Anakinra for the Treatment of Postprandial Hypoglycemia in a Patient With Total Gastrectomy and End-Stage Renal Disease (AnPHy-ReD)

The interventional period consists of four treatment blocks, each containing four visits. During each visit, the patient receives either Anakinra (A) or placebo (P) in a double-blinded manner, according to a randomized schedule. The sequence within each block (e.g., A-A-P-P or P-A-A-P) is randomly assigned in advance by an independent scientist, ensuring a balanced and unbiased comparison of treatments throughout the trial.

Study visits take place during the patient's regular dialysis sessions. On each visit, the assigned treatment is administered via the hemodialysis blood circuit over 1 minute during the last 30 minutes of each dialysis session by the dialysis personnel.

Placebo comparator will be 0.9% saline solution. A similar size and type of syringe will be used as for the Anakinra syringe making it difficult to distinguish which treatment of the two the patient is receiving.

The patient will receive 0.9% saline solution intravenously through the haemodialysis circuit 30 minutes before the end of the dialysis session, following the same administration procedure as Anakinra to maintain blinding.

Anakinra (Kineret®; r-metHuIL-1ra, Swedish Orphan Biovitrum AB) is a recombinant, non-glycosylated form of the human interleukin-1 receptor antagonist (IL-1Ra). It is a clear, colourless-to-white solution, provided as a 150mg/mL solution in pre-filled syringes, each containing of 100 mg of Anakinra in 0.67ml.

On the assigned study days, the patient will receive in a double-blind manner 100 mg of Anakinra intravenously through the hemodialysis circuit, administered 30 minutes before the end of the dialysis session.

Prevalence and severity of postprandial hypoglycaemia symptoms during Anakinra treatment compared to placebo, assessed using cumulative data from Continuous Glucose Monitoring from all 48-hour treatment periods.

Post-prandial hypoglycaemia symptoms and their severity will be evaluated by the patient using the Edinburgh Hypoglycemia Symptom Scale (EHSS) and are accompanied by a decrease in blood glucose levels within the postprandial period as evaluated through the CGMS.

The postprandial period is defined as the 3 hours following meal intake. A minimum blood glucose cut-off value is not required for symptom reporting. Each treatment period spans the 48 hours following study-drug administration (Anakinra or Placebo).

Changes following treatment with Anakinra compared to placebo during a Mixed Meal Tolerance Test in the AUC, peak and nadir values, and slopes of:

• Glucose
• Insulin
• c-peptide
• GLP-1
• Glucagon
• Cortisol

Prevalence and severity of postprandial hypoglycaemia symptoms during the whole interventional period compared to the Screening period.

Post-prandial hypoglycaemia symptoms and their severity will be evaluated by the patient using the Edinburgh Hypoglycemia Symptom Scale (EHSS) and are accompanied by a decrease in blood glucose levels within the postprandial period as evaluated through the CGMS.

The postprandial period is defined as the 3 hours following meal intake. A minimum blood glucose cut-off value is not required for symptom reporting.-Each treatment period spans the 48 hours following study-drug administration (Anakinra or Placebo).

Adverse events of interest: AEs of interest include adverse events that can be expected during a treatment with Anakinra.

• Identification of hypersensitivity reaction during the Interventional period.
• Detection of any infection during the interventional period.
• Detection of Neutropenia during the interventional period, defined as absolute neutrophil count <1000/mm³.
• Detection of Thrombocytopenia during the Interventional period, defined as platelet count <100 000/mm³.