Phase ll Study of HEC585 in Patients With IPF

Study Overview
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Brief Summary
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A Phase ll Study to evaluate the efficacy and safety of various doses of HEC585 Tablets in patients with idiopathic pulmonary fibrosis

Official Title
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A Phase II, Multi-center, Randomized, Placebo-controlled (Double-blind Design), Active Comparator-controlled (Open-label Design), Parallel-group, Dose-finding Study, to Evaluate the Efficacy and Safety of HEC585 Tablets in Patients With IPF

Conditions
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Idiopathic Pulmonary Fibrosis

Intervention / Treatment
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* Drug: HEC585
* Drug: Pirfenidone
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Volunteer to participate in this clinical study and sign the ICF before the study begins; Aged 40-80 (including 40 and 80) ; Female or male subjects with child-bearing potential who agree and promise to take effective contraceptive measures; Diagnosed with IPF according to the Official ATS/ERS/JRS/ALAT Clinical Practice Guideline for IPF Diagnosis (2018); FEV1/FVC ≥ 0.7; FVC ≥ 45% predicted; DLCO corrected for Haemoglobin (Hb) ≥ 30% predicted of normal; In the opinion of the Investigator, subjects are willing and able to comply with the protocol requirements and attend the visit. Exclusion Criteria: In the opinion of the Investigator, subjects underwent significant deterioration in IPF within one month before randomization; Interstitial lung disease caused by other known causes; Any bacterial, viral, parasitic or fungal infection that needs to be treated at screening; Expected to receive lung transplantation during the study; Expected survival is less than 6 months; History of tumors within 5 years before screening (except for localized cancers such as basal cell carcinoma); Moderate to severe hepatic insufficiency (Child-Pugh grade B or C, see Appendix 4); History of unstable or worsening heart disease within 6 months before screening; Cannot perform 6MWT or PFT; Allergic to any component of HEC585 Tablets or pirfenidone tablets; Participated in other clinical study and received the last dose within 3 months before screening; Pregnant or breastfeeding; History of smoking within 3 months before screening or are unwilling to quit smoking during the study; Subjects often drink alcohol within 6 months before the screening (drink more than 21 units of alcohol a week), or refuse to reduce alcohol intake during the study; History of drug abuse within 6 months before the screening; Family or personal history of QT prolongation syndrome; 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. TBil > 1.5 × ULN or AST or ALT > 2 × ULN; CLcr < 50 mL/min; Human immunodeficiency virus (HIV) antibody is positive; Uncontrolled hepatitis B virus infection or hepatitis C virus infection; QTcF > 480 ms. Subjects have received any of the following treatments within 28 days before randomization: Any cytotoxic drug or immunosuppressant Therapeutic drugs for IPF, including but not limited to pirfenidone, nintedanib, prednisone at > 15 mg/d or other glucocorticoids of the equivalent dose, N-acetylcysteine at > 600 mg/d. Moderate and strong inhibitor or strong inducer of CYP1A2. Strong inducers or strong CYP3A4 inhibitors.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HEC585 dose A<br>Drug: HEC585 dose A once daily, up to 24 weeks-120 weeks | Drug: HEC585<br>* HEC585 Tablets，once daily<br>|
| Experimental: HEC585 dose B<br>Drug: HEC585 dose B once daily, up to 24 weeks-120 weeks | Drug: HEC585<br>* HEC585 Tablets，once daily<br>|
| Experimental: HEC585 dose C<br>Drug: HEC585 dose C once daily, up to 24 weeks-120 weeks | Drug: HEC585<br>* HEC585 Tablets，once daily<br>|
| Active Comparator: pirfenidone<br>Drug: pirfenidone three times a day (target dose), up to 24 weeks | Drug: Pirfenidone<br>* Pirfenidone，three times a day<br>|
| Placebo Comparator: placebo<br>Drug: placebo once daily, up to 24 weeks-120 weeks | Drug: Placebo<br>* Placebo，once daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline to Week 24 in %FVC compared with placebo | change in %FVC, measured using Spirometer, from baseline to week 24 | 24 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline to Week 24 in %FVC compared with Pirfenidone | change in %FVC, measured using Spirometer, from baseline to week 24 | 24 Weeks | 
| Change from Baseline to Week 12 in %FVC compared with placebo/ Pirfenidone | change in %FVC, measured using Spirometer, from baseline to week 12 | 12 Weeks | 
| Proportion of subjects with an absolute decline from baseline in FVC (% predicted) of > 10% | The proportion of subjects whose %FVC decline from baseline by more than 10% in each treatment group at W24 | 24 Weeks | 
| Time to first acute IPF exacerbation |  | 24 Weeks | 
| All-cause mortality |  | 24 Weeks | 
| IPF related mortality |  | 24 Weeks | 
| Changes of 6MWT results |  | 12 Weeks, 24 Weeks | 
| Changes of SGRQ scores |  | 12 Weeks, 24 Weeks | 
| Changes of DLco (Hb correction) |  | 12 Weeks, 24 Weeks | 
| Changes of resting SpO2 |  | 12 Weeks, 24 Weeks |