A Study of Safety, PK, & PD of ISIS 416858 Administered Subcutaneously to Patients With End-Stage Renal Disease on Hemodialysis

Ionis Pharmaceuticals

Status and phase: Completed; Phase 2

Conditions: End-stage Renal Disease (ESRD)

Treatments: Drug: ISIS 416858; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT02553889

ISIS 416858 CS4

Details and patient eligibility

About

Evaluation of safety, tolerability, PK and PD of ISIS 416858 in patients with end-stage renal disease (ESRD) receiving chronic hemodialysis.

Full description

Evaluation of Safety, PK and PD of ISIS 416858 in patients with end-stage renal disease (ESRD) receiving chronic hemodialysis.

The overall objectives are to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of ISIS 416858 in ESRD patients on hemodialysis.

Enrollment: 49 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• End stage renal disease maintained on outpatient hemodialysis at a healthcare center for > 3 months from screening with hemodialysis using heparin (unfractionated heparin or low-molecular weight heparin) 3 times per week for a minimum of 3 hours per dialysis session and plan to continue this throughout the study.

Exclusion criteria

• Documented thrombotic event (acute coronary syndrome, stroke or transient ischemic attack, venous thromboembolic event) in the past 3 months.

• Active bleeding within the past 3 months from screening or documented bleeding diathesis (history of bleeding disorder) or Screening values of:

  • Platelet count < 150,000 cells/mm3
  • INR > 1.4
  • aPTT > upper limit of normal (ULN)

• Abnormal liver function at Screening:

  • ALT or AST > 2 x ULN
  • Total bilirubin > ULN

• Concomitant medication restrictions: Concomitant use of anticoagulant/antiplatelet agents (e.g., dabigatran, rivaroxaban, clopidogrel) that may affect coagulation (except low dose aspirin (≤ 100 mg/day) during Treatment and Post-treatment Evaluation Periods is not allowed.

• Uncontrolled hypertension as judged by the Investigator. Patients with a pre- or post-dialysis blood pressure (BP) that is > 160 mmHg on at least 3 of last 5 dialysis treatments.

• Planned major surgery in the next 6 months (e.g. renal transplant surgery)

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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49 participants in 3 patient groups, including a placebo group

PK Cohort

Experimental group

Description:

A 4-week screening period followed by a 4-week treatment period followed by a 6-week post-treatment evaluation period. Treatment period includes 1 dose of 300 mg ISIS 416858 on Day 1 and again on Day 29. Both doses of Study Drug will be administered subcutaneously (SC).

Treatment:

Drug: ISIS 416858

Cohort A

Placebo Comparator group

Description:

Patients in Cohort A will be randomized to receive either 200 mg ISIS 416858 or placebo. A 2:1 ratio will be used. For Cohort A, the study will include a 4-week screening period and a 12-week treatment period followed by a 12-week post-treatment evaluation period. Cohort A will receive Study Drug (ISIS 416858 or placebo) twice a week during the first 2 weeks, followed by once weekly for the remaining 10 weeks of the treatment period. All doses of Study Drug will be administered subcutaneously (SC) 10 minutes after completion of the hemodialysis treatment.

Treatment:

Drug: Placebo

Drug: ISIS 416858

Cohort B

Placebo Comparator group

Description:

Patients in Cohort B will be randomized to receive either 300 mg ISIS 416858 or placebo. A 2:1 ratio will be used. For Cohort B, the study will include a 4-week screening period and a 12-week treatment period followed by a 12-week post-treatment evaluation period. Cohort B will receive Study Drug (ISIS 416858 or placebo) twice a week during the first 2 weeks, followed by once weekly for the remaining 10 weeks of the treatment period. All doses of Study Drug will be administered subcutaneously (SC) 10 minutes after completion of the hemodialysis treatment.

Treatment:

Drug: Placebo

Drug: ISIS 416858