A Study of PMG1015 Injection in Idiopathic Pulmonary Fibrosis Subjects

Study Overview
=================
Brief Summary
-----------------
Idiopathic Pulmonary Fibrosis (IPF): It is a progressive and fatal fibrosing interstitial lung disease of unknown etiology, with a median survival of only 2 to 3 years. Epidemiology of IPF (with reference to the international epidemiological studies due to the lack of accurate epidemiological data in China): the incidence was 2 to 30 per 100,000 person years, and the prevalence was 10 to 60 per 100,000. More males suffer from IPF than females. In population aged more than 65 years, the estimated prevalence was up to 400 per 100,000. Medications for IPF: Currently there is no medication with definitely significant efficacy (such as slowing down the disease progression). However, the following drugs can be used as appropriate based on the results of randomized and controlled clinical trials conducted in recent years and taking account of the patients' actual clinical conditions. Pirfenidone: It has been proven to remarkably slow down forced vital capacity (FVC) decline and reduce the risk of death to a certain degree, with the side effects of photosensitivity, asthenia, rash, stomach upset, and anorexia. Pirfenidone is recommended for IPF patients accompanying with mild to moderate pulmonary dysfunction in clinical practice. Nintedanib: It could remarkably slow down the absolute value of FVC decline in IPF patients, thereby slowing down the disease progression to a certain degree. The most common adverse reaction of Nintedanib is diarrhoea. Future therapeutic strategies for IPF: A multi-drug concomitant therapy against different therapeutic targets for pulmonary fibrosis may be a potential strategy, among which, the research and development of anti-fibrotic drugs may be most valuable in treatment of this disease, with promising potentials of halting or reversing disease progression, extending the life expectancy, improving the quality of life, and reducing the side effects.

Official Title
-----------------
A Phase Ib, Multi-center, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of PMG1015 Injection After Multiple Ascending Doses in Subjects With Idiopathic Pulmonary Fibrosis (IPF)

Conditions
-----------------
IPF

Intervention / Treatment
-----------------
* Drug: PMG1015
* Drug: PMG1015 placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 1. Able to understand the study procedures and method, willing to complete the study as required by the clinical study protocol, and sign the ICF; 2. Males or females, aged between 40 and 85 years of age, inclusive at signature of ICF. 3. Body weight ≥ 50 kg for males and ≥40 kg for females; 4. Diagnosis of IPF (HRCT diagnosis of UIP pattern/probable UIP pattern [as reviewed and confirmed by experts from independent imaging review team] with or without a pathologic diagnosis of UIP pattern/probable UIP pattern; if HRCT diagnosis is indeterminate for UIP, then a pathologic diagnosis of UIP pattern/probable UIP pattern is required) as defined by current American Thoracic Society (ATS)/European Respiratory Society (ERS)/Japanese Respiratory Society (JRS)/Latin American Thoracic Association (ALAT) Clinical Practice Guidelines for IPF (2022) (Pathological examination refers to transbronchial lung cryobiopsy or surgical/pleuroscopic lung biopsy); 5. Forced vital capacity percent predicted (FVCpp) ≥45% at screening; 6. Diffusing capacity of the lung for carbon monoxide (DLCO; corrected for haemoglobin) from 30% to 90% of the predicted, inclusive at screening; 7. Patients not receiving any approved IPF treatment (Pirfenidone or Nintedanib) for any reasons within 1 month before randomization, including those who were not tolerant or responsive to prior treatment with approved drugs (Pirfenidone or Nintedanib), or those who disagree to receive the approved IPF treatment after discussion with the investigator on the risks or benefits of such medications (Note: It's not allowed for any subject to discontinue the approved IPF treatment for inclusion into this study). Exclusion Criteria: 1. Patients with instable condition of IPF as assessed by