Overview

This is a Phase Ib/IIa clinical study of IMC-003 treatment in pulmonary arterial hypertension (PAH) patients receiving background therapy

Eligibility

Inclusion Criteria:

1. Age screening between 18 and 75 years (inclusive), regardless of gender.
2. Patients diagnosed with WHO Group 1 pulmonary arterial hypertension (PAH) confirmed by right heart catheterization (RHC) before initial dosing (see Appendix 1), including the following subtypes: idiopathic PAH; heritable PAH; drug- or toxin-induced PAH; PAH associated with connective tissue diseases that is inactive; PAH associated with simple congenital heart defects with systemic-to-pulmonary shunts, at least one year post-correction surgery.
3. Symptomatic pulmonary arterial hypertension, WHO functional class II or III.
4. Must also meet the following hemodynamic criteria: mean pulmonary arterial pressure (mPAP) ≥25 mmHg at rest; pulmonary artery wedge pressure (PAWP) ≤15 mmHg.
5. Pulmonary vascular resistance (PVR) ≥5 Wood Units (400 dyn·sec·cm-5) by RHC before the first dose, results from pre-screening RHC are acceptable (if they meet the study requirements).
6. Receiving stable doses of background PAH therapy (i.e., each therapy's individualized target dose has been achieved and stable for at least 90 days before initial dosing).
7. Six-minute walk distance (6MWD) during screening ≥150 meters and ≤450 meters.
8. Female participants of childbearing potential must have a negative serum pregnancy test before dosing and agree to undergo regular urine or serum pregnancy tests (any one) during the treatment period; agree to use highly effective contraception before dosing, during the treatment period (including dosing interruptions), and for 16 weeks (112 days) after the last dose, and to avoid blood donation or egg donation within 16 weeks (112 days) after the last dose.
9. Male participants agree to use condoms, defined as using latex condoms or non-latex (non-animal membrane) condoms (e.g., polyurethane) during sexual intercourse with pregnant or childbearing potential women during treatment (including dosing interruptions) and for 16 weeks (112 days) after the last dose, even if a successful vasectomy has been performed, and to avoid sperm donation within this period.
10. Participants understand and comply with the study procedures, voluntarily participate, and sign the informed consent form.

Exclusion Criteria:

1. Diagnosed with pulmonary hypertension of WHO Group 2, 3, 4, or 5.
2. 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.
3. 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.
4. 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.
5. Untreated mild or more severe obstructive sleep apnea.
6. Previously underwent or plans to undergo heart or cardiopulmonary transplantation, or expected lifespan \<12 months as assessed by the investigator.
7. Diagnosed with chronic obstructive pulmonary disease (COPD) or other clinically significant lung disease.
8. 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.
9. 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.
10. 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).
11. 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).
12. Previous treatment targeting the TGF-β superfamily (e.g., Sotatercept) (including participation in a clinical trial).
13. 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.
14. 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.
15. 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).
16. 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.
17. Females who are pregnant or breastfeeding.
18. Participants who are considered unsuitable for the study in the opinion of the investigator.