Safety of Anakinra in Pancreatic Transplant Recipients to Prevent Immunothrombosis in Combination Therapy with Tacrolimus, Mycophenolic Acid, and Etanercept

The primary objective of this study is to evaluate the safety of anakinra in a pilot series of patients undergoing pancreatic transplantation. Secondary objectives include:

• Assessment of one-year patient survival and pancreatic graft survival post-transplantation.
• Evaluation of pancreatic graft function and, in cases of simultaneous kidney-pancreas transplantation, renal graft function.
• Monitoring the incidence of pancreatic graft rejection and renal graft rejection.
• Detection of graft-directed antibodies.
• Assessment of infectious complications, specifically bacterial infections, CMV infection, BK virus infection, and fungal infection.

The sponsor did not provide information regarding the total number of participants. The study population consists of individuals undergoing pancreatic transplantation, either as a solitary procedure or in combination with a kidney transplant. Eligible participants include adults aged 18 years or older, encompassing both male and female subjects. Inclusion is limited to patients with a transplant priority level of 1, 2, or 3 who are affiliated with the social security system. Necessary requirements for participation include the provision of written consent, the use of contraceptive measures, and a negative pregnancy test.

This integrated Phase I/II clinical trial aims to evaluate the safety of anakinra in recipients of a pancreatic transplant. The study methodology involves a pilot series of patients undergoing either isolated pancreatic transplantation or simultaneous kidney-pancreas transplantation. Participants receiving the test product may also be treated with auxiliary medications including tacrolimus, mycophenolic acid, and etanercept. The primary objective is to monitor the type, severity, and frequency of adverse events during the first year following transplantation, specifically focusing on graft survival, rejection confirmed by biopsy, and severe infections. Secondary endpoints include the assessment of patient survival, pancreatic graft failure, glycemic control via C-peptide and HbA1c levels, and renal function parameters such as creatinine and estimated glomerular filtration rate. The study period is expected to occur between April 2026 and October 2028, with participant involvement extending for one year post-transplantation to allow for the evaluation of clinical outcomes and complications such as CMV viraemia or BK virus infections.

The experimental treatment consists of anakinra, provided as a 100 mg/0.67 ml solution for injection in a pre-filled syringe. This substance is administered via subcutaneous injection.

Background therapies include etanercept, administered as a 25 mg solution for injection via a subcutaneous route. Mycophenolic acid is utilized in the form of 360 mg gastro-resistant tablets for oral administration. Additionally, tacrolimus is provided as 1 mg hard capsules for oral use.

The primary efficacy evaluation focuses on the type, severity, and frequency of adverse events occurring within the first year following pancreatic transplantation. Specific attention is directed toward the incidence of severe infections, including bacterial, viral, fungal, or parasitic infections that are life-threatening or necessitate hospitalization. Additionally, the assessment includes the occurrence of rejection confirmed via biopsy and graft survival relative to a historical control cohort.

Secondary endpoints measured one year after transplantation include:

• Patient survival, defined by the patient being alive at the one-year mark.
• Pancreatic graft failure, determined by the requirement for daily insulin, pancreas transplantectomy, pancreatic retransplantation, or islet cell transplantation.
• Metabolic parameters, including C-peptide, fasting blood glucose, insulin requirements, and HbA1c, utilized to calculate the β2 score and Igls criteria, alongside an oral glucose tolerance test.
• Renal function markers, such as creatinine levels, estimated glomerular filtration rate calculated via the CKD-EPI formula, and proteinuria in cases of simultaneous kidney-pancreas transplantation.
• Incidence of CMV viraemia and BK virus viremia, including cases associated with organ damage or BK virus nephropathy confirmed by biopsy.
• Occurrence of proven fungal infection.
• Pancreatic rejection, identified through pancreatic biopsy according to Banff criteria or renal biopsy in the presence of associated clinical markers such as elevated lipasaemia, unexplained inflammatory syndrome, or unexplained hyperglycaemia.
• Renal graft rejection confirmed by renal biopsy according to Banff criteria.
• Presence of graft-directed antibodies at one year, defined by a Mean Fluorescence Index greater than 500.