the investigator at screening, and those with acute exacerbation of IPF during screening or within 3 months prior to randomization; 2. Patients who are likely to be lung transplant recipients within 6 months or expected to survive less than 1 year as assessed by the investigator at screening; 3. Patients with range of emphysema more than that of pulmonary fibrosis as indicated by chest HRCT (conclusion from independent imaging review shall prevail) at screening; 4. Patients accompanying with obstructive airway diseases (such as FEV1/FVC < 0.7 after bronchodilator therapy); 5. Patients accompanying with an interstitial lung disease other than IPF; 6. Patients accompanying with other types of respiratory disorders, which may affect the study results as assessed by the investigator; 7. Patients who require ≥ 15 hours of daily oxygen therapy; 8. Oxygen saturation at rest in room air measured by a finger pulse oximeter <90% (0-1500 meters above the sea level) or <85% (>1500 meters above the sea level) at screening; 9. Patients who received corticosteroids (Prednisone Acetate Tablets > 15 mg/day or an equivalent dose of other corticosteroids) within 1 month prior to screening; 10. Patients who received any cytotoxic drug, immunosuppressant, cytokine regulator, or receptor antagonist (including but not limited to Methotrexate, Azathioprine, Mycophenolate Mofetil, Cyclophosphamide, Cyclosporin) within 4 weeks prior to screening; 11. Patients who received vasodilator therapy for pulmonary arterial hypertension (e.g. Bosentan) within 1 month prior to screening; 12. Patients accompanying with other uncontrolled underlying diseases (congestive heart failure, acute myocardial infarction, unstable angina pectoris, hemorrhagic stroke, or ischemic stroke categorized as New York Heart Association [NYHA] Class III, or IV, as well as pulmonary arterial hypertension requiring intervention within 6 months prior to screening), for which the patient is not considered suitable for the study as assessed by the investigator; 13. Patients who had active tuberculosis within 12 months prior to screening, or clinical symptoms of bacterial, viral, fungal or microbial infections requiring intervention within 4 weeks prior to randomization; 14. Patients with coronavirus disease-2019 (COVID-19) diagnosis within 1 month prior to screening and/or at screening (COVID-19 nucleic acid test is not a required procedure of the study, but may be performed if necessary); 15. Patients who were vaccinated or plan to get vaccinated against COVID-19 and other diseases within 1 month prior to screening and up to 1 month after the last dose; 16. Patients with history of malignancies (excluding recovered basal cell carcinoma and cervical carcinoma in situ) within 5 years prior to screening, or under evaluation of any potential malignancies; 17. Alanine Aminotransferase (ALT) or Aspartate Aminotransferase (AST) ≥ 2×Upper Limit of Normal (ULN) or Total Bilirubin ≥1.5×ULN; 18. Serum creatinine ≥1.5×ULN; 19. Patients with active hepatitis, syphilis, or positive for HIV antibody; 20. Patients who had a major surgery (under general anesthesia) within 3 months prior to screening, or plan to undergo a surgery during the study, which may affect the evaluation of the study endpoints as assessed by the investigator; 21. Patients who participated in any clinical trials (of, including, other investigational drugs/devices) within 3 months prior to screening, or within 5 half-lives at screening; 22. A former smoker who quitted for ≤ 3 months, or unable to quit smoking throughout the study; 23. A suspected or confirmed alcohol or drug abuser; 24. Patients who have known allergic reaction to the investigational product or its APIs, or history of allergic reaction to human, humanized, chimeric, or murine monoclonal antibodies or any substances contained in the excipients; 25. Pregnant or lactating women; female subjects who plan to become pregnant during the study, or patients who are not willing to take contraceptive measures as required by the protocol during the study; 26. Other conditions that preclude the patient from participating in the study as assessed by the investigator.

