Clinical trial NCT02553889: A Study of Safety, PK, & PD of ISIS 416858 Administered Subcutaneously to Patients With End-Stage Renal Disease on Hemodialysis
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: End-stage Renal Disease (ESRD)
Lead sponsor: Ionis Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Bayer
First posted: 2015-09-18
Enrollment: 49
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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

Detailed 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.

Eligibility criteria: 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)

Primary outcomes:
measure: 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
timeFrame: For the PK Cohort: Patients will be followed for 72 days. For Cohorts A and B: Patients will be followed for 162 days.
Secondary outcomes:
measure: Pharmacodynamic Outcomes in FXI antigen and activity as measured by absolute change over time.
timeFrame: For the PK Cohort: Patients will be followed for 72 days. For Cohorts A and B: Patients will be followed for 162 days.
measure: Pharmacodynamic Outcomes in FXI antigen and activity as measured by percent change over time.
timeFrame: For the PK Cohort: Patients will be followed for 72 days. For Cohorts A and B: Patients will be followed for 162 days.
measure: Pharmacodynamic Outcomes in aPTT as measured by absolute change over time.
timeFrame: For the PK Cohort: Patients will be followed for 72 days. For Cohorts A and B: Patients will be followed for 162 days.
measure: Pharmacodynamic Outcomes in aPTT as measured by percent change over time.
timeFrame: For the PK Cohort: Patients will be followed for 72 days. For Cohorts A and B: Patients will be followed for 162 days.
measure: Pharmacodynamic Outcomes for PT and the PT derived INR as measured by absolute change over time.
timeFrame: For the PK Cohort: Patients will be followed for 72 days. For Cohorts A and B: Patients will be followed for 162 days.
measure: Pharmacodynamic Outcomes for PT and the PT derived INR as measured by percent change over time.
timeFrame: For the PK Cohort: Patients will be followed for 72 days. For Cohorts A and B: Patients will be followed for 162 days.
Other outcomes:
measure: Pharmacokinetic Outcome for PK Cohort of effect of dialysis on peak concentrations
timeFrame: Patients will be followed for 29 days for this outcome measure.
measure: Pharmacokinetic Outcome for PK Cohort of effect of dialysis on partial area under the plasma concentration-time curve
timeFrame: Patients will be followed for 29 days for this outcome measure.
measure: Pharmacokinetic Outcome for Cohorts A and B to assess steady state concentrations
timeFrame: Patients will be followed for 162 days for this outcome measure
Locations:
city: Edmonton
country: Canada
facility: Ionis Investigative Site
state: Alberta
city: Halifax
country: Canada
facility: Ionis Investigative Site
state: Nova Scotia
city: Hamilton
country: Canada
facility: Ionis Investigative Site
state: Ontario
city: London
country: Canada
facility: Ionis Investigative Site
state: Ontario
city: Toronto
country: Canada
facility: Ionis Investigative Site
state: Ontario
city: Toronto
country: Canada
facility: Ionis Investigative Site
state: Ontario
city: Montreal
country: Canada
facility: Ionis Investigative Site
state: Quebec
city: Montreal
country: Canada
facility: Ionis Investigative Site
state: Quebec
Study officials:
affiliation: Ionis Pharmaceuticals
name: Sanjay Bhanot, MD
role: STUDY_DIRECTOR
References:
citation: Walsh M, Bethune C, Smyth A, Tyrwhitt J, Jung SW, Yu RZ, Wang Y, Geary RS, Weitz J, Bhanot S; CS4 Investigators. Phase 2 Study of the Factor XI Antisense Inhibitor IONIS-FXIRx in Patients With ESRD. Kidney Int Rep. 2021 Nov 24;7(2):200-209. doi: 10.1016/j.ekir.2021.11.011. eCollection 2022 Feb.