Clinical Trial: Study to Prevent Acute Kidney Injury After Cardiac Surgery Involving Cardiopulmonary Bypass

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: A Multicenter, Prospective, Parallel-Group, Double-Blind, Randomized, Placebo-Controlled, Phase 2 Study of BB3 to Assess the Safety and Efficacy of BB3 in Patients Developing Acu

Brief Summary: The objective of the study is to assess the safety and efficacy of BB3 in preventing AKI compared to placebo when administered to patients at risk for developing acute kidney injury (AKI) following cardiac surgical procedures involving cardiopulmonary bypass (CPB).

Detailed Summary:

Angion Biomedica Corp. has developed a small molecule hepatocyte growth factor/scatter factor (HGF/SF) mimetic, termed BB3, which exerts significant nephroprotective effects in several preclinical renal injury models. Angion intends to develop BB3 as a therapy to prevent and/or treat acute kidney injury. BB3 is a new molecular entity and the proposed treatment is novel since no drug is currently available with an indication to prevent and/or treat acute kidney injury.

This is a randomized, prospective, parallel-group, double-blind, placebo-controlled, multicenter study. Patients who will be undergoing a surgical procedure involving CPB and are at elevated risk pre-surgery for AKI will be eligible to participate in the study. Patients will be randomized 1:1 to receive either BB3 or placebo (normal saline) immediately after surgery. Study drug will be administered for a total of 4 daily intravenous (IV) infusions. The first post-operative dose MUST be started within 4 hours of completing CPB. The second dose will be administered 24 ± 2 hours after completing CPB, and the third and fourth doses will be administered 24 ± 2 hours after each previous dose.

Patients will be followed for safety, PK (in a subset of patients), and efficacy up to Day 90, with Day 1 being the day of the first infusion of study drug. Patients will be assessed daily through Day 7 and then on Days 14, 30 and 90.

Efficacy endpoints include assessment of post-CPB renal injury, expressed as percent increase in sCr above Baseline over time and the maximum percent increase in sCr following CPB, from 24 hours after end of CPB through Day 5; the proportion of patients reaching each KDIGO stage or having no AKI at specified time points through Day 30; and analyses among patients who develop AKI assessin
Sponsor: Angion Biomedica Corp

Current Primary Outcome: The mean AUC of the percent increase in serum creatinine above baseline [ Time Frame: starting from 24 hr after the end of CPB through Day 5 ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

  • The maximum percent increase in sCr level from baseline [ Time Frame: Day 5 ]
  • The mean percent increase in serum creatinine above baseline over time [ Time Frame: starting from the end of CPB through Day 5, through Day 7, through Day 14, and through Day 30 ]
  • The mean percent increase of sCr above baseline [ Time Frame: at 24 hr after the end of CPB, and at Day 3, Day 4, Day 5, and Day 7 ]
  • The proportion of subjects who are diagnosed with AKI per KDIGO criteria [ Time Frame: through Day 5 ]
  • The proportion of subjects who are diagnosed with AKI per KDIGO criteria [ Time Frame: through Day 7 ]
  • Proportion of patients by severity of renal injury using KDIGO AKI staging [ Time Frame: at 24 hr after the end of CPB, at Day 3, at Day 4, Day 5, Day 7, Day 14, and Day 30 ]
  • The proportion of patients with AKI [ Time Frame: at 24 hr after the end of CPB, Day 3, Day 4, Day 5, Day 7 ]
  • Time in days from end of CPB to occurrence of AKI [ Time Frame: within Days 1-5 and within Days 1-7 ]
  • Time in days from the occurrence of AKI diagnosed postoperatively through Day 5 to recovery from AKI and through Day 7 to recovery from AKI [ Time Frame: through Day 5 to recovery from AKI and through Day 7 to recovery from AKI ]
  • Time in days to improvement in renal function [ Time Frame: from the day of occurrence of AKI diagnosed postoperatively through Day 5 and through Day 7 ]
  • the proportion of patients with renal function recovery, progression, or stabilization among patients with AKI diagnosed postoperatively [ Time Frame: at Day 30 ]
  • Among patients with AKI diagnosed postoperatively, the proportion of patients with renal function recovery, progression, or stabilization [ Time Frame: Through day 5 ]
  • The slope of decline of the creatinine curve [ Time Frame: from the day of peak sCr through Day 5, Day 7, Day 14 and Day 30 ]
  • Proportion of patients requiring initiation of any form of renal replacement therapy [ Time Frame: up to Day 30 ]
  • Length of index hospital stay [ Time Frame: through Day90 ]
  • Proportion of patients developing a composite endpoint comprising the following events: death, worsening of kidney function [ Time Frame: during the 30-day and 90-day post-operative periods ]
  • Changes from baseline in eGFR [ Time Frame: at Days 4, 7, 14, 30 and 90 ]
  • Proportion of patients having a ≥ 20 % reduction from baseline in eGFR [ Time Frame: at Days 2, 3, 4, 7, 14, and 30 and 90 ]
  • Maximal change from baseline in eGFR and sCr [ Time Frame: through Day 90 ]
  • Changes in circulating or urinary biomarkers of renal injury [ Time Frame: through Day 90 ]
  • Urine volume over 12-hour periods [ Time Frame: for the first 72 hours post-CPB ]
  • Cmax [ Time Frame: pre-dose, immediately after completing the 4th infusion, and at 2 hours and at 6 hours from the start of the 4th infusion ]
  • AUC [ Time Frame: pre-dose, immediately after completing the 4th infusion, and at 2 hours and at 6 hours from the start of the 4th infusion ]
  • Relationship of post-first infusion BB3 blood levels with the primary and secondary endpoints set forth above. [ Time Frame: Day 1 ]