Ages Eligible for Study
-----------------
Minimum Age: 40 Years
Maximum Age: 85 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: At screening, each subject will be identified by a screening number, and each screened subject shall have a unique screening number. Each subject will be assigned with a screening number after signing the informed consent form (ICF). Eligible subjects will be randomized and enter the administration and observation period to receive the study drug (PMG1015 or placebo), and will be assigned with a corresponding subject ID and a drug number. The randomization scheme will be generated using the Rava RTSM system.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental<br>Including 3 dose groups (15 mg/kg, 30 mg/kg and 40 mg/kg), with 10 subjects (8 of whom receiving the investigational product) enrolled into each group. Intravenous infusion for 30 min (±5 min), once every 4 weeks, for 3 doses. | Drug: PMG1015<br>* Strength: 100 mg/2 mL/vial. Dosage and Administration: Intravenous infusion of PMG1015 at 15 mg/kg, 30 mg/kg and 40 mg/kg for 30 min (±5 min), once every 4 weeks, for 3 doses.<br>|
| Placebo Comparator: Placebo Comparator<br>Including 3 dose groups (15 mg/kg, 30 mg/kg and 40 mg/kg), with 10 subjects (2 of whom receiving placebo) enrolled into each group. Intravenous infusion for 30 min (±5 min), once every 4 weeks, for 3 doses. | Drug: PMG1015 placebo<br>* The placebo injection of PMG1015 contains the same excipients as PMG1015 Injection, only without the active substance. Strength: 2 mL/vial. Dosage and Administration: A single dose of placebo. Intravenous infusion for 30 min (±5 min), once every 4 weeks, for 3 doses.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and severity of Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) occurring during the study | Based on the currently available non-clinical data and disclosed clinical data, the adverse events that may occur during the study include: Infusion-related hypersensitivity reaction; Headache; Symptoms of the digestive system: Nausea, diarrhoea; Elevated liver enzymes: Alanine aminotransferase (ALT) increased, Aspartate aminotransferase (AST) increased, and Gamma-glutamyl transpeptidase increased; Abnormal blood lipids: Blood triglycerides increased; Other unexpected adverse reactions. Criteria for Serious Adverse Events (SAEs): Results in death Is life-threatening Requires or prolongs hospitalization Causes persistent or significant disability or incapacity Results in congenital anomalies or birth defects Death due to disease progression Important medical event | Throughout the study，approximately 2 years. | 
| Assessment of vital sign measurement results-respiratory rate | Vital signs will be measured at screening and each follow-up visit, to access the changes from baseline to post-dose in respiratory rate (breaths/min). | Throughout the study，approximately 2 years. | 
| Assessment of vital sign measurement results-pulse rate | Vital signs will be measured at screening and each follow-up visit, to access the changes from baseline to post-dose in pulse rate (beats/min). | Throughout the study，approximately 2 years. | 
| Assessment of vital sign measurement results-body temperature | Vital signs will be measured at screening and each follow-up visit, to access the changes from baseline to post-dose in body temperature (℃). | Throughout the study，approximately 2 years. | 
| Assessment of vital sign measurement results-sitting blood pressure | Vital signs will be measured at screening and each follow-up visit, to access the changes from baseline to post-dose in sitting blood pressure (mmHg). | Throughout the study，approximately 2 years. | 
| Title: Title: Assessment of Physical Examination results - skin | Physical Examination will be measured at screening and each follow-up visit, to access the changes from baseline to post-dose in skin (normal, abnormal). | Throughout the study，approximately 2 years. | 
| Title: Assessment of Physical Examination results - head | Physical Examination will be measured at screening and each follow-up visit, to access the changes from baseline to post-dose in head (normal, abnormal). | Throughout the study，approximately 2 years. | 
| Title: Assessment of Physical Examination results - neck | Physical Examination will be measured at screening and each follow-up visit, to access the changes from baseline to post-dose in neck (normal, abnormal). | Throughout the study，approximately 2 years. | 
| Assessment of Physical Examination results - oral cavity | Physical Examination will be measured at screening and each follow-up visit, to access the changes from baseline to post-dose in oral cavity (normal, abnormal). | Throughout the study，approximately 2 years. | 
