Efficacy and Safety of Corline Heparin Conjugate for Improving Kidney Graft Function in Deceased-Donor Renal Transplant Recipients: A Phase 2 Randomized Controlled Trial
- Trial ID
- 2022-501389-23-02
- Protocol
- RENAPAIR 02
- Sponsor
- Corline Biomedical AB
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the effect of **Renaparin** on graft function in renal transplant patients at high risk of ischemia-reperfusion injury (IRI) and delayed graft function (DGF). These patients have received a kidney preserved in static cold storage (SCS) from a deceased donor that meets the criteria for donation after brain death-expanded criteria donor (DBD-ECD) or donation after circulatory death (DCD). This is clinically relevant as improving graft function in such high-risk patients can significantly enhance transplant outcomes and reduce complications associated with IRI and DGF.
Secondary objectives include: - Assessing the safety and tolerability of **Renaparin** in renal transplant patients. - Evaluating the uptake of **Renaparin** on the kidney vascular endothelium during cold storage. These objectives are crucial for understanding the broader implications of **Renaparin** use in organ preservation and its potential impact on patient safety and transplant success.
Participants
The clinical trial involves a total of **28 participants** who are patients with **end-stage renal disease** or otherwise insufficient kidney function. The study population includes both male and female subjects aged between 18 and 75 years. Participants are dialysis-dependent and have been identified as suitable candidates for kidney transplantation. The trial population was selected based on specific criteria, including the requirement for the kidney to be sourced from a deceased donor, either after brain death or circulatory death. Participants must weigh between 45 and 115 kg and have a negative crossmatch test prior to transplantation, with no evidence of donor-specific antibodies. Female participants are required to be post-menopausal, surgically sterile, or using effective contraception methods during the study treatment. The trial does not include a vulnerable population, and all participants are required to provide informed consent. Lifestyle considerations such as diet and physical activity are not specified in the available data.
Plans and Procedures
The clinical trial is a **phase 2**, single-blind, randomized, no-treatment controlled study designed to evaluate the efficacy and safety of **Renaparin** for improving kidney graft function in deceased-donor transplant recipients. The trial targets patients with **end-stage renal disease** or insufficient kidney function who are at high risk of ischemia-reperfusion injury and delayed graft function. The study will span a total duration of 12 months, consisting of a 3-month treatment phase followed by a 9-month follow-up period. Participants will be randomly assigned to receive either the investigational product or no treatment, with the primary endpoint being the estimated glomerular filtration rate (eGFR) at Month 3, calculated using the MDRD 4 equation.
The trial will commence with an inclusion (screening) visit to assess eligibility based on specific criteria, including age, dialysis dependency, and donor kidney characteristics. Eligible participants will be required to attend multiple study visits, including follow-up visits on Days 1-7, Day 30, and at Months 3, 6, and 12. These visits will involve assessments of secondary endpoints such as serum creatinine levels, incidence and severity of delayed graft function, and urine output. The end-of-study visit will occur at Month 12, marking the conclusion of participant involvement.
Participant involvement is expected to last approximately 12 months, with conditions for early termination including withdrawal of consent, adverse events, or non-compliance with study procedures. The study aims to provide valuable insights into the potential benefits of Renaparin in enhancing kidney graft outcomes, with the ultimate goal of improving patient care in renal transplantation.
Treatment
The clinical trial involves the use of **Renaparin**, an experimental medication formulated as a **solution for organ preservation**. The active substance in Renaparin is **Corline Heparin Conjugate**, a polymer-based compound. This solution is specifically designed for external use in the preservation of organs, particularly kidneys, during transplantation procedures. The maximum daily dose and total dose of Renaparin is 100 mg, administered over a maximum treatment period of one day. The solution is applied externally to the organ to be preserved, ensuring optimal conditions for transplantation. Renaparin is not formulated for pediatric use and is designated as an orphan drug under the designation number EU/3/14/1332.
In addition to the experimental treatment, the study may involve the use of a non-experimental **anticoagulant solution** as part of the standard organ preservation protocol. This comparator treatment is utilized to maintain consistency with standard-of-care practices in organ transplantation. The anticoagulant solution is not the primary focus of the study but serves as a control to evaluate the efficacy and safety of Renaparin in improving kidney graft function in recipients of deceased-donor transplants.
Efficacy
The efficacy of Renaparin in improving kidney graft function in deceased-donor transplant recipients will be assessed through a series of primary and secondary endpoints. The primary endpoint is the estimated **glomerular filtration rate (eGFR)** at Month 3, calculated using the MDRD 4 equation. This measurement will provide a quantitative assessment of kidney function post-transplantation.
Secondary endpoints include a variety of parameters to further evaluate renal function and transplant success. These include the incidence of delayed graft function (DGF), defined as the need for dialysis during the first 7 days post-transplantation, and serum creatinine levels measured on Days 1-7, Day 30, and Months 3, 6, and 12. Additionally, eGFR will be assessed on Days 1-7, Day 30, Month 6, and Month 12. The severity of DGF will be determined by the total number of dialysis sessions required by a patient through Day 30, and the incidence of functional DGF will be noted if there is a failure of serum creatinine to decrease by at least 10% daily on 3 consecutive days during the first 7 days post-transplantation.
