Ilofotase alfa for prevention of renal damage after cardiac surgery

Overview

Sponsor-declared trial summary

Key facts

Sponsor

AM-Pharma B.V.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Female Urogenital Diseases and Pregnancy Complications [C13], Diseases [C] - Male Urogenital Diseases [C12]

Trial duration

19 Dec 2023 → 4 Dec 2025

Decision date (initial)

2023-12-12

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

AM-Pharma B.V.

External identifiers

EU CT number

2023-505859-45-00

WHO UTN

U1111-1295-0827

ClinicalTrials.gov

NCT06168799

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To assess the effect of ilofotase alfa on renal function

Secondary objectives 2

1. Safety: To assess the safety and tolerability of ilofotase alfa in patients undergoing open chest heart surgery
2. Efficacy: To assess the effect of treatment with ilofotase alfa on the clinical outcome in patients undergoing cardiac surgery

Conditions and MedDRA coding

Risk for renal damage following open heart surgery

Study design 1 period

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration, European Medicines Agency

Plan to share IPD

No

IPD plan description

IPD will not be shared.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

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): a. 1) combined valve and CABG surgery 2) aortic valve plus aortic root and/or ascending aorta (excluding aortic arch) b. CABG with 3 or more distal anastomoses
3. Screening eGFR ≥25 mL/min/1.73m2 and ≤65 mL/min/1.73m2 (calculated at Screening using sCreat which can be maximally 28 days old and the 2021 CKD-EPI formula without race correction (eGFR = 142 × Min(Scr/κ,1)α × Max(Scr/κ,1)-1.200 × 0.9938Age [× 1.012 if female])
4. Female patients of childbearing potential agreeing to use an effective contraception method within IP treatment and 14 days thereafter. Post-menopausal females (i.e., >60 years of age or 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

Exclusion criteria 22

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
6. Planned surgery for aortic dissection
7. Use of left ventricular assist device (LVAD), or intra-aortic balloon pump or other cardiac devices, within 7 days prior to surgery
8. Received any investigational drug within 30 days or 5 half-lives (whichever is longer) prior to Day 1 or planned or current participation in another interventional study until the EoT visit has been completed
9. Previous receipt of ilofotase alfa
10. Not willing and able to understand the information on the nature, the scope, and the relevance of the trial and to provide voluntary, written informed consent to participate in the trial before any trial related procedures
11. Pregnant or nursing women
12. Known or suspected hypersensitivity to ilofotase alfa or any components of the formulation used
13. Any previous organ transplantation
14. Congenital heart disease
15. Diagnosed with AKI (as defined by KDIGO criteria) within 3 months prior to surgery
16. History of RRT
17. Cardiogenic shock or hemodynamic instability which require inotropes or vasopressors or other mechanical devices such as intra-aortic balloon counter-pulsation (IABP) within 24 hours prior to surgery
18. A requirement for any of the following within one week prior to surgery: implantation of a defibrillator or permanent pacemaker, mechanical ventilation, IABP, LVAD, other forms of mechanical circulatory support
19. Required cardiopulmonary resuscitation within 14 days prior to cardiac surgery
20. Ongoing sepsis (as defined by SEPSIS-3, the Third International Consensus Definitions for Sepsis and Septic Shock) within the past 2 weeks or, in the opinion of the investigator, an untreated diagnosed clinically significant infection (viral or bacterial) prior to or at Screening and before randomization
21. Medical condition which requires active immunosuppressive treatment (daily steroid doses of ≤10 mg are allowed)
22. Employees or relatives of the sponsor or the investigator

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Ratio between the highest value post-surgery (post-surgery Day 1 and Days 2, 3, 4, and 5) and the pre-surgery baseline value for serum creatinine (sCreat)

Secondary endpoints 2

1. Incidence rate of adverse events (AEs) and serious AEs through Day 28
2. 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-surgery baseline eGFR reference value

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

AM-Pharma B.V.

Sponsor organisation

AM-Pharma B.V.

Address

Stadsplateau 7

City

Utrecht

Postcode

3521 AZ

Country

Netherlands

Scientific contact point

Organisation

AM-Pharma B.V.

Contact name

Clinical trial information

Public contact point

Organisation

AM-Pharma B.V.

Contact name

Clinical trial information

Third parties 7

Locations

3 EU/EEA countries · 10 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 22 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

7 submissions — initial application plus substantial / non-substantial modifications