| Assessment of Physical Examination results - chest | Physical Examination will be measured at screening and each follow-up visit, to access the changes from baseline to post-dose in chest (normal, abnormal). | Throughout the study，approximately 2 years. | 
| Assessment of Physical Examination results - abdomen | Physical Examination will be measured at screening and each follow-up visit, to access the changes from baseline to post-dose in abdomen (normal, abnormal). | Throughout the study，approximately 2 years. | 
| Assessment of Physical Examination results - lymph nodes | Physical Examination will be measured at screening and each follow-up visit, to access the changes from baseline to post-dose in lymph nodes (normal, abnormal). | Throughout the study，approximately 2 years. | 
| Assessment of Physical Examination results - neurological | Physical Examination will be measured at screening and each follow-up visit, to access the changes from baseline to post-dose in neurological (normal, abnormal). | Throughout the study，approximately 2 years. | 
| Assessment of Physical Examination results - psychiatric status | Physical Examination will be measured at screening and each follow-up visit, to access the changes from baseline to post-dose in psychiatric status (normal, abnormal). | Throughout the study，approximately 2 years. | 
| Assessment of Physical Examination results - extremities | Physical Examination will be measured at screening and each follow-up visit, to access the changes from baseline to post-dose in extremities (normal, abnormal). | Throughout the study，approximately 2 years. | 
| Assessment of Physical Examination results - weight | Physical examination will be performed at screening and each dose, to assess the changes from baseline to post-dose in weight (kilograms). | Throughout the study，approximately 2 years. | 
| Assessment of Physical Examination results - height | Physical examination will be performed at screening and each dose, to assess the changes from baseline to post-dose in height (meters). | Throughout the study，approximately 2 years. | 
| Assessment of 12-lead electrocardiogram (ECG) results - heart rate | Three ECG scans should be taken at the same time point, with no more than 2 minutes between scans.12-lead electrocardiogram (ECG) will be measured at screening and each follow-up visit, to access the changes from baseline to post-dose in heart rate (beats per minute). | Throughout the study，approximately 2 years. | 
| Assessment of 12-lead electrocardiogram (ECG) results - RR interval | Three ECG scans should be taken at the same time point, with no more than 2 minutes between scans.12-lead electrocardiogram (ECG) will be measured at screening and each follow-up visit, to access the changes from baseline to post-dose in RR interval (milliseconds). | Throughout the study，approximately 2 years. | 
| Assessment of 12-lead electrocardiogram (ECG) results - PR interval | Three ECG scans should be taken at the same time point, with no more than 2 minutes between scans.12-lead electrocardiogram (ECG) will be measured at screening and each follow-up visit, to access the changes from baseline to post-dose in PR interval (milliseconds). | Throughout the study，approximately 2 years. | 
| Assessment of 12-lead electrocardiogram (ECG) results - QRS complex | Three ECG scans should be taken at the same time point, with no more than 2 minutes between scans.12-lead electrocardiogram (ECG) will be measured at screening and each follow-up visit, to access the changes from baseline to post-dose in QRS complex (milliseconds). | Throughout the study，approximately 2 years. | 
| Assessment of 12-lead electrocardiogram (ECG) results - QTc interval | Three ECG scans should be taken at the same time point, with no more than 2 minutes between scans.12-lead electrocardiogram (ECG) will be measured at screening and each follow-up visit, to access the changes from baseline to post-dose in QTc interval (milliseconds). | Throughout the study，approximately 2 years. | 
| Assessment of Hematology results - blood cell counts | Hematology will be measured at screening and each follow-up visit, to access the changes from baseline to post-dose in blood cell counts (cells/μL). | Throughout the study，approximately 2 years. | 
| Assessment of Hematology results - white blood cell differential counts | Hematology will be measured at screening and each follow-up visit, to access the changes from baseline to post-dose in white blood cell differential counts (including eosinophil count and percentage, basophil count and percentage, neutrophil count and percentage, lymphocyte and monocyte count and percentage). | Throughout the study，approximately 2 years. | 
| Assessment of Hematology results - red blood cell count | Hematology will be measured at screening and each follow-up visit, to access the changes from baseline to post-dose in red blood cell count (cells/μL). | Throughout the study，approximately 2 years. | 
