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

End-stage Renal Disease (ESRD) Clinical Trial

Official 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02553889
• Other study ID #: ISIS 416858 CS4
• Status: Completed
• Phase: Phase 2
• First received: September 14, 2015
• Last updated: December 12, 2016
• Start date: October 2015
• Est. completion date: November 2016

Study information

• Verified date: December 2016
• Source: Ionis Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Health Canada
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 49
• Est. completion date: November 2016
• Est. primary completion date: November 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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)

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• End-stage Renal Disease (ESRD)
• Kidney Diseases
• Kidney Failure, Chronic
• Renal Insufficiency, Chronic

Intervention

Drug:
• ISIS 416858
subcutaneous injection
• Placebo
subcutaneous injection

Locations

Country	Name	City	State
Canada	Ionis Investigative Site	Edmonton	Alberta
Canada	Ionis Investigative Site	Halifax	Nova Scotia
Canada	Ionis Investigative Site	Hamilton	Ontario
Canada	Ionis Investigative Site	London	Ontario
Canada	Ionis Investigative Site	Montreal	Quebec
Canada	Ionis Investigative Site	Montreal	Quebec
Canada	Ionis Investigative Site	Toronto	Ontario
Canada	Ionis Investigative Site	Toronto	Ontario

Sponsors (2)

Lead Sponsor	Collaborator
Ionis Pharmaceuticals, Inc.	Bayer

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Pharmacokinetic Outcome for PK Cohort of effect of dialysis on peak concentrations	Effect of dialysis on peak concentrations post single dose drug administration.	Patients will be followed for 29 days for this outcome measure.	No
Other	Pharmacokinetic Outcome for PK Cohort of effect of dialysis on partial area under the plasma concentration-time curve	Effect of dialysis on partial area under the plasma concentration-time curve post single dose drug administration (AUC 0-24hr).	Patients will be followed for 29 days for this outcome measure.	No
Other	Pharmacokinetic Outcome for Cohorts A and B to assess steady state concentrations	Plasma will be collected at each dosing interval to assess steady state concentrations.	Patients will be followed for 162 days for this outcome measure	No
Primary	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	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	For the PK Cohort: Patients will be followed for 72 days. For Cohorts A and B: Patients will be followed for 162 days.	Yes
Secondary	Pharmacodynamic Outcomes in FXI antigen and activity as measured by absolute change over time.	Pharmacodynamic Outcomes as measured by absolute change over time for FXI antigen and activity (units/milliliter)	For the PK Cohort: Patients will be followed for 72 days. For Cohorts A and B: Patients will be followed for 162 days.	No
Secondary	Pharmacodynamic Outcomes in FXI antigen and activity as measured by percent change over time.	Pharmacodynamic Outcomes as measured by percent change over time for FXI antigen and activity (units/milliliter)	For the PK Cohort: Patients will be followed for 72 days. For Cohorts A and B: Patients will be followed for 162 days.	No
Secondary	Pharmacodynamic Outcomes in aPTT as measured by absolute change over time.	Pharmacodynamic Outcomes as measured by absolute change over time for aPTT (seconds)	For the PK Cohort: Patients will be followed for 72 days. For Cohorts A and B: Patients will be followed for 162 days.	No
Secondary	Pharmacodynamic Outcomes in aPTT as measured by percent change over time.	Pharmacodynamic Outcomes as measured by percent change over time for aPTT (seconds)	For the PK Cohort: Patients will be followed for 72 days. For Cohorts A and B: Patients will be followed for 162 days.	No
Secondary	Pharmacodynamic Outcomes for PT and the PT derived INR as measured by absolute change over time.	Pharmacodynamic Outcomes as measured by absolute change over time for PT (seconds) and the PT derived INR (International Normalization Ratio)	For the PK Cohort: Patients will be followed for 72 days. For Cohorts A and B: Patients will be followed for 162 days.	No
Secondary	Pharmacodynamic Outcomes for PT and the PT derived INR as measured by percent change over time.	Pharmacodynamic Outcomes as measured by percent change over time for PT (seconds) and the PT derived INR (International Normalization Ratio)	For the PK Cohort: Patients will be followed for 72 days. For Cohorts A and B: Patients will be followed for 162 days.	No