Effect of SNF472 on Progression of Cardiovascular Calcification in End-Stage-Renal-Disease (ESRD) Patients on Hemodialysis (HD)
Condition: Cardiovascular Diseases; Cardiovascular Abnormalities; Calcifications, Vascular; Endstage Renal Disease; ESRD; Coronary Artery Calcification
MeSH terms: Kidney Diseases; Kidney Failure, Chronic; Cardiovascular Diseases; Cardiovascular Abnormalities; Calcinosis; Vascular Calcification
Intervention: SNF472; Placebo
Intervention description: Administered 3 times weekly by intravenous infusion through the dialysis machine in conjunction with the patient's dialysis sessions.; Administered 3 times weekly by intravenous infusion through the dialysis machine in conjunction with the patient's dialysis sessions.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 274.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: No
Keywords: CAC; calcium; ESRD; calcification; cardiovascular; heart; kidney; hemodialysis; Agatston

Summary:

      The primary objective is to assess the effect of 2 dose levels of SNF472 (300 mg and 600 mg)
      compared to placebo on the progression of coronary artery calcium volume score over a
      12-month (52 weeks) period in ESRD patients on HD
    

Eligibility criteria:

        Inclusion Criteria:

          -  Female or male patients, 18 to 80 years (inclusive) of age at randomisation

          -  CAC score of 100 to 3500 AU (Agatston Units) inclusive within a 3-week period prior to
             randomisation as measured by a multi-detector CT scanner

          -  Patients who are EITHER ≥ 55 years OR have a history of diabetes mellitus at
             randomisation

          -  Patients on HD for ≥ 6 months prior to randomisation

          -  Willing and able to understand and sign the informed consent

        Exclusion Criteria:

          -  Scheduled date for kidney transplant from a known living donor

          -  Weight above 300 lbs (136 kg)

          -  Hospitalisation in the previous 3 months prior to randomisation for unstable angina,
             MI, stroke, transient ischaemic attack, amputation or peripheral or coronary bypass
             surgery

          -  History of unstable heart failure in the previous 3 months, defined as an unplanned
             presentation to a hospital or dialysis treatment facility with signs/symptoms of acute
             pulmonary edema and requiring ultrafiltration therapy

          -  History of cancer that has been in remission for < 5 years prior to randomisation. A
             history of basal cell carcinoma or Stage 1 squamous cell carcinoma of the skin is
             allowed

          -  Pregnant or trying to become pregnant, currently breast-feeding, or of child-bearing
             potential (including peri-menopausal women who have had a menstrual period within one
             year) and not willing to practice birth control using a double barrier method
             (criteria apply to women only) at least 30 days post last dose of study medication

          -  Hypocalcaemia defined as a serum calcium below 8.0 mg/dL (or 2.0 mmol/L) for the serum
             calcium most proximal to screening per patient's medical records

          -  Extreme elevation in serum phosphorous, defined as a serum phosphorous above 10 mg/dL
             (or 3.23 mmol/L) within the last 2 months proximal to screening per patient's medical
             records

          -  Uncontrolled hypertension defined as any 2 or more consecutive post-dialysis diastolic
             blood pressure (DBP) > 100 mmHg within the last 2 months proximal to screening
             expected survival < 2 years in the Investigator's medical opinion

          -  Known active drug or alcohol abuse within 1 year of randomisation

          -  Use of other investigational drugs within 30 days of randomisation

          -  Non-compliance with dialysis treatment which, in the opinion of the Investigator,
             evidenced by either repeated missed dialysis treatments or significant non-compliance
             with the patient's medication regimen

          -  Inability to comply with all required study procedures and schedule, inability to
             speak and read in the protocol-derived language of that patient's clinical site, or
             unwillingness or inability to give written informed consent