| Assessment of Hematology results - hematocrit | Hematology will be measured at screening and each follow-up visit, to access the changes from baseline to post-dose in hematocrit (%). | Throughout the study，approximately 2 years. | 
| Assessment of Hematology results - hemoglobin content | Hematology will be measured at screening and each follow-up visit, to access the changes from baseline to post-dose in hemoglobin content (g/dL). | Throughout the study，approximately 2 years. | 
| Assessment of Hematology results - platelet count | Hematology will be measured at screening and each follow-up visit, to access the changes from baseline to post-dose in platelet count (cells/μL). | Throughout the study，approximately 2 years. | 
| Assessment of Urinalysis results - pH | Urinalysis will be measured at screening and each follow-up visit, to access the changes from baseline to post-dose in pH. | Throughout the study，approximately 2 years. | 
| Assessment of Urinalysis results - specific gravity | Urinalysis will be measured at screening and each follow-up visit, to access the changes from baseline to post-dose in specific gravity. | Throughout the study，approximately 2 years. | 
| Assessment of Urinalysis results - protein | Urinalysis will be measured at screening and each follow-up visit, to access the changes from baseline to post-dose in protein (negative/+/++/+++). | Throughout the study，approximately 2 years. | 
| Assessment of Urinalysis results - glucose | Urinalysis will be measured at screening and each follow-up visit, to access the changes from baseline to post-dose in glucose (negative/+/++/+++). | Throughout the study，approximately 2 years. | 
| Assessment of Urinalysis results - ketones | Urinalysis will be measured at screening and each follow-up visit, to access the changes from baseline to post-dose in ketones (negative/+/++/+++). | Throughout the study，approximately 2 years. | 
| Assessment of Urinalysis results - red blood cells | Urinalysis will be measured at screening and each follow-up visit, to access the changes from baseline to post-dose in red blood cells (cells/HP). | Throughout the study，approximately 2 years. | 
| Assessment of Urinalysis results - white blood cells | Urinalysis will be measured at screening and each follow-up visit, to access the changes from baseline to post-dose in white blood cells (cells/HP). | Throughout the study，approximately 2 years. | 
| Assessment of Blood biochemistry results - blood glucose | Blood biochemistry will be measured at screening and each follow-up visit, to access the changes from baseline to post-dose in blood glucose (mmol/L). | Throughout the study，approximately 2 years. | 
| Assessment of Blood biochemistry results - triglycerides | Blood biochemistry will be measured at screening and each follow-up visit, to access the changes from baseline to post-dose in triglycerides (mmol/L). | Throughout the study，approximately 2 years. | 
| Assessment of Blood biochemistry results - total cholesterol | Blood biochemistry will be measured at screening and each follow-up visit, to access the changes from baseline to post-dose in total cholesterol (mmol/L). | Throughout the study，approximately 2 years. | 
| Assessment of Blood biochemistry results - direct bilirubin | Blood biochemistry will be measured at screening and each follow-up visit, to access the changes from baseline to post-dose in direct bilirubin (μmol/L). | Throughout the study，approximately 2 years. | 
| Assessment of Blood biochemistry results - alanine aminotransferase | Blood biochemistry will be measured at screening and each follow-up visit, to access the changes from baseline to post-dose in alanine aminotransferase (ALT,U/L). | Throughout the study，approximately 2 years. | 
| Assessment of Blood biochemistry results - albumin quantification | Blood biochemistry will be measured at screening and each follow-up visit, to access the changes from baseline to post-dose in albumin quantification (g/dL). | Throughout the study，approximately 2 years. | 
| Assessment of Blood biochemistry results - total bilirubin | Blood biochemistry will be measured at screening and each follow-up visit, to access the changes from baseline to post-dose in total bilirubin (μmol/L). | Throughout the study，approximately 2 years. | 
| Assessment of Blood biochemistry results - creatinine | Blood biochemistry will be measured at screening and each follow-up visit, to access the changes from baseline to post-dose in creatinine (μmol/L). | Throughout the study，approximately 2 years. | 
| Assessment of Blood biochemistry results - urea/urea nitrogen | Blood biochemistry will be measured at screening and each follow-up visit, to access the changes from baseline to post-dose in urea/urea nitrogen (mmol/L). | Throughout the study，approximately 2 years. | 
