A Study of PMG1015 Injection in Idiopathic Pulmonary Fibrosis Subjects

IPF Clinical Trial

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05895565
• Other study ID #: PMG1015_CHN_Ib
• Status: Recruiting
• Phase: Phase 1
• Start date: May 19, 2023
• Est. completion date: May 27, 2025

Study information

• Verified date: April 2023
• Source: Pulmongene Ltd.
• Contact: Yaohui Wang, BA
• Phone: 86-010-69776688
• Email: yaohui_wang[@]pulmongene.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: May 27, 2025
• Est. primary completion date: December 20, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 85 Years

Eligibility

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.

Related Conditions & MeSH terms

• Idiopathic Pulmonary Fibrosis
• IPF
• Pulmonary Fibrosis

Intervention

Drug:
• PMG1015
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.
• PMG1015 placebo
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.

Locations

Country	Name	City	State
China	China-Japan Friendship Hospital	Beijing	Beijing
China	The First Affiliated Hospital of Guangzhou Medical University	Guangzhou	Guangdong
China	The Second Hospital of Anhui Medical University	Hefei	Anhui
China	Nanjing Drum Tower Hospital	Nanjing	Jiangsu
China	Shanghai Chest Hospital	Shanghai	Shanghai
China	Shanghai Pulmonary Hospital	Shanghai	Shanghai
China	Tongji Hospital, Tongji Medical College of HUST	Wuhan	Hubei

Sponsors (1)

Lead Sponsor	Collaborator
Pulmongene Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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	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.
Secondary	Evaluate the PK parameter of the area under the concentration-time curve from time zero to infinity (AUC0-8) 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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	Evaluate the PK parameter of the elimination rate constant (?z) of PMG1015.	?z 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.
Secondary	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.
Secondary	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.