Idiopathic Pulmonary Fibrosis (IPF)
Conditions
Brief summary
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.
Detailed description
\[Stage 1 study design\] Stage 1 is divided into a screening period, a main study treatment period, an extension treatment period, and a safety visit period. Based on a previous Phase 2 study, it is planned to enrol 80 subjects. All subjects who may participate in this study will enter the screening period (no more than 4 weeks) after voluntarily signing the informed consent form, and the investigator will assess the eligibility of the subjects according to the inclusion and exclusion criteria. All subjects will be re-assessed for eligibility before randomisation, and those who meet the criteria can enter the main study treatment period. \[Stage 2 study design\] Stage 2 is divided into a screening period, a main study treatment period, an extension treatment period, and a safety visit period. It is initially planned to enrol 428 subjects, and the target population for both stages is the same. The inclusion and exclusion criteria and randomisation procedure for the screening period of Stage 2 are the same as those for Stage 1. The main study treatment period is 52 weeks. The dosing regimen and dose adjustment plan for the investigational medicinal product in Stage 2 are the same as those in Stage 1. The proportion of subjects receiving IPF therapeutic drugs shall not be less than 40% of the total number of subjects.
Interventions
DRUGTDI01
TDI01 suspension
Sponsors
Beijing Tide Pharmaceutical Co., Ltd
China-Japan Friendship Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Double-blind
Intervention model description
TDI01 400 mg group and the placebo group at a 1:1 ratio
Eligibility
Sex/Gender
ALL
Age
40 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Diagnosed with IPF 1. 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); 2. 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; 2. Voluntarily participates in this clinical study and signs the informed consent form before the start of the study; 3. Age is 40-80 years (inclusive of 40 and 80 years) at the time of signing the informed consent form, regardless of sex; 4. 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; 5. Stable disease for at least 8 weeks prior to Visit 1. Patients must meet one of the following two criteria: 1. 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); 2. 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 \[\*stable treatment is defined as the patient being able to generally tolerate continuous treatment with an unchanged dose of pirfenidone (400 mg TID and above) or nintedanib (100 mg BID and above)\]; 6. At screening and baseline, forced expiratory volume in one second (FEV1)/FVC ratio ≥ 0.70; 7. At screening and baseline, FVC% of predicted is greater than 50% (inclusive); 8. DLco (Hb-corrected) percent of predicted normal value is greater than 30% (inclusive) at screening and at baseline; 9. 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; 10. In the investigator's assessment, the subject is willing and able to comply with protocol requirements and attend visits.
Exclusion criteria
Inclusion criteria Subjects who meet each of the following criteria will be allowed to participate in this study: 1. Diagnosed with IPF 1. 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); 2. 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; 2. Voluntarily participates in this clinical study and signs the informed consent form before the start of the study; 3. Age is 40-80 years (inclusive of 40 and 80 years) at the time of signing the informed consent form, regardless of sex; 4. 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; 5. Stable disease for at least 8 weeks prior to Visit 1. Patients must meet one of the following two criteria: 1. 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); 2. 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 \[\*stable treatment is defined as the patient being able to generally tolerate continuous treatment with an unchanged dose of pirfenidone (400 mg TID and above) or nintedanib (100 mg BID and above)\]; 6. At screening and baseline, forced expiratory volume in one second (FEV1)/FVC ratio ≥ 0.70; 7. At screening and baseline, FVC% of predicted is greater than 50% (inclusive); 8. DLco (Hb-corrected) percent of predicted normal value is greater than 30% (inclusive) at screening and at baseline; 9. 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; 10. In the investigator's assessment, the subject is willing and able to comply with protocol requirements and attend visits.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Primary Outcome Measure | Week 24, Week 52. | Absolute change in forced vital capacity (FVC) (mL) from baseline at Week 24 and week 52. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Secondary efficacy endpoints: | Week 6 ,Week 12 | Absolute change in FVC (mL) from baseline at Weeks 6 and 12. |
| Secondary Outcome Measure | Week 24, Week 52 | Time (days) to the first occurrence of ppFVC% absolute decline \>10%, acute exacerbation of IPF (AE-IPF), hospitalisation due to respiratory causes, or death due to respiratory causes (whichever occurs first) during the trial period; |
| Safety endpoints: | week 24, week 52 | Adverse event assessment and other safety indicator evaluations (including high-resolution CT, laboratory tests, 12-lead ECG, vital signs, physical examination, etc.). |
Countries
China
Contacts
CONTACTHuaPing Dai, Dr.
Outcome results
None listed