| Assessment of Blood biochemistry results - uric acid | Blood biochemistry will be measured at screening and each follow-up visit, to access the changes from baseline to post-dose in uric acid (μmol/L). | Throughout the study，approximately 2 years. | 
| Assessment of Blood biochemistry results - potassium | Blood biochemistry will be measured at screening and each follow-up visit, to access the changes from baseline to post-dose in potassium (mmol/L). | Throughout the study，approximately 2 years. | 
| Assessment of Blood biochemistry results - sodium | Blood biochemistry will be measured at screening and each follow-up visit, to access the changes from baseline to post-dose in sodium (mmol/L). | Throughout the study，approximately 2 years. | 
| Assessment of Blood biochemistry results - chloride | Blood biochemistry will be measured at screening and each follow-up visit, to access the changes from baseline to post-dose in chloride (mmol/L). | Throughout the study，approximately 2 years. | 
| Assessment of Blood biochemistry results - total calcium | Blood biochemistry will be measured at screening and each follow-up visit, to access the changes from baseline to post-dose in total calcium (mmol/L). | Throughout the study，approximately 2 years. | 
| Assessment of Blood biochemistry results - inorganic phosphorus | Blood biochemistry will be measured at screening and each follow-up visit, to access the changes from baseline to post-dose in inorganic phosphorus (mmol/L). | Throughout the study，approximately 2 years. | 
| Assessment of Blood biochemistry results - creatine kinase | Blood biochemistry will be measured at screening and each follow-up visit, to access the changes from baseline to post-dose in creatine kinase (CK,U/L). | Throughout the study，approximately 2 years. | 
| Assessment of Blood biochemistry results - creatine kinase-MB | Blood biochemistry will be measured at screening and each follow-up visit, to access the changes from baseline to post-dose in creatine kinase-MB (CK-MB,ng/mL). | Throughout the study，approximately 2 years. | 
| Assessment of Blood biochemistry results - troponin I | Blood biochemistry will be measured at screening and each follow-up visit, to access the changes from baseline to post-dose in troponin I (TnI,ng/mL). | Throughout the study，approximately 2 years. | 
| Assessment of Blood biochemistry results - myoglobin | Blood biochemistry will be measured at screening and each follow-up visit, to access the changes from baseline to post-dose in myoglobin (ng/mL). | Throughout the study，approximately 2 years. | 
| Assessment of Coagulation results- prothrombin time | Coagulation will be measured at screening and each follow-up visit, to access the changes from baseline to post-dose in prothrombin time (PT, seconds). | Throughout the study，approximately 2 years. | 
| Assessment of Coagulation results- activated partial thromboplastin time | Coagulation will be measured at screening and each follow-up visit, to access the changes from baseline to post-dose in activated partial thromboplastin time (APTT, seconds). | Throughout the study，approximately 2 years. | 
| Assessment of Coagulation results- international normalized ratio | Coagulation will be measured at screening and each follow-up visit, to access the changes from baseline to post-dose in international normalized ratio (INR). | Throughout the study，approximately 2 years. | 
| Assessment of Coagulation results- fibrinogen | Coagulation will be measured at screening and each follow-up visit, to access the changes from baseline to post-dose in fibrinogen (mg/dL). | Throughout the study，approximately 2 years. | 
| Assessment of pulmonary function test results-forced vital capacity (FVC) | Pulmonary function test is a test to explore the functional status of human respiratory system with the knowledge of exercise respiratory physiology and modern examination technology. The changes from baseline to post-dose in forced vital capacity (FVC) (L) will be assessed at baseline and the second dose, and after the last dose. | Throughout the study，approximately 2 years. | 
| Assessment of pulmonary function test results-forced vital capacity percent predicted (FVCpp) | Pulmonary function test is a test to explore the functional status of human respiratory system with the knowledge of exercise respiratory physiology and modern examination technology. The changes from baseline to post-dose in forced vital capacity percent predicted (FVCpp) (%) will be assessed at baseline and the second dose, and after the last dose. | Throughout the study，approximately 2 years. | 
| Assessment of pulmonary function test results-forced expiratory volume in 1 second (FEV1) | Pulmonary function test is a test to explore the functional status of human respiratory system with the knowledge of exercise respiratory physiology and modern examination technology. The changes from baseline to post-dose in forced expiratory volume in 1 second (FEV1) (L) will be assessed at baseline and the second dose, and after the last dose. | Throughout the study，approximately 2 years. | 
