H-Guard Pilot Safety Evaluation in Haemodialysis Patients

This prospective, open-label, study will be conducted in accordance with the requirements of EN ISO 14155, the Declaration of Helsinki (revised version of Edinburgh, Scotland 2000), Good Manufacturing Practice (GMP), Good Clinical Practice (GCP) and the current national regulations and guidelines, approved by both the local ethics committee and regulatory authority.

The study will be performed in a stable participant population who are on haemodialysis and who have a blood biomarker profile at screening, suggesting an increased risk of sensitivity to the haemodialysis dialyser and/or blood tubing sets (C3 deposition assay ratio ≤0.3 - measured immunologically using a C3 antibody in H-Guard vs human serum albumin coated ELISA plates). Participants will be recruited based on participation in a prior screening study and will attend a total of six-seven consecutive visits during the clinical trial

• Screening [up to 30 days prior to the start of the clinical trial]
• A non-interventional haemodialysis using standard priming solutions [Baseline - mid-week session: Day 0]
• For WoCBP - a serum hCG test will be repeated between days 1-6 prior to intervention
• A single haemodialysis using H-Guard to first prime the dialyser and tubing set [mid-week session: Day 7]
• Followed by a further non-interventional haemodialysis without H-Guard [i.e. using standard priming solutions] [first haemodialysis post intervention]
• A follow up visit 7 days post intervention to perform antibody analysis
• Finally a follow up visit 14-21 days post intervention to perform antibody analysis.

Inclusion criteria

• Male or female subjects aged 18 years and older at screening who have provided a signed and dated written informed consent
• Stable haemodialysis patients who are undergoing centre-based maintenance haemodialysis due to advanced kidney disease CKD stage 5, via arterio-venous fistula, graft or central venous catheter (i.e. with or without permanent vascular access)
• C3 deposition assay ratio ≤0.3 - measured immunologically using a C3 antibody in H-Guard vs human serum albumin coated ELISA plates
• Cytokine release assay - IL-6 concentrations following H-Guard vs Human Serum Albumin exposure must not exceed >50% and absence of significant Human Serum Albumin stimulated reactivity
• Willing and able to attend and comply with study visits and study related activities

Exclusion criteria

• Patients requiring haemodialysis for acute kidney injury on critical care (ITU)
• Patients unable or unwilling to comply with all trial procedures, e.g. blood sampling
• Patients with a likely survival prognosis of less than 6 months
• Patients who have been admitted for any acute hospital-based treatments in the last 6 weeks
• Patients on any medication which may interfere with the analysis of the biomarkers
• Current or history of use of anti-thrombotic therapy less than 7 days prior to screening.
• Currently active malignancy
• Currently receiving radiation, immunotherapy or chemotherapy
• Patients with active infection or receiving antibiotics within 30 days prior to screening
• Currently enrolled or has been enrolled in the last 30 days in another investigational device or drug study
• Known allergy or hypersensitivity to any component of the study device and/or medication to be used during the study.
• Patients lacking capacity to provide informed consent
• Pregnant or breastfeeding women
• Women of child-bearing potential (WoCBP)* who are unwilling to practice highly effective contraception** or undergo pregnancy tests at screening and during the study***
• Positive HIV and hepatitis B and C status, assessed from medical records only
• Patients with haematology or biochemistry results out of the normal reference range for this indication, assessed from medical records using test results obtained within 30 days of screening visit Any patients who are not deemed suitable for the study, as per the investigator's clinical opinion.

• Pregnancy testing and contraception are not required for women not of child-bearing potential, including postmenopausal women or those with documented hysterectomy or bilateral oophorectomy. Postmenopausal women must be amenorrhoeic for at least 12 months in order not to be considered of childbearing potential. When postmenopausal status is uncertain, this will be confirmed by measurement of FSH.

• Highly effective contraceptive measures include stable use of combined (oestrogen and progestogen containing) hormonal contraception (oral, intravaginal, transdermal) or progestogen-only hormonal contraception (oral, injectable, implantable) associated with inhibition of ovulation initiated 2 or more menstrual cycles prior to screening; intrauterine device (IUD); intrauterine hormone-releasing system (IUS); bilateral tubal ligation; vasectomized partner; and sexual abstinence***.

• Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical study and the preferred and usual lifestyle of the patient.