BB3 is a small molecule with hepatocyte growth factor (HGF)-like activity that is entering Phase 3 clinical trials to limit delayed graft function in kidney transplant recipients, and entering Phase 2 clinical trials in cardiac surgery patients who develop acute kidney injury. The receptor for HGF is called c-Met. The HGF/c-Met pathway participates in the regulation of blood vessel formation, tissue repair and regeneration, and reducing deposition of extracellular matrix, a material produced in excess by injured tissues and causes organ dysfunction and fibrosis.
BB3 and renal transplantation
We have completed Phase 1 studies on BB3 in volunteers and patients, and conducted an interim analysis on a Phase 2 study in renal transplant patients at risk for delayed graft function (DGF) after receiving a suboptimal kidney.
In the Phase 2 study, patients were enrolled in the study post-transplant if they had low or no urine output. Three intravenous doses of BB3 were administered, the first dose given within 36 hours of transplant, and then 24 and 48 hours later. Renal function and other measures of severity of DGF were assessed over 28 days.
The primary endpoint was the time to produce 1.2 liter of urine in 24 hr, and secondary endpoints included serum creatinine, number of dialysis sessions, total daily urine output, number of acute rejection episodes, length of hospitalization, and effect on exploratory biomarkers.
The interim analysis showed that BB3:
- BB3 increased urine output and lowered serum creatinine
- BB3 reduced need for dialysis and shortened length of hospital stay
These observations will be confirmed and extended in our ongoing Phase 3 study, called GIFT (Graft Improvement Following Transplantation). Renal transplant recipients receiving a suboptimal kidney will be randomized to 3 IV doses of BB3 or placebo, administered daily started within 30 hours of transplant. About 152 patients will be enrolled. The primary endpoint is duration of dialysis. Secondary endpoints include other measures of renal function.
BB3 and acute kidney injury
Angion is also enrolling patients in a Phase 2 study on the ability of BB3 to treat acute kidney injury (AKI) in patients who undergo open heart surgery that uses cardiopulmonary bypass, also called a heart-lung machine. Patients with certain predisposing conditions such as existing kidney disease, previous cardiac surgery, compromised heart function, advanced age, and diabetes have a higher risk of kidney injury following surgery.
AKI is one of the most serious and frequent in-hospital complications and is associated with increased mortality, need for dialysis, longer length of hospital stay, an increased risk of infection, an increased incidence of chronic kidney disease, and therefore, increased costs to health systems. There is currently no FDA approved drug therapy for the prevention or treatment of AKI.
The Phase 2 study, called GUARD (GUard Against Renal Damage) is a multicenter, randomized, placebo-controlled, double-blind study involving approximately 100 patients in the U.S. that have risk factors for AKI.