Radiation-Induced Pulmonary Fibrosis
Conditions
Interventions
TDI01 suspension 200 mg group:TDI01 suspension 200 mg once daily orally
TDI01 suspension 400 mg group:TDI01 suspension 400 mg once daily orally
Sponsors
West China Hospital, Sichuan University
Eligibility
Sex/Gender
All
Age
20 Years to 80 Years
Inclusion criteria
Inclusion criteria: Subjects who meet each of the following criteria will be allowed to participate in the study: 1. Diagnosing RIPF: 1.1 Diagnosed as chronic Radiation-Induced Pulmonary Fibrosis (RIPF) (1) The stage of the disease was consistent with the stage of chronic radiation-induced pulmonary fibrosis In this study, only patients with chronic radiation-induced pulmonary fibrosis (RIPF) were included, which was strictly defined as follows: 1) Patients had a definite history of thoracic radiotherapy (including but not limited to lung cancer, esophageal cancer, breast cancer, etc.), and the completion of radiotherapy was more than 6 months; 2) not in the stage of acute radiation pneumonitis (a stage characterized by inflammation within 1-6 months after radiotherapy); 3) did not receive or had no plans to receive radiotherapy during the study to exclude the effect of radiotherapy on the primary endpoint. (2) The clinical, imaging and exclusive diagnosis were consistent with the accepted diagnostic principles of RIPF Subjects must meet the following conditions: 1) Patients developed clinical manifestations consistent with radiation-induced pulmonary fibrosis within months to years after radiotherapy, including but not limited to progressive dyspnea, dry cough, decreased exercise tolerance, or chest tightness; 2) High resolution computed tomography (HRCT) of the chest completed within 12 months before the screening visit was preliminarly determined by the investigators, and the imaging findings were consistent with the characteristics of radiation-induced pulmonary fibrosis, including but not limited to: characteristic reticular opacification, honeycombing, traction bronchiectasis, and structural destruction of lung parenchyma with predominant radiation field distribution; 3) Other diseases that can cause similar imaging or clinical manifestations have been systematically excluded, including infectious pneumonia, drug-induced lung injury, connective tissue disease-related interstitial lung disease, idiopathic pulmonary fibrosis and other non-radiation-related interstitial lung diseases. (3) The severity grade was consistent with the study setting In this study, CTCAE v5.0 was used to classify the severity of radiation-induced lung injury: CTCAE grade 2-3 was included (4) independent image review and multidisciplinary confirmation To improve diagnostic consistency and accuracy, all prospective subjects must meet the following validation process: 1) Before the baseline visit, the HRCT (performed within 3 months before randomization in the same center) was reviewed by an independent imaging review panel to confirm that the HRCT was consistent with RIPF imaging characteristics; 2) If necessary, multidisciplinary discussion (MDT) was conducted with the respiratory, oncology, and radiotherapy departments. Comprehensive radiotherapy history, clinical manifestations, and imaging results were considered to confirm that the internationally recognized diagnostic principles of radiation-induced pulmonary fibrosis were met. 2. Voluntarily participate in the clinical study and sign the informed consent before the study begins; 3. At the time of signing the informed consent, the patients were 20-80 years old (including 20 and 80 years old), regardless of gender; 4. The female or male subject of potential fertility agrees and commits to use a highly effective contraceptive method from the date of signing the informed consent to 90 days after the last dose of the investig
Exclusion criteria
Exclusion criteria: Subjects who meet any of the following criteria will not be allowed to participate in the study: 1. Other known causes of interstitial lung disease, such as family or occupational environmental exposure, connective tissue disease, drugs, etc. 2. Have had active tuberculosis infection within 12 months before screening or any active bacterial, viral, parasitic, or fungal infection requiring systemic treatment 4 weeks before and during screening; 3. Unstable RIPF status as assessed by the investigator at screening, or acute exacerbation of RIPF within 8 weeks before and/or during screening; 4. Patients who are expected to receive organ transplantation (lung, liver, kidney, etc.) during the study or whose expected survival time is less than 8 months; 5. Use of any of the following treatments within 4 weeks before randomization: a) RIPF medications, nintedanib or pirfenidone for unstable treatment, prednisone > 15 mg/ day or other glucocorticoids at the same dose, and immunomodulators other than glucocorticoids for respiratory/pulmonary reasons; [Stable treatment was defined as patients who could tolerate pirfenidone (400mg TID or more) or nintedanib (100mg BID or more) for at least 8 weeks]. b) strong inhibitors of CYP3A4 (including but not limited to ritonavir, clarithromycin, idelalib, etc.); c) narrow therapeutic window substrates of CYP2C9 (e.g. warfarin, tolbutamide and phenytoin) and sensitive substrates of P-gp (e.g. digoxin); d) ROCK2 inhibitor (belumosudil); 6. Chemotherapy drugs that cause pulmonary fibrosis and targeted drugs such as bleomycin are being used or expected to be included in the treatment. 7. Laboratory test results at screening and baseline exceed any of the following criteria: total bilirubin > 2×ULN or AST/ALT > 5×ULN, serum CK > 1.5×ULN; 8. A history of unstable or worsening cardiac disease within 6 months before screening, including but not limited to the following: a) unstable angina pectoris; b) myocardial infarction; c) congestive heart failure requiring hospitalization or NYHA class III/IV; 9. Family history of long QT syndrome or sudden death, or significant electrocardiographic abnormalities at screening and baseline, including but not limited to: QTcF interval > 470 ms (women) or >450 ms (men), atrial fibrillation or flutter, second or third degree atrioventricular block, or left bundle branch block; 10. Systolic blood pressure > 160 mmHg or diastolic blood pressure >100 mmHg at screening and baseline (required after at least 5 minutes of rest and confirmed by one repeat); 11. Occurrence of cerebrovascular events leading to hospitalization within 12 months before screening, including but not limited to cerebral hemorrhage, subarachnoid hemorrhage, stroke, etc.; 12. Creatinine clearance (CLcr) at screening and baseline was < 50 mL/min, calculated by Cockcroft-Gault formula: [140- age (years)][weight (kg)]×(0.85, if female) / [72 x serum creatinine (mg/dL)]; 13. Inability to complete the 6-minute walk test (6MWD) or pulmonary function test (PFT); 14. Smoking history within 3 months before screening or unwillingness to quit smoking during the study; 15. History of drug abuse within 6 months before screening; 16. Pregnant or breastfeeding; 17. Nonnegative human immunodeficiency virus (HIV) antibody test at screening; 18. Allergic to any component of TDI01 suspension; 19. The last dose received in other clinical studies occurred within 3 months or 5 half-lives before screening, whichever was longer; 20. Major
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Forced Vital Capacity (FVC,mL);Lung ventilation/perfusion (V/Q) scan;Safety; | — |
Secondary
| Measure | Time frame |
|---|---|
| Percent predicted forced vital capacity (FVC%);Diffusing capacity of the lung for carbon monoxide (DLco);Pharmacokinetic (PK) ; | — |
Countries
China
Contacts
Public ContactYang Biao
West China Hospital, Sichuan University
Outcome results
None listed