Original Secondary Outcome:

  • The maximum percent increase in sCr level from baseline [ Time Frame: Day 5 ]
  • The mean percent increase in serum creatinine above baseline over time [ Time Frame: starting from the end of CPB through Day 5, through Day 7, through Day 14, and through Day 30 ]
  • The mean percent increase of sCr above baseline [ Time Frame: at 24 hr after the end of CPB, and at Day 3, Day 4, Day 5, and Day 7 ]
  • The proportion of subjects who are diagnosed with AKI per KDIGO criteria [ Time Frame: through Day 5 ]
  • The proportion of subjects who are diagnosed with AKI per KDIGO criteria [ Time Frame: through Day 7 ]
  • Proportion of patients by severity of renal injury using KDIGO AKI staging [ Time Frame: at 24 hr after the end of CPB, at Day 3, at Day 4, Day 5, Day 7, Day 14, and Day 30 ]
  • The proportion of patients with AKI [ Time Frame: at 24 hr after the end of CPB, Day 3, Day 4, Day 5, Day 7 ]
  • Time in days from end of CPB to occurrence of AKI [ Time Frame: within Days 1-5 and within Days 1-7 ]
  • Time in days from the occurrence of AKI diagnosed postoperatively through Day 5 to recovery from AKI and through Day 7 to recovery from AKI [ Time Frame: through Day 5 to recovery from AKI and through Day 7 to recovery from AKI ]
  • Time in days to improvement in renal function [ Time Frame: from the day of occurrence of AKI diagnosed postoperatively through Day 5 and through Day 7 ]
  • the proportion of patients with renal function recovery, progression, or stabilization among patients with AKI diagnosed postoperatively [ Time Frame: at Day 30 ]
  • Among patients with AKI diagnosed postoperatively, the proportion of patients with renal function recovery, progression, or stabilization [ Time Frame: Through day 5 ]
  • The slope of decline of the creatinine curve [ Time Frame: from the day of peak sCr through Day 5, Day 7, Day 14 and Day 30 ]
  • Proportion of patients requiring initiation of any form of renal replacement therapy [ Time Frame: up to Day 30 ]
  • Length of index hospital stay [ Time Frame: through Day90 ]
  • Proportion of patients developing a composite endpoint comprising the following events: death, worsening of kidney function [ Time Frame: during the 30-day and 90-day post-operative periods ]
  • Changes from baseline in eGFR [ Time Frame: at Days 4, 7, 14, 30 and 90 ]
  • Proportion of patients having a ≥ 20 % reduction from baseline in eGFR [ Time Frame: at Days 2, 3, 4, 7, 14, and 30 and 90 ]
  • Maximal change from baseline in eGFR and sCr [ Time Frame: through Day 90 ]
  • Changes in circulating or urinary biomarkers of renal injury [ Time Frame: through Day 90 ]
  • Urine volume over 12-hour periods [ Time Frame: for the first 72 hours post-CPB ]
  • Cmax [ Time Frame: pre-dose, immediately after completing the 4th infusion, and at 2 hours and at 6 hours from the start of the 4th infusion ]
  • AUC [ Time Frame: pre-dose, immediately after completing the 4th infusion, and at 2 hours and at 6 hours from the start of the 4th infusion ]


Information By: Angion Biomedica Corp

Dates:
Date Received: April 18, 2016
Date Started: December 2016
Date Completion: March 2018
Last Updated: January 17, 2017
Last Verified: January 2017