A Study of ISIS 416858 Administered Subcutaneously to Participants With End-Stage Renal Disease (ESRD) on Hemodialysis

NCT03358030 | Completed Phase 2 Results FDA Drug

• 3 other identifiers: ISIS 416858 CS52017-002165-21NL62709.000.17
• Study Type: interventional
• Target: 213
• Locations: 1 country
• Sites: 2

Brief Summary

Evaluation of safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of ISIS 416858 for up to 204 participants with ESRD receiving chronic hemodialysis as assessed by FXI activity reduction.

Conditions

End-stage Renal Disease (ESRD)

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Major Bleeding (MB) and Clinically Relevant Non-Major Bleeding (CRNMB)

  MB was defined as one of the following: Fatal bleeding; symptomatic bleeding in a critical area or organ, such as intracranial, intraspinal, intraocular, retroperitoneal, intraarticular if in a major joint, or pericardial, or intramuscular with compartment syndrome, clinically overt bleeding leading to transfusion of greater than or equal to (\>=) 2 units of packed red blood cells or whole blood or a fall in hemoglobin of 20 grams per liter (g/L) (1.24 millimoles per liter \[mmol/L\]) or more within 24 hours. CRNMB was defined as overt bleeding not meeting the criteria for MB but that resulted, in either medical examination, intervention, or had clinical consequences for a participant.

  Up to Day 260

Other Outcomes (6)

• Percent Change From Baseline in Activated Partial Thromboplastin Time (aPTT)

  Baseline (Day 1) up to Day 260

• Percent Change From Baseline in Factor XI (FXI) Activity

  Baseline (Day 1) up to Day 260

• Number of Participants With Laboratory Abnormalities Related to Platelet Count

  Up to Day 260

Study Arms (4)

Placebo

PLACEBO COMPARATOR

Participants received placebo, subcutaneously, within 2 hours post-dialysis, once weekly from Week 1 (Day 1) through Week 26 of treatment period.

Drug: Placebo

Cohort A: ISIS 416858, 200 mg

EXPERIMENTAL

Participants received ISIS 416858, 200 mg, subcutaneously, within 2 hours post-dialysis, once weekly from Week 1 (Day 1) through Week 26 of treatment period.

Drug: ISIS 416858

Cohort B: ISIS 416858, 250 mg

EXPERIMENTAL

Participants received ISIS 416858, 250 mg, subcutaneously, within 2 hours post-dialysis, once weekly from Week 1 (Day 1) through Week 26 of treatment period.

Drug: ISIS 416858

Cohort C: ISIS 416858, 300 mg

EXPERIMENTAL

Participants received ISIS 416858, 300 mg, subcutaneously, within 2 hours post-dialysis, once weekly from Week 1 (Day 1) through Week 26 of treatment period.

Drug: ISIS 416858

Interventions

ISIS 416858 DRUG

Subcutaneous injection

Also known as: IONIS-FXIRx

Cohort A: ISIS 416858, 200 mg; Cohort B: ISIS 416858, 250 mg; Cohort C: ISIS 416858, 300 mg

Placebo DRUG

Subcutaneous injection

Also known as: 0.9% sterile saline, Riboflavin

Placebo

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• End stage renal disease maintained on outpatient hemodialysis at a healthcare center for \> 3 months from screening with hemodialysis at least 3 times per week for a minimum of 9 hours per week of prescribed treatment time and plan to continue this throughout the study.

You may not qualify if:

• Participants with a history of major medical event (previous acute coronary syndrome, stroke or transient ischemic attack or systemic thromboembolic event) within 3 months of screening, major surgery within 3 months of screening, or new major physical examination finding except for documented atrial fibrillation
• Active bleeding within the past 3 months from screening or documented bleeding diathesis (excluding uremia), coagulopathy, or recent prolonged compression time at arteriovenous fistula
• Screening values of:
• Platelet count \< 150,000 cells per millimeter cube (cells/mm\^3)
• \< 180,000 cells/mm\^3 for platelet function/activation subgroup
• International normalized ratio (INR) \> 1.4
• Activated partial thromboplastin time (aPTT) \> upper limit of normal (ULN)
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> 2 x ULN
• Total bilirubin \> ULN
• Factor XI (FXI) activity \< 0.3 units per milliliter (U/mL)
• Malignancy within 5 years, except basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix that has been successfully treated. Participants with malignancies that have been treated with curative intent and which have no reoccurrence within 5 years may also be eligible if approved by Sponsor Medical Monitor.
• Within 6 months prior to screening, have any of the following:
• More than 3 episodes of severe hypoglycemia requiring the assistance of another person to actively administer carbohydrate, glucagon or other resuscitative actions
• One event of hypoglycemia in which the participant required hospitalization
• Recurrent syncope and recurrent hypotension in the inter-dialytic period requiring intervention

Sponsors & Collaborators

• Ionis Pharmaceuticals, Inc.: lead
• Bayer: collaborator

Study Sites (2)

Ionis Investigative Site

Santiago de Compostela, A Coruna, 15706, Spain

Location

Ionis Investigative Site

Alcalá de Henares, Madrid, 28805, Spain

Location

MeSH Terms

Conditions

Kidney Failure, Chronic

Interventions

ISIS 416858; Riboflavin

Condition Hierarchy (Ancestors)

Renal Insufficiency, Chronic; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Flavins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 3-Ring; Coenzymes; Enzymes and Coenzymes; Pigments, Biological; Biological Factors

Results Point of Contact

• Title: Ionis Pharmaceuticals, Inc.
• Organization: Ionis Pharmaceuticals, Inc.

patients@ionisph.com

800-679-4747

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 13, 2017
• First Posted: November 30, 2017
• Study Start: December 26, 2017
• Primary Completion: July 10, 2019
• Study Completion: July 10, 2019
• Last Updated: January 20, 2023
• Results First Posted: January 20, 2023

Record last verified: 2022-12

Data Sharing

• IPD Sharing: Will not share

Locations

ES (2)