TY - JOUR
T1 - Multicentre, multi-arm, double-blind randomised placebo-controlled dose-finding trial investigating the safety and Efficacy of MirococePt (APT070) In Reducing delayed graft function In the Kidney ALlograft (EMPIRIKAL-2)
T2 - study protocol for a randomised controlled trial
AU - Kassimatis, Theodoros
AU - Rahman, Alima
AU - Jaradat, Fayyad
AU - Douiri, Abdel
AU - Delord, Marc
AU - Greenlaw, Roseanna
AU - Palmer Joyce, Joanne
AU - Olsburgh, Jonathon
AU - Khurram, Muhammad
AU - Ghazanfar, Abbas
AU - Knight, Simon
AU - Friend, Peter
AU - Shah, Sapna
AU - Killbride, Hannah
AU - Smith, Richard
AU - Sacks, Steven
N1 - © Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY. Published by BMJ Group.
Publisher Copyright:
© Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY. Published by BMJ Group.
PY - 2025/3/6
Y1 - 2025/3/6
N2 - Background Up to 50% of kidney transplant patients are diagnosed with delayed graft function (DGF) following transplantation - the majority being linked to ischaemia reperfusion injury (IRI). DGF is traditionally defined as the requirement for dialysis during the first week after transplantation and is associated with inferior graft and patient outcomes. Local synthesis of complement components, largely by the renal tubule, plays a critical role in IRI. We have developed Mirococept, a membrane-targeted complement inhibitor, that can be administered to the donor kidney ex vivo prior to transplantation. After administration, Mirococept is retained in the donor organ, thereby minimising the risk of systemic side effects. We previously launched the EMPIRIKAL study aiming to evaluate the efficacy of Mirococept in reducing DGF in deceased-donor kidney transplantation (KT). The funding body recommended termination of the study to allow a dose-saturating study before the next stage of clinical evaluation. This was carried out in a porcine kidney model and led to a revised dosing regimen for EMPIRIKAL-2 (60-180 mg compared with 5-25 mg in the initial trial). The EMPIRIKAL-2 trial (REC 24/NE/0071) aims to identify the most safe and efficacious dose of Mirococept to reduce DGF rate in deceased-donor KT. Methods and analysis EMPIRIKAL-2 is a Phase IIa multicentre double-blind randomised controlled trial (RCT) with an initial safety run. Participants will be recruited from renal departments at National Health Service tertiary hospital sites in the UK. The purpose of the safety run is to assess the tolerance of each of the three proposed Mirococept doses (60, 120 or 180 mg), before the RCT begins. Three patients will be assigned to each treatment dose, starting from the lower dose. The safety run will be considered successful if at least one dose can be taken forward to the RCT for comparison to placebo. If safety is met, 144 participants (36 per arm excluding drop-outs) will be randomised to all doses meeting the safety criteria or placebo on a 1:1:1:1 basis. The primary endpoint is DGF, defined as the requirement for dialysis during the first week after transplantation. Safety evaluation will include the monitoring of laboratory data and the recording of all adverse events. Immunosuppression therapy, antibiotic and antiviral prophylaxis will be administered as per local centre protocols. Enrolment in the RCT is anticipated to take approximately 12 months, and patients will be followed-up for 12 months. Ethics and dissemination The study has been approved by the Northeast - Newcastle and North Tyneside 2 Research Ethics Service Committee, REC reference 24/NE/0071. The results of the study will be reported and disseminated at international conferences and in peer-reviewed scientific journals. Once published, a lay summary of the results will be made available to participants who request this information.
AB - Background Up to 50% of kidney transplant patients are diagnosed with delayed graft function (DGF) following transplantation - the majority being linked to ischaemia reperfusion injury (IRI). DGF is traditionally defined as the requirement for dialysis during the first week after transplantation and is associated with inferior graft and patient outcomes. Local synthesis of complement components, largely by the renal tubule, plays a critical role in IRI. We have developed Mirococept, a membrane-targeted complement inhibitor, that can be administered to the donor kidney ex vivo prior to transplantation. After administration, Mirococept is retained in the donor organ, thereby minimising the risk of systemic side effects. We previously launched the EMPIRIKAL study aiming to evaluate the efficacy of Mirococept in reducing DGF in deceased-donor kidney transplantation (KT). The funding body recommended termination of the study to allow a dose-saturating study before the next stage of clinical evaluation. This was carried out in a porcine kidney model and led to a revised dosing regimen for EMPIRIKAL-2 (60-180 mg compared with 5-25 mg in the initial trial). The EMPIRIKAL-2 trial (REC 24/NE/0071) aims to identify the most safe and efficacious dose of Mirococept to reduce DGF rate in deceased-donor KT. Methods and analysis EMPIRIKAL-2 is a Phase IIa multicentre double-blind randomised controlled trial (RCT) with an initial safety run. Participants will be recruited from renal departments at National Health Service tertiary hospital sites in the UK. The purpose of the safety run is to assess the tolerance of each of the three proposed Mirococept doses (60, 120 or 180 mg), before the RCT begins. Three patients will be assigned to each treatment dose, starting from the lower dose. The safety run will be considered successful if at least one dose can be taken forward to the RCT for comparison to placebo. If safety is met, 144 participants (36 per arm excluding drop-outs) will be randomised to all doses meeting the safety criteria or placebo on a 1:1:1:1 basis. The primary endpoint is DGF, defined as the requirement for dialysis during the first week after transplantation. Safety evaluation will include the monitoring of laboratory data and the recording of all adverse events. Immunosuppression therapy, antibiotic and antiviral prophylaxis will be administered as per local centre protocols. Enrolment in the RCT is anticipated to take approximately 12 months, and patients will be followed-up for 12 months. Ethics and dissemination The study has been approved by the Northeast - Newcastle and North Tyneside 2 Research Ethics Service Committee, REC reference 24/NE/0071. The results of the study will be reported and disseminated at international conferences and in peer-reviewed scientific journals. Once published, a lay summary of the results will be made available to participants who request this information.
KW - Kidney Transplantation
KW - Humans
KW - Delayed Graft Function/prevention & control
KW - Double-Blind Method
KW - Randomized Controlled Trials as Topic
KW - Multicenter Studies as Topic
KW - Animals
KW - Swine
KW - Male
UR - http://www.scopus.com/inward/record.url?scp=86000674451&partnerID=8YFLogxK
U2 - 10.1136/bmjopen-2024-097029
DO - 10.1136/bmjopen-2024-097029
M3 - Article
C2 - 40050053
SN - 2044-6055
VL - 15
JO - BMJ Open
JF - BMJ Open
IS - 3
M1 - e097029
ER -