A Multicentre, Randomised, Double-blind, Placebo-controlled, Adaptive Design Clinical Trial to Evaluate the Efficacy and Safety of TDI01 Suspension in the Treatment of Idiopathic Pulmonary Fibrosis (IPF)
This study is a multicentre, randomised, double-blind, placebo-controlled, adaptive design clinical trial to evaluate the efficacy and safety of TDI01 suspension in the treatment of idiopathic pulmonary fibrosis (IPF). The study will be conducted in China and divided into two stages, both of which are multicentre, randomised, double-blind, placebo-controlled studies. Stage 1 aims to evaluate the efficacy and safety of TDI01 suspension compared to the placebo group in the treatment of IPF patients, and Stage 2 aims to further confirm the efficacy and safety of TDI01 suspension compared to the placebo group in the treatment of IPF patients.
• Diagnosed with IPF
∙ Confirmed diagnosis before screening: Diagnosis was made according to the 2022 clinical practice guideline principles of the American Thoracic Society (ATS), European Respiratory Society (ERS), Japanese Respiratory Society (JRS), and Latin American Thoracic Society (ALAT) (see Appendix 1), confirmed by the investigators based on chest high-resolution CT (HRCT) performed within 12 months before Visit 1, and surgical lung biopsy or transbronchial lung cryobiopsy (if available);
‣ Reconfirmation of IPF diagnosis at screening: And before Visit 2, the independent imaging review panel of experts reviewed and confirmed that the HRCT (HRCT within 3 months before randomisation in the same site was accepted) is consistent with a clinical diagnosis of usual interstitial pneumonia (UIP) or probable UIP for IPF. For subjects with an HRCT finding of indeterminate for UIP, if a local (previous) surgical lung biopsy or transbronchial lung cryobiopsy has been performed, the pathological slides must be submitted for central review and assessment. If the histopathological features show UIP or probable UIP, the clinical diagnosis of IPF can be confirmed;
• Voluntarily participates in this clinical study and signs the informed consent form before the start of the study;
• Age is 40-80 years (inclusive of 40 and 80 years) at the time of signing the informed consent form, regardless of sex;
• Female or male subjects of childbearing potential agree and commit to using highly effective contraceptive measures (see Appendix 8 in 19.8) from the time of signing the informed consent form until 90 days after the last dose of the investigational medicinal product;
• Stable disease for at least 8 weeks prior to Visit 1. Patients must meet one of the following two criteria:
∙ Did not receive treatment with nintedanib and/or pirfenidone for at least 8 weeks prior to Visit 1 (including patients not treated with nintedanib/pirfenidone and those who had failed treatment with nintedanib/pirfenidone);
‣ Or have been receiving a stable\* regimen of nintedanib or pirfenidone for at least 12 weeks prior to Visit 1, and plan to continue receiving this background therapy stably after randomisation \[\*stable treatment is defined as the patient being able to generally tolerate continuous treatment with an unchanged dose of pirfenidone (400 mg TID and above) or nintedanib (100 mg BID and above)\];
• At screening and baseline, forced expiratory volume in one second (FEV1)/FVC ratio ≥ 0.70;
• At screening and baseline, FVC% of predicted is greater than 50% (inclusive);
• DLco (Hb-corrected) percent of predicted normal value is greater than 30% (inclusive) at screening and at baseline;
• Active bacterial, viral, parasitic, or fungal infection requiring systemic treatment within 4 weeks prior to screening, but the infection is judged by the investigator to be cured during the screening period;
⁃ In the investigator's assessment, the subject is willing and able to comply with protocol requirements and attend visits.
• Subjects who meet each of the following criteria will be allowed to participate in this study:
• Diagnosed with IPF
∙ Confirmed diagnosis before screening: Diagnosis was made according to the 2022 clinical practice guideline principles of the American Thoracic Society (ATS), European Respiratory Society (ERS), Japanese Respiratory Society (JRS), and Latin American Thoracic Society (ALAT) (see Appendix 1), confirmed by the investigators based on chest high-resolution CT (HRCT) performed within 12 months before Visit 1, and surgical lung biopsy or transbronchial lung cryobiopsy (if available);
‣ Reconfirmation of IPF diagnosis at screening: And before Visit 2, the independent imaging review panel of experts reviewed and confirmed that the HRCT (HRCT within 3 months before randomisation in the same site was accepted) is consistent with a clinical diagnosis of usual interstitial pneumonia (UIP) or probable UIP for IPF. For subjects with an HRCT finding of indeterminate for UIP, if a local (previous) surgical lung biopsy or transbronchial lung cryobiopsy has been performed, the pathological slides must be submitted for central review and assessment. If the histopathological features show UIP or probable UIP, the clinical diagnosis of IPF can be confirmed;
• Voluntarily participates in this clinical study and signs the informed consent form before the start of the study;
• Age is 40-80 years (inclusive of 40 and 80 years) at the time of signing the informed consent form, regardless of sex;
• Female or male subjects of childbearing potential agree and commit to using highly effective contraceptive measures (see Appendix 8 in 19.8) from the time of signing the informed consent form until 90 days after the last dose of the investigational medicinal product;
• Stable disease for at least 8 weeks prior to Visit 1. Patients must meet one of the following two criteria:
∙ Did not receive treatment with nintedanib and/or pirfenidone for at least 8 weeks prior to Visit 1 (including patients not treated with nintedanib/pirfenidone and those who had failed treatment with nintedanib/pirfenidone);
‣ Or have been receiving a stable\* regimen of nintedanib or pirfenidone for at least 12 weeks prior to Visit 1, and plan to continue receiving this background therapy stably after randomisation \[\*stable treatment is defined as the patient being able to generally tolerate continuous treatment with an unchanged dose of pirfenidone (400 mg TID and above) or nintedanib (100 mg BID and above)\];
• At screening and baseline, forced expiratory volume in one second (FEV1)/FVC ratio ≥ 0.70;
• At screening and baseline, FVC% of predicted is greater than 50% (inclusive);
• DLco (Hb-corrected) percent of predicted normal value is greater than 30% (inclusive) at screening and at baseline;
• Active bacterial, viral, parasitic, or fungal infection requiring systemic treatment within 4 weeks prior to screening, but the infection is judged by the investigator to be cured during the screening period;
⁃ In the investigator's assessment, the subject is willing and able to comply with protocol requirements and attend visits.