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

December 22, 2022 updated by: Ionis Pharmaceuticals, Inc.

A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study of the Safety, Pharmacokinetics, and Pharmacodynamics of Multiple Doses of ISIS 416858 (IONIS-FXIRX, an Antisense Inhibitor of Factor XI), Administered Subcutaneously to Patients With End-Stage Renal Disease on Hemodialysis

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Evaluation of safety, PK, and PD of ISIS 416858 (Dose # 1, Dose #2 and Dose #3 once weekly) as compared to placebo as assessed by FXI activity reduction.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
213

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Spain
    • A Coruna
      • Santiago De Compostela, A Coruna, Spain, 15706
        • Ionis Investigative Site
    • Madrid
      • Alcalá De Henares, Madrid, Spain, 28805
        • Ionis Investigative Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 85 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

• 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.

Exclusion Criteria:

  • 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
  • Planned major surgery in the next 6 months, including participants receiving kidney transplant or participants that anticipate changing dialysis modality (i.e. hemodialysis to peritoneal dialysis)
  • Concomitant use of anticoagulant/antiplatelet agents (e.g., warfarin, dabigatran, rivaroxaban, clopidogrel) that may affect coagulation (except low dose aspirin (≤ 100 mg/day) during Treatment and Post-treatment Evaluation Periods is not allowed. Stable does of heparins during dialysis are permitted
  • Uncontrolled hypertension as judged by the Investigator. Participants with a pre- or post-dialysis blood pressure (BP) that is > 180 millimeters of mercury (mmHg) on at least 3 of last 5 dialysis treatments.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Placebo Comparator: Placebo
Participants received placebo, subcutaneously, within 2 hours post-dialysis, once weekly from Week 1 (Day 1) through Week 26 of treatment period.
Drug: Placebo
Subcutaneous injection
Other Names:
  • Riboflavin
  • 0.9% sterile saline
Experimental: Cohort A: ISIS 416858, 200 mg
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
Subcutaneous injection
Other Names:
  • IONIS-FXIRx
Experimental: Cohort B: ISIS 416858, 250 mg
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
Subcutaneous injection
Other Names:
  • IONIS-FXIRx
Experimental: Cohort C: ISIS 416858, 300 mg
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
Subcutaneous injection
Other Names:
  • IONIS-FXIRx

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Number of Participants With Major Bleeding (MB) and Clinically Relevant Non-Major Bleeding (CRNMB)
Time Frame: Up to Day 260
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 Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Percent Change From Baseline in Activated Partial Thromboplastin Time (aPTT)
Time Frame: Baseline (Day 1) up to Day 260
Baseline (Day 1) up to Day 260
Percent Change From Baseline in Factor XI (FXI) Activity
Time Frame: Baseline (Day 1) up to Day 260
Baseline (Day 1) up to Day 260
Number of Participants With Laboratory Abnormalities Related to Platelet Count
Time Frame: Up to Day 260
Participants were assessed based on pre-defined criteria in the protocol for platelet count abnormality: 100 - less than (<)140, 75 - <100, 50 - <75, 25 - <50 and < 25 thousands per cubic millimeter (K/mm^3) based on investigator's discretion.
Up to Day 260
Number of Participants With Laboratory Abnormalities - Alanine Transaminase (ALT) and Aspartate Aminotransferase (AST)
Time Frame: Up to Day 260
Participants were assessed based on pre-defined criteria in protocol for abnormality in ALT and AST values: Confirmed ALT (serum glutamic pyruvic transaminase [SGPT]); greater than (>) 3*Upper limit of normal range (ULN), >5*ULN and confirmed AST (serum glutamic-oxaloacetic transaminase [SGOT]); >3*ULN and >5*ULN. A confirmed value was based on a consecutive lab value within 7 days of the initial value. If that value was in the same or worse category the initial value was confirmed. If the consecutive value was in a better category then the initial value was confirmed using the consecutive value category. If there were multiple results on the same day, no matter from the same lab vendor or different lab vendors, then the worst value was used in the analysis. Abnormality in laboratory parameter was based on investigator's discretion.
Up to Day 260
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Time Frame: Up to Day 260
Up to Day 260
Percent Change From Baseline in Factor XI (FXI) Antigen Levels
Time Frame: Baseline (Day 1) up to Day 260
Baseline (Day 1) up to Day 260

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Ionis Pharmaceuticals, Inc.

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Bayer

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Sanjay Bhanot, MD PhD, Ionis Pharmaceuticals

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 26, 2017

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 10, 2019

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 10, 2019

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 13, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 24, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 30, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
January 20, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 22, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • ISIS 416858 CS5
  • 2017-002165-21 (EudraCT Number)
  • NL62709.000.17 (Other Identifier: Central Committee on Research Involving Human Subjects (CCMO))

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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