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Completed

NCT Number: NCT02553889

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

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

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Key information

Conditions

End-stage Renal Disease (ESRD) Chronic Disease Disease Attributes Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Kidney Diseases Kidney Failure, Chronic Male Urogenital Diseases Pathologic Processes Pathological Conditions, Signs and Symptoms Renal Insufficiency Renal Insufficiency, Chronic Urogenital Diseases Urologic Diseases

Age range

18 year–80 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Ionis Investigative Site, Edmonton, Alberta, Canada

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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)

Treatment and study plan

ISIS 416858

Drug

subcutaneous injection

Other names: ISIS-FXI Rx, BAY2306001, IONIS-FXI Rx

Placebo

Drug

subcutaneous injection

Other names: 0.9% sterile saline

Primary outcomes

  1. Safety and Tolerability - evaluated by reviewing frequency and severity of Adverse events (including bleeding events) and use of concomitant medications, changes in vital signs and laboratory evaluations for all patients

    Time frame: For the PK Cohort: Patients will be followed for 72 days. For Cohorts A and B: Patients will be followed for 162 days.

    The safety and tolerability of ISIS 416858 will be evaluated by reviewing frequency and severity of Adverse events (including bleeding events) and use of concomitant medications, changes in vital signs and laboratory evaluations for all patients

Secondary outcomes

  1. Pharmacodynamic Outcomes in FXI antigen and activity as measured by absolute change over time.

    Time frame: For the PK Cohort: Patients will be followed for 72 days. For Cohorts A and B: Patients will be followed for 162 days.

    Pharmacodynamic Outcomes as measured by absolute change over time for FXI antigen and activity (units/milliliter)

  2. Pharmacodynamic Outcomes in FXI antigen and activity as measured by percent change over time.

    Time frame: For the PK Cohort: Patients will be followed for 72 days. For Cohorts A and B: Patients will be followed for 162 days.

    Pharmacodynamic Outcomes as measured by percent change over time for FXI antigen and activity (units/milliliter)

  3. Pharmacodynamic Outcomes in aPTT as measured by absolute change over time.

    Time frame: For the PK Cohort: Patients will be followed for 72 days. For Cohorts A and B: Patients will be followed for 162 days.

    Pharmacodynamic Outcomes as measured by absolute change over time for aPTT (seconds)

  4. Pharmacodynamic Outcomes in aPTT as measured by percent change over time.

    Time frame: For the PK Cohort: Patients will be followed for 72 days. For Cohorts A and B: Patients will be followed for 162 days.

    Pharmacodynamic Outcomes as measured by percent change over time for aPTT (seconds)

  5. Pharmacodynamic Outcomes for PT and the PT derived INR as measured by absolute change over time.

    Time frame: For the PK Cohort: Patients will be followed for 72 days. For Cohorts A and B: Patients will be followed for 162 days.

    Pharmacodynamic Outcomes as measured by absolute change over time for PT (seconds) and the PT derived INR (International Normalization Ratio)

  6. Pharmacodynamic Outcomes for PT and the PT derived INR as measured by percent change over time.

    Time frame: For the PK Cohort: Patients will be followed for 72 days. For Cohorts A and B: Patients will be followed for 162 days.

    Pharmacodynamic Outcomes as measured by percent change over time for PT (seconds) and the PT derived INR (International Normalization Ratio)

Other outcomes

  1. Pharmacokinetic Outcome for PK Cohort of effect of dialysis on peak concentrations

    Time frame: Patients will be followed for 29 days for this outcome measure.

    Effect of dialysis on peak concentrations post single dose drug administration.

  2. Pharmacokinetic Outcome for PK Cohort of effect of dialysis on partial area under the plasma concentration-time curve

    Time frame: Patients will be followed for 29 days for this outcome measure.

    Effect of dialysis on partial area under the plasma concentration-time curve post single dose drug administration (AUC 0-24hr).

  3. Pharmacokinetic Outcome for Cohorts A and B to assess steady state concentrations

    Time frame: Patients will be followed for 162 days for this outcome measure

    Plasma will be collected at each dosing interval to assess steady state concentrations.

Sponsors and collaborators

Lead sponsor

Ionis Pharmaceuticals, Inc.

Industry

Collaborators

  • Bayer

Registry information

Official study title

A Phase 2, Randomized, Double Blind, Placebo Controlled Study of the Safety, PK, and PD of Multiple Doses of ISIS 416858 (ISIS-FXI RX), Administered Subcutaneously to Patients With End-Stage Renal Disease on Hemodialysis

Important dates

Study start
2015
Primary completion
2016
Study completion
2016
First posted
Sep 18, 2015
Registry last updated
Dec 13, 2016

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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