Other secondary endpoints include the duration of DGF, the proportion of patients with immediate graft function (IGF), and the proportion of patients with primary non-function (PNF). The time to first dialysis, excluding patients with PNF, and urine output on Days 1-3 will also be recorded. These endpoints will be measured and collected at specified timepoints throughout the study to provide a comprehensive evaluation of Renaparin's efficacy in this patient population.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Organs: A kidney must fulfil the following criteria in order to be used in the study: 1) Kidney must come from a deceased donor at least 18 years of age. 2) Kidneys donated after brain death (DBD-ECD) or kidneys donated after circulatory death (DCD).
- Patients: A patient must fulfil the following criteria in order to be included in the study: 3) Male or female patient 18 – 75 years of age. 4) Dialysis-dependent (initiated more than two months prior to transplantation) patient, acceptable candidate for kidney transplantation. 5) Female patients must be post-menopausal, surgically sterile or using effective methods of contraception during study treatment (3 months)*. Acceptable birth control methods are those with a failure rate of less than 1% per year when used consistently and correctly. Such methods include: a) Combined (oestrogen and progestogen containing hormonal contraception associated with inhibition of ovulation -oral -intravaginal -transdermal b) progestogen-only hormonal contraception associated with inhibition of ovulation -oral -injectable -implantable c) intrauterine device d) intrauterine hormone-releasing system e) bilateral tubal occlusion f) vasectomized partner 6) Patient weight 45-115 kg. 7) Negative crossmatch test prior to transplantation and no evidence of donor-specific antibodies. 8) Patients able to give informed consent to participate in study.*Note: As per the Clinical Trial Facilitation Group (CTFG), the definition of woman of childbearing potential is as follows: fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy (HRT). However, in the absence of 12 months of amenorrhea, confirmation with more than one FSH measurement is required.
Exclusion Criteria
- Organs: The presence of any of the following will exclude a kidney from being used in the study: 1) Kidney judged by the transplantation surgeon on call as not appropriate for transplantation. 2) Kidney allograft that was on HMP > 6 hrs prior to administration of IMP, or prior to transplantation for the control kidney. 3) Kidney judged to need preservation by HMP up until transplantation.
- Patients: The presence of any of the following will exclude a patient from participating in the study: 4) Increased risk of thrombosis (e.g., homozygous activated protein C [APC]-resistance) or bleeding (INR>1.5). 5) History of heparin-induced thrombocytopenia (HIT). 6) Known fish allergy. 7) History of or positive for human immunodeficiency virus (HIV). 8) Acute infection with hepatitis B virus (HBV), or hepatitis C virus (HCV). 9) History of oncological malignancy within the last five years, except excised squamous or basal cell carcinoma of the skin. 10) Previous kidney transplantation. 11) Scheduled to undergo multi-organ transplantation or dual kidney transplantation. 12) Positive T or B cell crossmatch by NIH anti-globulin lymphocytotoxicity method or positive T or B cell flow cytometry crossmatch AND donor specific anti-HLA antibody (DSA) detected by flow cytometry/Luminex based, antigen specific anti-HLA antibody testing, according to local practise. 13) Current drug and/or alcohol abuse. 14) History or presence of a medical condition or disease or psychiatric condition that in the investigator's assessment would place the patient at an unacceptable risk for study participation. 15) Lactating or pregnant women or women who intend to become pregnant. 16) Presence of ECG-based evidence of acute myocardial infarction, unstable angina, decompensated heart failure, third degree of heart block or cardiac arrhythmia associated with haemodynamic stability. 17) Any medical condition which in the opinion of the investigator makes the patient unsuitable for inclusion. 18) Enrolment in another concurrent clinical interventional study, or intake of an IMP, within 3 months prior to inclusion in this study. 19) Foreseeable inability to cooperate with given instructions or study procedures. 20) Patients receiving prophylactic treatment of lymphocyte-depleting agents (e.g., anti-thymocyte globulin [ATG] or Campath). 21) Hypersensitivity to the IMP or to any of the excipients, or previous hypersensitivity to heparin as well as any contraindication for heparin.* *Note: Contraindication includes (but not limited to – depending on the investigator’s decision): - Current or history of allergic thrombocytopenia to heparin (heparin-associated thrombocytopenia type II) - Active major bleeding and risk factors for major bleeding - Septic endocarditis - Spinal anesthesia, epidural anesthesia, lumbar puncture - Diseases where there is a suspicion of a lesion of the vascular system, e.g. Gastric and/or intestinal ulcers, consistent hypertension (greater than 110 mmHg diastolic), cerebral hemorrhage, trauma or central nervous system surgery, eye surgery, retinopathy, vitreous hemorrhage, cerebral artery aneurysm.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Austria | Not Yet Recruiting | 31 Aug 2026 | 22 |
 Germany | Not Yet Recruiting | 31 Aug 2026 | 30 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Renaparin | Test | SOLUTION FOR ORGAN PRESERVATION | EXTERNAL USE | 100 | 1 | PRD9856683 |