A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Study to Assess The Effects of Intravenous BG9928 on Body Weight in Subjects with Acute Decompensated Heart Failure and Renal Insufficiency

The Trident-1 study is an International multi-center, randomized, double-blind, placebo controlled phase 3 clinical trial with plans to randomise a total of 900 patients. The purpose of the study is to determine the effects and safety on the body weight of 3 different doses of BG9928 (0.03 mg/kg, 0.15 mg/kg, or 0.3 mg/kg) and placebo given up to a maximum 5 days to subjects hospitalized due to Acute Decompensated Heart Failure (ADHF) and Renal Insufficiency. BG9928 is a A1 receptor antagonist, which from previous studies have demonstrated ability to preserve renal function and promote urine production. The effect of BG9928 on body weight is thus related to the urine output. The study drug will be given in addition to the medication that would normally be given to ADHF patients. This means that patients on placebo still receive normal standard care. The primary objective of the study is to determine the effect of BG9928, when added to standard therapy, on the change in body weight at 24 hours following the first dose in these subjects. The secondary efficacy objectives of this study are to determine the effect of BG9928, when added to standard therapy, on worsening renal function during the treatment period, the number of days of hospital-free survival (DHFS), the improvement in Dyspnea Symptom and Edema Score, Subject Global Clinical Assessments and Physician Global Clinical Assessment. Additionally the secondary efficacy objectives are measuring the use of concomitant medications to treat heart failure, length of hospital stay, cardiovascular and all-cause mortality and re-hospitalization up to 180 days after the initial dose. The safety objective of the study is to assess the safety and tolerability of BG9928. Upon screening patients will be randomized evenly into either of the 4 treatment arms and will receive IV study drug infusions twice daily for a maximum treatment period of 5 days 910 doses). Prior to and during hospitalisation period, for a maximum of 7 days, the patients will be monitored via physical exam, vital signs, body weight, ECG diagram, questionnaires, blood samples (including pregnancy test for women of childbearing potential, haematology, chemistry, special kidney tests (BNP, Cystatin C), bone markers ,genetic and PK testing. Safety monitoring and concomitant medication monitoring will be conducted from screening and up to day 30 . Telephone follow-up done at 2, 3 and 6 months after the first study dose.