Ilofotase Alfa for Prevention of Renal Damage After Cardiac Surgery

Study Overview
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Brief Summary
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The aim of this clinical trial is to evaluate the efficacy and safety of two intravenous administrations of ilofotase alfa in patients at risk for renal damage following open heart surgery.

Detailed Description
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This is a Phase 2, multi-center, randomized, double-blind, placebo-controlled, 2-arm parallel group design trial in patients at risk for renal damage following open heart surgery. After screening and baseline assessments, eligible patients will be randomized 1:1 to either 2 doses of 128 mg ilofotase alfa, or 2 doses of placebo control. Randomization will be stratified by baseline eGFR and type of surgery. The patient will be treated with the investigational product (ilofotase alfa or placebo) at the same day before and after the surgery (Day 1). Follow-up clinic visits will be performed daily up to Day 5 for efficacy, safety, and pharmocokinetics assessments. A safety follow-up can be performed by telephone at Day 28. At Day 61, an end of trial visit will be done at site for efficacy, safety, and anti-drug antibodies assessments.

Official Title
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Double-Blind, Randomized, Placebo-Controlled Trial to Evaluate the Efficacy and Safety of Ilofotase Alfa in Patients at Risk for Renal Damage Following Open Heart Surgery

Conditions
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Open Heart Surgery, Renal Injury

Intervention / Treatment
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* Drug: Ilofotase alfa
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 years Planned for one of the following types of open chest cardiovascular surgery with the use of cardiopulmonary bypass pump (CPB): combined valve and CABG surgery CABG with 3 or more distal anastomoses Pre-operative eGFR ≥25 mL/min/1.73m2 and ≤65 mL/min/1.73m2 Female patients of childbearing potential agreeing to use effective contraception within IP treatment and 14 days thereafter Post-menopausal females (i.e., no menses for 12 consecutive months without an alternative medical cause with confirmatory follicle-stimulating hormone level of ≥40 mIU/mL) do not require contraception during the trial. Male patients agreeing to refrain from donating sperm, use a male condom when having sexual intercourse and in case their partner is of childbearing potential they must agree to use adequate and effective contraception method (see inclusion criterion 4) within IP treatment and 14 days thereafter The five most important Exclusion Criteria: Body weight ≤55 kg Known or suspected glomerulonephritis (other than diabetic kidney disease) or other systemic vasculitis Confirmed or treated endocarditis requiring antimicrobial or antiviral treatment within 30 days prior to surgery or other current active infection requiring antimicrobial or antiviral treatment within 14 days prior to surgery Known chronic liver disorder with Child-Pugh C classification Current planned (or scheduled) surgical intervention under conditions of circulatory arrest, including planned deep hypothermic circulatory arrest

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ilofotase alfa<br> | Drug: Ilofotase alfa<br>* After dilution of the concentrate, the investigational medicinal product will be administered by intravenous infusion for 1 hour at the same day before and after the surgery (Day 1)<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* After dilution of the concentrate, the investigational medicinal product will be administered by intravenous infusion for 1 hour at the same day before and after the surgery (Day 1)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of serum creatinine values | Ratio between the highest value postsurgery (post-surgery Day 1 and Days 2, 3, 4, and 5) and the pre-operative baseline value for serum creatinine | From Baseline to Day 5 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of adverse event (AE) and serious adverse event (SAE) occurrence |  | From Day -1 to Day 28 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Risk for renal damage following open heart surgery