung transplantation during the study.
Expected survival time is less than 6 months.
History of malignant tumors within 5 years (except for localized cancers such as basal cell carcinoma and carcinoma in situ of cervix).
Thyroid dysfunction that the investigator assessed to be clinically significant and needed to be treated.
History of unstable or worsening heart disease during the 6 months prior to screening, including but not limited to the following:
TBIL >1.2 × ULN, AST or ALT > 1.5 × ULN.
CLcr < 50 mL/min.
Human immunodeficiency virus (HIV) or treponema pallidum antibody is positive.
Uncontrolled hepatitis B virus infection or hepatitis C virus infection.
Use of any of the following medications for the treatment of Interstitial Lung Disease (ILD) or influence the effect or safety of investigational drug:
Subjects cannot complete the PFT、6MWT,or questionnaires.
Allergic to any component of HEC585 Tablets.
Participated in other clinical study and received the last dose within 3 months before screening.
Pregnant or breastfeeding.
History of smoking (≥ 10 cigarettes/day) within 3 months before screening or are unwilling to quit smoking during the study.
History of alcohol or drug abuse within 6 months before the screening.
Any condition that, in the opinion of the investigator, would compromise the safety or compliance of the subject, or prevent the subject from completing the study.
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| HuaPing Dai, Ph.D | Contact | 010-84206271 | daihuaping@ccmu.edu.cn |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| China-Japan Friendship Hospital | Recruiting | Beijing | Beijing Municipality | China |
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| HEC585 dose B | Drug | taking HEC585 dose B orally once daily, up to 24 weeks in main stage; up to 96 weeks in extended stage |
|
| Placebo | Drug | taking Placebo orally once daily, up to 24 weeks in main stage |
|
The proportion of subjects whose %FVC decline from baseline by more than 10% in each treatment group at week 24
| 24 Weeks |
| Proportion of subjects with the decline from baseline in FVC (% predicted) > 5% | The proportion of subjects whose %FVC decline from baseline by more than 5% in each treatment group at week 24 | 24 Weeks |
| Changes of DLco (Hb correction) | 12 Weeks, 24 Weeks |
| Changes of 6MWT results | 12 Weeks, 24 Weeks |
| Changes of St George' s Respiratory Questionnaire (SGRQ) | The higher the score, the more serious the impact on life | 12 Weeks, 24 Weeks |
| Changes of The University of California San Diego Shortness of Breath Questionnaire (UCSD SOBQ) | Scores range from 0 to 120. The higher the score, the more severe the difficulty in breathing | 12 Weeks, 24 Weeks |
| Changes of Leicester coughing questionnaire scores | Scores range from 3 to 21. The lower the score, the greater the impact of cough on quality of life | 12 Weeks, 24 Weeks |
| Changes of HRCT | 24 Weeks |
| Time to first acute ILD exacerbation or death | the time duration from randomization to first acute ILD exacerbation or death whichever occurs first | 24 Weeks |
| Proportion of subjects with death caused by any reason(s) | 24 Weeks |
| Proportion of subjects with death caused by the respiratory reason | 24 Weeks |