End-stage Renal Disease (ESRD)Phase 2EMERALDNCT03358030
A Study of ISIS 416858 Administered Subcutaneously to Participants With End-Stage Renal Disease (ESRD) on Hemodialysis
A Phase 2 study testing ISIS 416858 in people with End-stage Renal Disease (ESRD), run by Ionis Pharmaceuticals, Inc. at 2 sites in Spain.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- End-stage Renal Disease (ESRD)
- What is being tested?
- ISIS 416858
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 213 participants
- Where
- 2 sitesSpain
- Study dates
- 26 Dec 2017to 10 Jul 2019
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 18Show fewer
- 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.
Trial locations and contacts
2 sites in 1 country.
Spain2 sites
Ionis Investigative Site
Alcalá de Henares, Madrid, 28805
Ionis Investigative Site
Santiago de Compostela, A Coruna, 15706
About this study
Official title: 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.
Read the 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.
- Conditions
- End-stage Renal Disease (ESRD)
- Being tested
- ISIS 416858, Placebo
- Medical subject headings
- Kidney Failure, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ISIS 416858Drug
Also called IONIS-FXIRx
Subcutaneous injection
PlaceboDrug
Also called 0.9% sterile saline, Riboflavin
Subcutaneous injection
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: 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. Receives: Drug: ISIS 416858 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up to Day 260
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Nov 2017
- Study start26 Dec 2017
- Primary completion10 Jul 2019
- Study completion10 Jul 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for End-stage Renal Disease (ESRD)Studies of the same condition, open and under way.
- More trials run by Ionis Pharmaceuticals, Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 213 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ionis Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Bayer
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03358030
- Sponsor's protocol ID
- ISIS 416858 CS5
- Other IDs
- 2017-002165-21, NL62709.000.17, 2017
- Acronym
- EMERALD
- Status last verified
- Dec 2022
- First submitted
- 13 Nov 2017
- Last updated
- 20 Jan 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Jan 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT03358030
- Acronym / sponsor ID
- EMERALD / ISIS 416858 CS5
- Conditions
- End-stage Renal Disease (ESRD)
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 213 participants (actual)
- Lead sponsor
- Ionis Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Collaborators
- Bayer
- Study start
- 26 Dec 2017 (actual)
- Primary completion
- 10 Jul 2019 (actual)
- Study completion
- 10 Jul 2019 (actual)
- First posted
- 30 Nov 2017 (actual)
- Results
- Posted 20 Jan 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: PlaceboParticipants received placebo, subcutaneously, within 2 hours post-dialysis, once weekly from Week 1 (Day 1) through Week 26 of treatment period. |
| Cohort A: ISIS 416858, 200 mg | Experimental | Drug: ISIS 416858Participants received ISIS 416858, 200 mg, subcutaneously, within 2 hours post-dialysis, once weekly from Week 1 (Day 1) through Week 26 of treatment period. |
| Cohort B: ISIS 416858, 250 mg | Experimental | Drug: ISIS 416858Participants received ISIS 416858, 250 mg, subcutaneously, within 2 hours post-dialysis, once weekly from Week 1 (Day 1) through Week 26 of treatment period. |
| Cohort C: ISIS 416858, 300 mg | Experimental | Drug: ISIS 416858Participants received ISIS 416858, 300 mg, subcutaneously, within 2 hours post-dialysis, once weekly from Week 1 (Day 1) through Week 26 of treatment period. |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- 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.
Key exclusion criteria (18 listed)
- 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:
- 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:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ISIS 416858Also: IONIS-FXIRxSubcutaneous injection | Drug | Cohort A: ISIS 416858, 200 mg, Cohort B: ISIS 416858, 250 mg, Cohort C: ISIS 416858, 300 mg |
| PlaceboAlso: 0.9% sterile saline, RiboflavinSubcutaneous injection | Drug | Placebo |
Primary outcome
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jan 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing ISIS 416858 in people with End-stage Renal Disease (ESRD), run by Ionis Pharmaceuticals, Inc. at 2 sites in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Jan 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 Jan 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Major Bleeding (MB) and Clinically Relevant Non-Major Bleeding (CRNMB) (time frame: Up to Day 260). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Jan 2023.