| Assessment of pulmonary function test results-diffusing capacity of the lungs for carbon monoxide (DLCO) | Pulmonary function test is a test to explore the functional status of human respiratory system with the knowledge of exercise respiratory physiology and modern examination technology. The changes from baseline to post-dose in diffusing capacity of the lungs for carbon monoxide (DLCO) (mL/min/mmHg) will be assessed at baseline and the second dose, and after the last dose. | Throughout the study，approximately 2 years. | 
| Assessment of pulmonary function test results-diffusing capacity of the lungs for carbon monoxide percent predicted (DLCOpp) | Pulmonary function test is a test to explore the functional status of human respiratory system with the knowledge of exercise respiratory physiology and modern examination technology. The changes from baseline to post-dose in diffusing capacity of the lungs for carbon monoxide percent predicted (DLCOpp) (DLCO%) will be assessed at baseline and the second dose, and after the last dose. | Throughout the study，approximately 2 years. | 
| Evaluate chest high-resolution computed tomography (HRCT) results. | Chest HRCT is a type of CT used for diagnosing diseases of the chest. The HRCT diagnosis should include UIP-type/maybe UIP-type (confirmed by an independent imaging review group expert) with or without pathological UIP-type/maybe UIP-type; non-definitive UIP diagnosed by HRCT requires pathological UIP-type/maybe UIP-type (pathology refers to cryopreserved lung biopsy or surgical/thoracoscopic lung biopsy). Chest HRCT will be performed at screening and each dose, and after the last dose, to assess the changes from baseline to post-dose in Chest HRCT. | Throughout the study，approximately 2 years. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate the pharmacokinetic (PK) parameter of the area under the concentration-time curve from time zero to the last quantifiable time point (AUC0-t) of PMG1015. | AUC is a pharmacokinetic parameter that represents the concentration of a drug in the blood at a certain time. | Throughout the study，approximately 2 years. | 
| Evaluate the PK parameter of the area under the concentration-time curve from time zero to infinity (AUC0-∞) of PMG1015. | AUC is a pharmacokinetic parameter that represents the concentration of a drug in the blood at a certain time. | Throughout the study，approximately 2 years. | 
| Evaluate the PK parameter of the area under the concentration-time curve from time zero to the dosing interval (AUC0-tau) of PMG1015. | AUC is a pharmacokinetic parameter that represents the concentration of a drug in the blood at a certain time. | Throughout the study，approximately 2 years. | 
| Evaluate the PK parameter of the maximum concentration (Cmax) of PMG1015. | Cmax refers to the highest concentration of a drug in the blood after administration, which is related to the dose, route of administration, dosing frequency, and time to reach the peak concentration. | Throughout the study，approximately 2 years. | 
| Evaluate the PK parameter of the time to reach the maximum concentration (Tmax) of PMG1015. | Tmax refers to the time when a drug reaches its maximum concentration and exhibits its maximum effect in the body. | Throughout the study，approximately 2 years. | 
| Evaluate the PK parameter of the elimination half-life (t1/2) of PMG1015. | t1/2 refers to the time required for the drug concentration in the blood to decrease by half. | Throughout the study，approximately 2 years. | 
| Evaluate the PK parameter of the clearance rate (CL) of PMG1015. | CL is the volume of liquid containing a drug that is completely eliminated by the excretory organs per unit time, and its unit is usually mL·(min·kg)-1 or L·(h·kg)-1. | Throughout the study，approximately 2 years. | 
| Evaluate the PK parameter of the distribution volume (Vz) of PMG1015. | Vz is a pharmacokinetic parameter that reflects the extent of drug distribution in various tissues in the body. | Throughout the study，approximately 2 years. | 
| Evaluate the PK parameter of the elimination rate constant (λz) of PMG1015. | λz refers to the ratio of the amount of compound eliminated per unit time to the total amount, with its unit being the reciprocal of time. | Throughout the study，approximately 2 years. | 
| Relationship between the dose and exposure. | Dose refers to the quantity of drug administered at one time that produces a therapeutic effect. | Throughout the study，approximately 2 years. | 
| Incidence of PMG1015-induced and PMG1015-enhanced ADAs. | Immunogenicity assessment is mainly based on anti-drug antibodies (ADAs), including the incidence of PMG1015-induced and PMG1015-enhanced ADAs. | Throughout the study，approximately 2 years. |