Idiopathic Pulmonary Fibrosis
Conditions
Brief summary
This is a multicenter, randomized, double-blind, placebo-controlled Phase II study. It Aims aims to evaluate the efficacy and safety of different doses of SYH2059 tablets compared with placebo in adult patients with IPF, observe the PK profile of SYH2059 tablets in adult IPF patients, and assess the population pharmacokinetic (PPK) profile, exposure-response (E-R) relationship, as well as the changing trends of blood biomarkers.
Interventions
DRUGSYH2059 Tablets
Take twice daily, about 12 hours apart, after meals, for 12 weeks.
DRUGPlacebo
Take twice daily, about 12 hours apart, after meals, for 12 weeks.
Sponsors
InnovStone Therapeutics Limited
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Eligible participants will be randomly assigned to one of the treatment groups in a 1:1:1:1 ratio.
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 1\. Age ≥ 40 years, regardless of gender; * 2\. The investigator confirms the clinical diagnosis of IPF in participants based on chest HRCT, surgical lung biopsy, or transbronchial lung cryobiopsy (if available) performed during the screening period or within 1 year prior to screening (see Appendix 13.7 for details); * 3\. FVCpp ≥ 45% during the screening period; * 4\. Hemoglobin-corrected DLCOpp ≥ 25% and \< 90% during the screening period; * 5\. Received a single stable-dose antifibrotic therapy for at least 12 weeks prior to screening (concurrent use of nintedanib and pirfenidone is prohibited) and will continue after randomization; or had not received stable antifibrotic therapy, or had discontinued such therapy for at least 8 weeks, with no plan to initiate antifibrotic therapy during the trial; * 6\. Understands the purpose and risks of this study, comprehends and agrees to comply with all study procedures, consents to participate, and provides written informed consent.
Exclusion criteria
* 1\. Interstitial lung disease other than IPF. * 2\. Airway obstruction during screening (FEV₁/FVC \< 0.7), or emphysema greater than pulmonary fibrosis on HRCT. * 3\. Confirmed or suspected acute exacerbation of IPF within 3 months prior to screening. * 4\. Investigator judgment that IPF severity showed sustained improvement during the 12 months prior to screening, based on changes in FVC, DLCO and/or HRCT findings. * 5\. Other clinically significant respiratory diseases during screening. * 6\. Severe diseases in any other system (cardiovascular, digestive, neurological, hematological, endocrine) during screening. * 7\. Malignancy within 5 years prior to screening (excluding treated basal cell carcinoma of the skin, in situ squamous cell carcinoma of the skin, or carcinoma in situ of the cervix). * 8\. Any acute infection within 2 weeks prior to screening that has not fully recovered per investigator judgment. * 9\. Active, unstable or uncontrolled vasculitis within 8 weeks prior to screening. * 10\. Any acute or chronic active infection during screening. * 11\. C-SSRS assessment during screening indicating suicidal behavior within the past 2 years (actual attempt, interrupted attempt, aborted attempt, or preparatory acts or gestures), or clinically significant suicidal ideation within 3 months prior to screening or during screening (participant answered "yes" to C-SSRS suicidal ideation question 4 or 5). * 12\. Treatment with PDE1, PDE3, PDE4, PDE10 inhibitors, or non-selective PDE inhibitors within 4 weeks prior to screening. * 13\. Use of strong CYP3A4 inhibitors or inducers within 14 days or 5 half-lives (whichever is longer) before the first dose of investigational product, or inability to discontinue such agents during the study. * 14\. Receiving immunomodulatory agents (excluding oral glucocorticoids) for respiratory or pulmonary conditions during screening, or prednisone (or equivalent) at a daily dose \> 15 mg. * 15\. Abnormal hepatic and renal function during screening: ALT, AST \> 2.5 × ULN, or TBIL \> 1.5 × ULN, or eGFR \< 30 mL/min/1.73 m². * 16\. Severe, persistent, uncontrolled hypertension during screening (SBP ≥ 180 mmHg or DBP ≥ 100 mmHg). * 17\. History of smoking within 3 months prior to screening or unwillingness to abstain from smoking (including e-cigarettes) during the study. * 18\. Hypersensitivity to SYH2059 or any excipients, or history of severe drug allergy. * 19\. Participation in any clinical trial within 4 weeks prior to screening (excluding those not receiving investigational product). * 20\. Participation in a clinical study of the same target drug and receipt of treatment within 3 months prior to screening. * 21\. Pregnant or lactating females; fertile females or males unwilling to practice strict contraception throughout the trial and for 3 months after trial completion until the end of the safety follow-up period (including male participants). Any other conditions deemed inappropriate for trial participation by the investigator. * 22\. Additional
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in FVC from baseline (mL) | Week 12 | FVC is one of the pulmonary function indicators; FVC values in patients with IPF tend to decrease. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in FVC from baseline (mL) | Week 2,4,8 | FVC is one of the pulmonary function indicators; FVC values in patients with IPF tend to decrease. |
| Change in FVCpp from baseline | Week 12 | — |
| Proportion of participants with an absolute decrease in FVCpp >10% from baseline | Week 12 | — |
| Proportion of participants with no decrease in FVCpp from baseline | Week 12 | — |
| Adjusted change in DLCOpp from baseline | Week 12 | — |
| Change from baseline in L-PF scale score | Week 12 | The L-PF questionnaire is used to assess patients' symptoms. It consists of 21 items covering two main domains: the Symptom Module and the Impact Module. Higher scores indicate more severe symptoms and poorer quality of life. |
| Changes in IPF symptoms (cough, dyspnea, fatigue) assessed by VAS from baseline | Week 12 | The Visual Analogue Scale (VAS) is a commonly used clinical tool for assessing the intensity of subjective symptoms. It typically consists of a 0 - 10 cm line segment, where 0 indicates no symptoms and 10 indicates the most severe symptoms. |
| Incidence and severity of adverse events | Week 13 | — |
| Changes in C-SSRS over time during the trial | Week 13 | The Columbia Suicide Severity Rating Scale (C-SSRS) is an internationally recognized standardized tool for suicide risk assessment. It systematically evaluates suicidal ideation , suicidal behavior and self-injurious behavior. Suicidal ideation is graded in severity on a 1 -5 scale, with higher scores indicating stronger suicidal ideation. |
| Plasma concentrations of sparsely sampled participants pre-dose and 2 hours post-dose on Day 14 and Day 84 | Week 2,12 | — |
| PK parameters after the first dose in intensively sampled participants: Cmax. | Day 1 | — |
| PK parameters after the first dose in intensively sampled participants: AUC0-12. | Day 1 | — |
| PK parameters after the first dose in intensively sampled participants: Tmax. | Day 1 | — |
| PK parameters after multiple doses in intensively sampled participants: Ctau,ss. | Week 1,2 | — |
| PK parameters after multiple doses in intensively sampled participants: Cmax,ss | Week 1,2 | — |
| PK parameters after multiple doses in intensively sampled participants: Cmin,ss. | Week 1,2 | — |
| PK parameters after multiple doses in intensively sampled participants: AUC0-tau,ss. | Week 1,2 | — |
| PK parameters after multiple doses in intensively sampled participants: Tmax,ss. | Week 1,2 | — |
| Changes in blood biomarkers from baseline. | Week 4,8,12 | — |
Contacts
CONTACTClinical Trials Information Group officer
Outcome results
None listed