A Study to Evaluate the Safety and Efficacy of AC607 for the Treatment of Kidney Injury in Cardiac Surgery Subjects

Study Overview
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Brief Summary
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Subjects entering the study will have undergone cardiac surgery. Those who experience kidney injury within 48 hours of their surgery will be enrolled into the study. Once enrolled, subjects will receive a single administration of AC607 or placebo. Kidney recovery will be evaluated over the subsequent 30 days and death or the need for dialysis will be evaluated within 90 days of dosing. After 90 days (evaluation period), subjects will enter a 3-year extension phase of the study to monitor safety and long-term outcomes (follow-up period).

Detailed Description
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The study will enroll post-cardiac surgery subjects (CABG and/or valve) with laboratory evidence of AKI within 48 hrs of removal from cardiopulmonary bypass. Subjects will be randomly assigned (1:1 ratio) to treatment with a single administration of AC607 or placebo (approximately 100 subjects per group). Safety and efficacy assessments will be performed daily during the post-operative hospital stay from the day randomized into the study until discharge, at 30 days, and at 90 days after study drug administration (evaluation phase). Safety and long-term clinical outcomes will be assessed at 6, 12, 24 and 36 months (long-term follow-up phase).

Official Title
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A Randomized, Multicenter, Double-Blind, Placebo-Controlled Study of AC607 for the Treatment of Acute Kidney Injury in Cardiac Surgery Subjects

Conditions
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Acute Kidney Injury

Intervention / Treatment
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* Biological: AC607
* Biological: Vehicle Only


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 21 years Had cardiovascular surgery utilizing cardiopulmonary bypass Have a pre-operative (baseline) serum creatinine value collected within 30 days of surgery (if multiple laboratory results are available within this time window, the most recent serum creatinine value prior to surgery will be used to establish the baseline) Willing and able to comply with visit schedule and study procedures including post-hospitalization discharge follow-up Ability to give informed consent or have a legally acceptable representative do so for them Have AKI defined as ≥ 0.5 mg/dL rise in serum creatinine from baseline within 48 hours of removal from cardiopulmonary bypass Exclusion Criteria: Active cancer and/or receiving active treatment for cancer, with the exception of squamous cell or basal cell carcinoma of the skin Had surgery for thoraco-abdominal aortic aneurysm (TAAA) Currently participating in another interventional drug or device clinical study Prisoner or other detainee Has a current medical condition that would preclude or compromise femoral artery catheter placement Has an intra-aortic balloon pump (IABP) in place within 2 hours of catheter placement Has a ventricular assist device (VAD) or extracorporeal membrane oxygenation (ECMO) in place at the time of the study catheter placement Prior history of solid organ or bone marrow transplant Stage 5 CKD or currently on dialysis Are expected to receive dialysis within 24 hours of enrollment or dosing Had a complication during surgery or post-operatively that, in the opinion of the principal investigator (PI), significantly increases the risk of complications to the subject and therefore precludes dosing the subject Are pregnant or lactating. A woman with child-bearing potential may be tested for pregnancy at the discretion of the PI.

Ages Eligible for Study
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Minimum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: AC607<br>Treatment with AC607 | Biological: AC607<br>* AC607 will be a single administration at a target dose of 2 x 10E6 hMSC/kg body weight<br>* Other names: stem cells;|
| Placebo Comparator: Placebo<br>Treatment with Placebo | Biological: Vehicle Only<br>* The dose will be calculated and recorded in the same way as for AC607.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Kidney Recovery defined as a post-operative serum creatinine return to pre-operative baseline values. | The first occurrence of a post-dosing serum creatinine level that is equal to or less than the subject's pre-operative baseline level. | Within 30 days of dosing. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All-Cause Mortality or Dialysis (composite endpoint). |  | Subjects who died or received dialysis within 30 and 90 days after dosing. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute Kidney Injury, Acute renal failure, Human mesenchymal stem cells, Allogeneic stem cells