NCT02553889

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

Completed Phase 2 Last updated 12 December 2016

What this trial tests

Phase 2 trial testing ISIS 416858 in End-stage Renal Disease (ESRD) in 49 participants. Completed in 1 November 2016.

Timeline

1 October 2015

Primary endpoint
1 November 2016

1 November 2016

Quick facts

Lead sponsor	Ionis Pharmaceuticals, Inc.
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	prevention
Enrollment	49
Start date	1 October 2015
Primary completion	1 November 2016
Estimated completion	1 November 2016
Sites	8 locations across Canada

Drugs / interventions tested

• ISIS 416858 — full drug profile →
• Placebo

Conditions studied

• End-stage Renal Disease (ESRD) — all drugs for End-stage Renal Disease (ESRD) →

Sponsor

Ionis Pharmaceuticals, Inc. — full company profile →

Who can join

Adults 18 to 80, any sex, with End-stage Renal Disease (ESRD). Patients with the condition only — healthy volunteers not accepted.

What's being measured

Primary outcomes are the specific endpoints the trial is designed to prove or disprove.

• 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

Sponsor's own description

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

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Advances in the delivery of RNA therapeutics: from concept to clinical reality.
   Kaczmarek JC, Kowalski PS, Anderson DG. · · 2017 · cited 467× · PMID 28655327 · DOI 10.1186/s13073-017-0450-0
2. Antisense technology: A review.
   Crooke ST, Liang XH, Baker BF, Crooke RM. · · 2021 · cited 237× · PMID 33600796 · DOI 10.1016/j.jbc.2021.100416
3. Phase 2 Study of the Factor XI Antisense Inhibitor IONIS-FXI_Rx in Patients With ESRD.
   Walsh M, Bethune C, Smyth A, Tyrwhitt J, et al · · 2022 · cited 69× · PMID 35155859 · DOI 10.1016/j.ekir.2021.11.011
4. Factor XI Inhibitors for Prevention and Treatment of Venous Thromboembolism: A Review on the Rationale and Update on Current Evidence.
   Nopp S, Kraemmer D, Ay C. · · 2022 · cited 61× · PMID 35647061 · DOI 10.3389/fcvm.2022.903029
5. Recent advances in the discovery and development of factor XI/XIa inhibitors.
   Al-Horani RA, Afosah DK. · · 2018 · cited 60× · PMID 29727017 · DOI 10.1002/med.21503
6. The rebirth of the contact pathway: a new therapeutic target.
   Srivastava P, Gailani D. · · 2020 · cited 34× · PMID 32740037 · DOI 10.1097/moh.0000000000000603
7. Factor XI Inhibition for the Prevention of Venous Thromboembolism: An Update on Current Evidence and Future perspectives.
   Poenou G, Dumitru Dumitru T, Lafaie L, Mismetti V, et al · · 2022 · cited 26× · PMID 35707632 · DOI 10.2147/vhrm.s331614
8. Hemodialysis-Related Complement and Contact Pathway Activation and Cardiovascular Risk: A Narrative Review.
   Skinner SC, Derebail VK, Poulton CJ, Bunch DC, et al · · 2021 · cited 26× · PMID 34401728 · DOI 10.1016/j.xkme.2021.04.006