Ilofotase Alfa for Prevention of Renal Damage After Cardiac Surgery

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

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.

Study Overview

• Status: Recruiting
• Conditions: Open Heart Surgery
• Intervention / Treatment: Drug: Ilofotase alfa; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Hof; Phone Number: +31302289222; Email: CSA-RD.phase2@am-pharma.com

Study Locations

• Germany
  • Munich, Germany
    • Recruiting
    • Research Site
    • Contact: JF Bohm

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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. combined valve and CABG surgery
   2. CABG with 3 or more distal anastomoses
3. Pre-operative 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 (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.

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; 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)
Experimental: Ilofotase alfa	Drug: Ilofotase alfa; 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)

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC of AKI	The area under the curve (AUC) of AKI (kidney disease improving global outcomes [KDIGO] sCreat), defined as duration (in days) and severity of AKI; measured over the first 5 days after surgery	From Day 1 to Day 5
Assessment of major adverse kidney events (MAKE) 60	Major adverse kidney events (MAKE) 60, defined as died up to and including Day 61, have received or are receiving new renal replacement therapy (RRT) up to and including Day 61, or have a decrease in estimated glomerular filtration rate (eGFR) ≥25% on Day 61 compared to the pre-operative eGFR reference value	Daily post-surgery through Day 5
Assessment of surgery-related complications occurrence	Postoperative surgery-related complications within 28 days of surgery, assessed according to the Society of Thoracic Surgeons (STS) definition	From Day 1 to Day 28
Assessment of length of stay in the intensive care unit	Length of stay in the intensive care unit (ICU) in days after the initial surgery	From Baseline to Day 28
Investigation of biomarkers of AKI (optional after the end of the trial)	Changes in biomarkers of AKI (urine and blood) compared to Baseline: sCreat, cystatin C and potentially further biomarkers of AKI	Pre-operative Baseline, Day 1 post-surgery, Day 2, Day 3, Day 4, Day 5, and Day 61
Serum levels of ilofotase alfa	Population (Pop) PK	Day 1 postsurgery, Day 2, Day 3, Day 4, and Day 5

Collaborators and Investigators

• Sponsor: AM-Pharma
• Collaborators: FGK Clinical Research GmbH
• Investigators: Principal Investigator: Pickkers, Prof, MD, PhD, Radboud University Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): December 19, 2023
• Primary Completion (Estimated): November 15, 2024
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: December 5, 2023
• First Submitted That Met QC Criteria: December 5, 2023
• First Posted (Actual): December 13, 2023

Study Record Updates

• Last Update Posted (Actual): February 15, 2024
• Last Update Submitted That Met QC Criteria: February 14, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: CABG; Kidney; Cardiac; Renal; CPB
• Other Study ID Numbers: AP-recAP-CSA-RD-02-01; WHO Universal Trial Number (Registry Identifier: U1111-1295-0827); EU Clinical Trial Number (Registry Identifier: 2023-505859-45)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No