A Phase Ⅰb/Ⅱa Clinical Study of IMC-003 Injection for the Treatment of Pulmonary Arterial Hypertension Receiving Background Therapy.

Exclusion Criteria18

• Diagnosed with pulmonary hypertension of WHO Group 2, 3, 4, or 5.
• Diagnosed with the following PAH subtypes of WHO Group 1: HIV-associated PAH, portal hypertension-associated PAH, schistosomiasis-associated PAH, PAH related to pulmonary veno-occlusive disease or pulmonary capillary hemangiomatosis, patients with PAH known to have a positive acute pulmonary vasoreactivity test.
• Poorly controlled hypertension after screening: seated systolic BP >160 mmHg or seated diastolic BP >100 mmHg, or pre-dose systolic BP <90 mmHg on C1D1.
• Pre-dose electrocardiogram (ECG) Fridericia-corrected QT interval (QTcF) ≥470 ms for men, ≥480 ms for women; or personal or family history of long QT syndrome (LQTS) or sudden cardiac death.
• Untreated mild or more severe obstructive sleep apnea.
• Previously underwent or plans to undergo heart or cardiopulmonary transplantation, or expected lifespan <12 months as assessed by the investigator.
• Diagnosed with chronic obstructive pulmonary disease (COPD) or other clinically significant lung disease.
• Evidence of interstitial lung disease (ILD) based on chest CT within 1 year before screening or pulmonary function test (PET) within 6 months before screening will lead to exclusion; if the above tests are not available, or chest CT within 1 year shows mild or greater ILD, a PET or chest CT should be performed during the screening period, and patients with evidence of ILD will be excluded.
• Pre-dose hemoglobin (Hb) above the sex-specific upper limit of normal (ULN) or <90 g/L, platelet count ≤100 × 10\^9/L, neutrophils <1.5 × 10\^9/L, aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >3 × ULN, total bilirubin >1.5 × ULN, estimated glomerular filtration rate (eGFR) <60 mL/min/1.73m\^2.
• History of portal hypertension or chronic liver disease, including Hepatitis B Surface Antigen (HBsAg) positive, and/or Hepatitis B Core Antibody (HBcAb) positive and Hepatitis Bvirus-Deoxyribonucleic acid HBV-DNA) titers outside the normal range; Hepatitis C virus (HCV) positive and hepatitis C virus ribonucleic acid (HCV-RNA) positive; Human Immunodeficiency Virus (HIV) seroresponse; Treponema pallidum antibody (TP-Ab) positive (if Treponema pallidum serology test is positive, further non-Treponema pallidum serology test, which is negative and judged by the investigator to be cured of syphilis in the past is eligible for inclusion).
• are participating in other clinical studies; or have participated in clinical studies of medical devices or other drugs within 30 days before screening (except for those who have only signed the ICF and have not received the investigational drug or device intervention), or are still within 5 half-lives (t1/2) of the investigational drug (whichever is longer).
• Previous treatment targeting the TGF-β superfamily (e.g., Sotatercept) (including participation in a clinical trial).
• Known participant has a prior allergy to macromolecular protein preparations/monoclonal antibodies, known hypersensitivity to the investigational drug or its excipients, or the same type of drug.
• History of opportunistic infection (e.g., invasive candidiasis or pneumocystis pneumonia within 6 months prior to dosing); Severe local infection (e.g., cellulitis, abscess) or systemic infection (e.g., sepsis) within 4 weeks prior to screening.
• History of malignancy or current malignancy (excluding basal cell carcinoma that has been resected with no evidence of metastatic disease for 3 years, or cervical intraepithelial neoplasia that has been treated and is not known to have recurred).
• History of chronic kidney disease prior to screening, or acute renal failure requiring acute dialysis within 3 months prior to screening, regardless of whether there was a previous history of kidney disease.
• Females who are pregnant or breastfeeding.
• Participants who are considered unsuitable for the study in the opinion of the investigator.