Ribo (HongKong) Life Science Limited

Main study objectives 1) To determine the maximum tolerated dose (MTD) and phase II recommended dose (RP2D) of ISIS 560131 in Chinese patients with AR V7-positive mCRPC. 2) To preliminarily evaluate the efficacy of ISIS 560131 in Chinese patients with AR V7-positive mCRPC. Secondary study objectives 1) To evaluate the safety and tolerability of ISIS 560131 in patients with AR V7-positive mCRPC; 2) To evaluate the pharmacokinetic characteristics of ISIS 560131 in patients with AR-V7-positive mCRPC; 3) To evaluate the immunogenicity of ISIS 560131; 4) To preliminarily analyze the PK/PD relationship of ISIS 560131 in patients with AR-V7-positive mCRPC. Other research objectives 1) If data permit, analyze AR receptor expression and drug inhibition of signaling pathway regulatory genes; and the consistency of different detection methods for AR-V7; 2) If data permit, characterize the PK characteristics of ISIS 560131 in Chinese AR-V7-positive mCRPC patients based on population pharmacokinetic (PopPK) analysis methods; 3) If data permit, evaluate the relationship between ISIS 560131 exposure in humans and efficacy and adverse events.

To compare the change in HbA1c from baseline between the ISIS 449884 injection 75 mg treatment group and the placebo group after 16 weeks of double-blind treatment with subcutaneous injection once a week; To evaluate the safety and tolerability of IS449884 injection 75 mg subcutaneous injection once a week for 16 weeks compared with placebo

1. To compare the changes in glycated hemoglobin (HbA1c) compared with baseline between the ISIS 449884 injection 50 mg, 60 mg or 100 mg treatment group combined with metformin and the placebo group combined with metformin after 16 weeks of double-blind treatment with subcutaneous injection once a week or every other week. 2. To evaluate the safety and tolerability of ISIS 449884 injection 50 mg or 60 mg once a week or 100 mg once every other week subcutaneous injection combined with metformin for 16 weeks compared with placebo combined with metformin.