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

NCT ID: NCT02553889

Last Updated: 2016-12-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 49 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-10-31
• Study Completion Date: 2016-11-30

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.

Conditions

End-stage Renal Disease (ESRD)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

PK Cohort

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).

Group Type: EXPERIMENTAL

ISIS 416858

Intervention Type: DRUG

subcutaneous injection

Cohort A

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.

Group Type: PLACEBO_COMPARATOR

ISIS 416858

Intervention Type: DRUG

subcutaneous injection

Placebo

Intervention Type: DRUG

subcutaneous injection

Cohort B

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.

Group Type: PLACEBO_COMPARATOR

ISIS 416858

Intervention Type: DRUG

subcutaneous injection

Placebo

Intervention Type: DRUG

subcutaneous injection

Interventions

ISIS 416858

subcutaneous injection

Intervention Type: DRUG

Placebo

subcutaneous injection

Intervention Type: DRUG

Other Intervention Names

ISIS-FXI Rx; BAY2306001; IONIS-FXI Rx; 0.9% sterile saline

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)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bayer

INDUSTRY

Sponsor Role: collaborator

Ionis Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sanjay Bhanot, MD

Role: STUDY_DIRECTOR

Ionis Pharmaceuticals

Locations

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

Toronto, Ontario, Canada

Ionis Investigative Site

Toronto, Ontario, Canada

Ionis Investigative Site

Montreal, Quebec, Canada

Ionis Investigative Site

Montreal, Quebec, Canada

Countries

Canada

References

Natale P, Palmer SC, Ruospo M, Longmuir H, Dodds B, Prasad R, Batt TJ, Jose MD, Strippoli GF. Anticoagulation for people receiving long-term haemodialysis. Cochrane Database Syst Rev. 2024 Jan 8;1(1):CD011858. doi: 10.1002/14651858.CD011858.pub2.

Reference Type: DERIVED

PMID: 38189593 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 35155859 (View on PubMed)

Other Identifiers

ISIS 416858 CS4

Identifier Type: -

Identifier Source: org_study_id