Clinical trial NCT06168799: Ilofotase Alfa for Prevention of Renal Damage After Cardiac Surgery
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Open Heart Surgery
Keywords: Renal
Kidney
Cardiac
CPB
CABG
Lead sponsor: AM-Pharma
Sponsor class: INDUSTRY
Collaborators: name: FGK Clinical Research GmbH
First posted: 2023-12-13
Enrollment: 250
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: Inclusion Criteria:

1. Age ≥18 years
2. Planned for one of the following types of open chest cardiovascular surgery with the use of cardiopulmonary bypass pump (CPB):

   1. 1. combined valve and CABG surgery; 2. aortic valve plus aortic root and/or ascending aorta (excluding aortic arch)
   2. CABG with 3 or more distal anastomoses
3. Screening eGFR ≥25 mL/min/1.73m2 and ≤65 mL/min/1.73m2
4. Female patients of childbearing potential agreeing to use effective contraception within IP treatment and 14 days thereafter

   Post-menopausal females do not require contraception during the trial.
5. 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:

1. Body weight ≤55 kg
2. Known or suspected glomerulonephritis (other than diabetic kidney disease) or other systemic vasculitis
3. 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
4. Known chronic liver disorder with Child-Pugh C classification
5. Current planned (or scheduled) surgical intervention under conditions of circulatory arrest, including planned deep hypothermic circulatory arrest

Primary outcomes:
measure: Assessment of serum creatinine values
timeFrame: From Baseline to Day 5
Secondary outcomes:
measure: Assessment of adverse event (AE) and serious adverse event (SAE) occurrence
timeFrame: From Day -1 to Day 28
Other outcomes:
measure: AUC of AKI
timeFrame: From Day 1 to Day 5
measure: Assessment of surgery-related complications occurrence
timeFrame: From Day 1 to Day 28
measure: Assessment of length of stay in the intensive care unit
timeFrame: From Baseline to Day 28
measure: Serum levels of ilofotase alfa
timeFrame: Day 1 postsurgery, Day 2, Day 3, Day 4, and Day 5
measure: Assessment of major adverse kidney events (MAKE) 60
timeFrame: Daily post-surgery through Day 5
measure: Investigation of biomarkers of AKI (optional after the end of the trial)
timeFrame: Pre-surgery Baseline, Day 1 post-surgery, Day 2, Day 3, Day 4, Day 5, and Day 61
Locations:
city: Munich
country: Germany
facility: Research site
Study officials:
affiliation: Radboud University Medical Center
name: Pickkers, Prof, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: