A Phase I clinical study of AntiPlatelet, AntiCoagulant (APAC) in chronic kidney disease patients to facilitate hemodialysis access.

Recruitment & Eligibility

Status: Open to Recruitment

Sex: Not specified

Target Recruitment: 0

Inclusion Criteria

1.Dialysis naïve patients with CKD stages 4 and 5 (defined as an eGFR less than 30 mL/min/1.73m2), =18 and <65 years of age of either gender, requiring

hemodialysis access surgery.

2.Patient eligible to undergo AVF surgery as determined by the nephrologist and surgeon.

3.Patients with appropriate vessel diameters: a radial artery and a cephalic vein diameter = 2 mm (inner-to-inner diameter), measured via duplex ultrasound.

4.Venous patency in the draining vein with no stenosis or thrombosis, with

visible, palpable, and compressible (thrombus free) vein.

5.Life expectancy of at least 12 months and not likely to require kidney transplantation within 3 months of administration of study medication.

6.Patients able to provide written informed consent and willing to follow all study requirements.

Exclusion Criteria

1.Patients already receiving hemodialysis or who have previously undergone dialysis, successful or otherwise.

2.Existing AVF at any anatomical site.

3.Patients in whom the intended site for surgical intervention is the only potential site for an AVF.

4.Patients taking a contraindicated medication which will interfere with the study outcome.

5.Patients receiving warfarin, unfractionated heparin, LMWH or any other systemic anticoagulant, such as direct oral anticoagulants at Screening

6.Patients who are taking or who have taken antiplatelet agents during 30 days prior to Screening, excluding aspirin.

7.Patients with a history of known sensitivity to heparin or aspirin.

8.Patients with APTT i.e., =1.5-fold prolongation, PT >1.5 of ULN, LFT >2.5 of ULN, Hb <7 g/dL

9.Patients with a history of myocardial infarction, stroke, peripheral arterial occlusive disease, angioplasty, previous venous thromboembolism, transient ischemic attack (TIA).

10.Patients with known medical history of nephrotic syndrome, arterial aneurysm, heparin-induced thrombocytopenia, inherited or acquired thrombophilic condition or symptoms of fever or active infection or any other medical condition or underlying cause for their CKD.

11.Patients demonstrating an absence of radial and/or ulnar arterial blood flow or non-patent palmer arch, as determined via a modified Allen test at Screening.

12.Patients with any systemic condition (as noted in their medical history at Screening) known to be associated with impaired hemostasis e.g., hemophilia, Von Willebrand’s disease or other bleeding disorders.

13.Concurrent involvement in any other clinical study with an investigational drug or device, or participation in a clinical study within 30 days prior to entering the study.

14.Female patients who are pregnant, lactating or of childbearing potential and unwilling or unable to use adequate contraception

15.Patients who for any reason, in the investigator’s opinion, are unsuitable for enrolment into the study.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Determination of the highest safe dose by evaluating the safety and tolerability of of APAC during AVF creation in patients with CKDTimepoint: During the first 24-hours post-the AVF surgery and administration of APAC

Secondary Outcome Measures

Name	Time	Method
Determination of AVF maturation rate, functional AVF patency rate and AVF failure rateTimepoint: At Week 4 following surgery;To determine a Recommended Phase 2 Dose(s) (RP2D)Timepoint: During 4 weeks post-surgery and treatment;To establish the safety and tolerability profile of APACTimepoint: During the 4 weeks post-surgery and treatment