A 3-month, phase 2, single-blind, randomised, no-treatment controlled study assessing efficacy and safety of Renaparin® for improvement of kidney graft function in deceased-donor transplant recipients, with an additional 9-month follow-up.

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 meeting 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.

The clinical trial involves a total of **35 participants** who are being studied to assess the effect of Renaparin on graft function in renal transplant patients at high risk of ischemia-reperfusion injury and delayed graft function. The study population includes both **male and female** patients aged between **18 and 75 years**. Participants are required to be dialysis-dependent, having initiated dialysis more than two months prior to transplantation, and must be acceptable candidates for kidney transplantation. The trial population was selected based on specific criteria, including the requirement for female participants to be post-menopausal, surgically sterile, or using effective contraception methods during the study treatment. Participants must weigh between **45 and 115 kg** and have a negative crossmatch test prior to transplantation with no evidence of donor-specific antibodies. The study does not include a vulnerable population, and all participants must be able to provide informed consent. The trial focuses on individuals with **end-stage renal disease** or otherwise insufficient kidney function, and the kidneys used in the study must come from deceased donors meeting specific criteria.

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 the absence of donor-specific antibodies. Eligible participants will then proceed to the baseline visit, where randomization occurs. Study visits will be scheduled at regular intervals, including Days 1-7, Day 30, and Months 3, 6, and 12, to monitor 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.

Participants are expected to be involved in the study for the entire 12-month duration unless conditions arise that necessitate early termination, such as adverse events or withdrawal of consent. The trial's design ensures that all participants are monitored closely to maintain safety and data integrity. The study's rigorous methodology and structured visit schedule aim to provide comprehensive insights into the therapeutic potential of Renaparin in this patient population.

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 and total dose of Renaparin is 100 mg, administered over a treatment period of one day. The solution is applied externally to the organ, ensuring optimal preservation conditions. Renaparin is classified as an orphan drug, indicating its use in rare conditions, and is not formulated for pediatric use.

In addition to the experimental treatment, the study may involve the use of a standard **anticoagulant solution** as a non-experimental treatment. This comparator treatment is utilized to assess the efficacy and safety of Renaparin in improving kidney graft function in deceased-donor transplant recipients. The anticoagulant solution serves as a control to evaluate the potential benefits of the experimental medication. Participant compliance with the dosing schedule is monitored throughout the trial to ensure accurate assessment of the treatment's effects.

Efficacy in this clinical trial 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 in the transplant recipients.

Secondary endpoints include a variety of parameters to further evaluate the efficacy of the treatment. 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 at 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 in those needing dialysis within the first 7 days post-transplantation.

Further secondary endpoints include the incidence of functional DGF (fDGF), defined as the failure of serum creatinine to decrease by at least 10% daily on 3 consecutive days during the first 7 days post-transplantation, excluding creatinine decrements due to dialysis. The duration of DGF will be calculated from the date of kidney transplantation until the last dialysis session in patients who required dialysis within the first 7 days. The proportion of patients with immediate graft function (IGF) will be assessed by the creatinine reduction ratio (CRR) of ≥30% between Day 1 and Day 2 post-transplant, regardless of dialysis sessions within the first 7 days. 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 evaluated.