A Phase II Study to Evaluate the Efficacy and Safety of SYH2059 Tablets in Adult Patients With Idiopathic Pulmonary Fibrosis

Official title

A Multicenter, Randomized, Double-blind, Placebo-controlled Phase II Study to Evaluate the Efficacy and Safety of SYH2059 Tablets in Adult Patients With Idiopathic Pulmonary Fibrosis.

Overview

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

• Drug SYH2059 Tablets
  Take twice daily, about 12 hours apart, after meals, for 12 weeks.
• Drug Placebo
  Take twice daily, about 12 hours apart, after meals, for 12 weeks.

Primary outcome measures

• Change in FVC from baseline (mL) [Time frame: Week 12]

Secondary outcome measures (12)

• Change in FVC from baseline (mL) [Time frame: Week 2,4,8]
• Change in FVCpp from baseline [Time frame: Week 12]
• Proportion of participants with an absolute decrease in FVCpp >10% from baseline [Time frame: Week 12]
• Proportion of participants with no decrease in FVCpp from baseline [Time frame: Week 12]
• Adjusted change in DLCOpp from baseline [Time frame: Week 12]
• Change from baseline in L-PF scale score [Time frame: Week 12]
• Changes in IPF symptoms (cough, dyspnea, fatigue) assessed by VAS from baseline [Time frame: Week 12]
• Incidence and severity of adverse events [Time frame: Week 13]
• Changes in C-SSRS over time during the trial [Time frame: Week 13]
• Plasma concentrations of sparsely sampled participants pre-dose and 2 hours post-dose on Day 14 and Day 84 [Time frame: Week 2,12]
• PK parameters after the first dose in intensively sampled participants: Cmax. [Time frame: Day 1]
• PK parameters after the first dose in intensively sampled participants: AUC0-12. [Time frame: Day 1]

Eligibility criteria

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 Exclusion Criteria (for PK intensive sampling participants):
• 23\. Previous history of gastrointestinal surgery that may interfere with the PK of the investigational product.
• 24\. Alcohol consumption exceeding 14 units per week within 4 weeks prior to screening.
• 25\. Habitual excessive intake of xanthine- or caffeine-containing foods, beverages, or other substances affecting drug absorption, distribution, metabolism or excretion within 4 weeks prior to screening.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07600021 · SYH2059-003

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