An Trial of Two Dosing Regimens of AP214 for the Prevention of Kidney Injury in Patients Undergoing Cardiac Surgery

Study Overview
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Brief Summary
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This study investigates the effect of two dose-levels of AP214 on the prevention of (acute) kidney injury after cardiac surgery.

Official Title
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An Explorative Phase 2, Randomized, Double-Blind, Placebo-Controlled, Safety and Efficacy Trial of Two Dosing Regimens of AP214 for the Prevention of Kidney Injury in Patients Undergoing Cardiac Surgery

Conditions
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Cardiac Surgery, Coronary Artery Bypass, Aortic Aneurysm, Valve Surgery, Kidney Diseases

Intervention / Treatment
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* Drug: AP214
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Has signed the trial-specific informed consent form. Patients ≥ 18 years old, male or female, not of childbearing potential (postmenopausal or permanently sterilized, e.g. tubal ligation, hysterectomy, bilateral salpingectomy), regardless of ethnicity. Patients undergoing combined coronary artery bypass grafting (CABG) surgery and surgery of one or more cardiac valve (valve(s) surgery), or Patients undergoing surgery of more than one cardiac valve (valves surgery), or Patients undergoing surgery of the aortic root or ascending part of the aorta, or Patients undergoing surgery of the aortic root or ascending part of the aorta, combined with CABG and/or valve(s) surgery, or Patients with stage III chronic kidney disease (eGFR 30-59 ml/min determined by the Modification of Diet in Renal Disease (MDRD formula)) undergoing CABG or Valve surgery Exclusion Criteria: Cardiac surgery to be performed off pump without cardiopulmonary bypass. Cardiac surgery to be performed with hypothermic circulatory arrest. Confirmed or suspected endocarditis. EF ≤ 20%, evaluated within 2 months prior to screening visit. Requiring a reoperation on one of the valves within 3 months following the original valve surgical procedure. Active peptic ulcer disease and gastritis. Receiving dopamine, adrenalin or noradrenalin at any dose at any time 14 days prior to Day of surgery. Known or suspected hypersensitivity to the investigational medicinal product. Current participation in any other interventional clinical trial. Previously dosed with AP214. Use of investigational medicinal products within the previous 6 months. Body weight above 130 kg. History of any organ transplant. Women who are of childbearing potential, pregnant, or breast-feeding. Current abuse of alcohol or substance, according to the investigator's medical judgment. Has a mental incapacity or language barriers precluding adequate understanding of trial procedures. Any history of cancer within the last 2 years Any history of dialysis. Is considered by the Investigator unsuitable to participate in the trial for any other reason, for instance due to a significant serious underlying condition.

Ages Eligible for Study
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Minimum Age: 18 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AP214; dose-level 1<br>AP214; dose-level 1 | Drug: AP214<br>* AP214<br>|
| Experimental: AP214; dose-level 2<br>AP214; dose-level 2 | Drug: AP214<br>* AP214<br>|
| Placebo Comparator: Placebo to AP214<br>Placebo | Drug: Placebo<br>* Placebo; intravenous infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and Tolerability | To assess the safety and tolerability of AP214 compared to placebo; by analysis of number and nature of Adverse Events (AEs), Serious Adverse Events (SAEs), changes in laboratory parameters and overall health status | 90 days | 
| Efficacy | To assess the effect of AP214 versus placebo on the maximal postoperative change in absolute values of Serum Creatinine (SCr) compared to baseline within the first 7 days after surgery or until discharge from hospital, whichever comes first | 7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy | To assess the ability of AP214 compared to placebo to reduce postoperative changes in SCr, and eGFR at day 28, 60 and Day 90 and GFR at Day 90 compared to baseline | 90 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cardiac surgery, Acute kidney injury