Ilofotase Alfa for Prevention of Renal Damage After Cardiac Surgery

Open Heart Surgery Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06168799
• Other study ID #: AP-recAP-CSA-RD-02-01
• Secondary ID: WHO Universal Tr
• Status: Recruiting
• Phase: Phase 2
• Start date: December 19, 2023
• Est. completion date: December 31, 2024

Study information

• Verified date: February 2024
• Source: AM-Pharma
• Contact: Hof
• Phone: +31302289222
• Email: CSA-RD.phase2[@]am-pharma.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 150
• Est. completion date: December 31, 2024
• Est. primary completion date: November 15, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Open Heart Surgery

Intervention

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)
• 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)

Locations

Country	Name	City	State
Germany	Research site	Munich

Sponsors (2)

Lead Sponsor	Collaborator
AM-Pharma	FGK Clinical Research GmbH

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	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
Other	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
Other	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
Other	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
Other	Serum levels of ilofotase alfa	Population (Pop) PK	Day 1 postsurgery, Day 2, Day 3, Day 4, and Day 5
Primary	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	Assessment of adverse event (AE) and serious adverse event (SAE) occurrence		From Day -1 to Day 28