End-stage Renal Disease (ESRD)Phase 2NCT02553889
A Study of Safety, PK, & PD of ISIS 416858 Administered Subcutaneously to Patients With End-Stage Renal Disease on Hemodialysis
A Phase 2 study testing ISIS 416858 in people with End-stage Renal Disease (ESRD), run by Ionis Pharmaceuticals, Inc. at 8 sites in Canada.
Trial summary
Evaluation of safety, tolerability, PK and PD of ISIS 416858 in patients with end-stage renal disease (ESRD) receiving chronic hemodialysis. Read more about this study
- Who is it for?
- Ages 18 to 80 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
- 49 participants
- Where
- 8 sitesCanada
- Study dates
- Oct 2015to Nov 2016
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 80 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 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.
Who cannot join
- 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:
Show all 11Show fewer
- 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)
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
Canada8 sites
Ionis Investigative Site
Edmonton, Alberta, T6G 2P4
Ionis Investigative Site
Halifax, Nova Scotia, B3H 1V8
Ionis Investigative Site
Hamilton, Ontario, L8N 4A6
Ionis Investigative Site
London, Ontario, N6A 5W9
Ionis Investigative Site
Montreal, Quebec, H2X 0A9
Ionis Investigative Site
Montreal, Quebec, H4J 1C5
Ionis Investigative Site
Toronto, Ontario, M5B 1W8
Ionis Investigative Site
Toronto, Ontario, M9N 1N8
About this study
Official title: 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
Evaluation of safety, tolerability, PK and PD of ISIS 416858 in patients with end-stage renal disease (ESRD) receiving chronic hemodialysis.
Read the 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)
- 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 ISIS-FXI Rx, BAY2306001, IONIS-FXI Rx
subcutaneous injection
PlaceboDrug
Also called 0.9% sterile saline
subcutaneous injection
| Study group | Role | What they receive |
|---|---|---|
| PK Cohort | Experimental | 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). Receives: Drug: ISIS 416858 |
| Cohort A | Placebo comparator | 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. Receives: Drug: ISIS 416858; Drug: Placebo |
| Cohort B | Placebo comparator | 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. Receives: Drug: ISIS 416858; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
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
Measured: For the PK Cohort: Patients will be followed for 72 days. For Cohorts A and B: Patients will be followed for 162 days.
Secondary outcomes (6)
Pharmacodynamic Outcomes in FXI antigen and activity as measured by absolute change over time.
Pharmacodynamic Outcomes as measured by absolute change over time for FXI antigen and activity (units/milliliter)
Measured: For the PK Cohort: Patients will be followed for 72 days. For Cohorts A and B: Patients will be followed for 162 days.
Pharmacodynamic Outcomes in FXI antigen and activity as measured by percent change over time.
Pharmacodynamic Outcomes as measured by percent change over time for FXI antigen and activity (units/milliliter)
Measured: For the PK Cohort: Patients will be followed for 72 days. For Cohorts A and B: Patients will be followed for 162 days.
Pharmacodynamic Outcomes in aPTT as measured by absolute change over time.
Pharmacodynamic Outcomes as measured by absolute change over time for aPTT (seconds)
Measured: For the PK Cohort: Patients will be followed for 72 days. For Cohorts A and B: Patients will be followed for 162 days.
Pharmacodynamic Outcomes in aPTT as measured by percent change over time.
Pharmacodynamic Outcomes as measured by percent change over time for aPTT (seconds)
Measured: For the PK Cohort: Patients will be followed for 72 days. For Cohorts A and B: Patients will be followed for 162 days.
Pharmacodynamic Outcomes for PT and the PT derived INR as measured by absolute change over time.
Pharmacodynamic Outcomes as measured by absolute change over time for PT (seconds) and the PT derived INR (International Normalization Ratio)
Measured: For the PK Cohort: Patients will be followed for 72 days. For Cohorts A and B: Patients will be followed for 162 days.
Pharmacodynamic Outcomes for PT and the PT derived INR as measured by percent change over time.
Pharmacodynamic Outcomes as measured by percent change over time for PT (seconds) and the PT derived INR (International Normalization Ratio)
Measured: For the PK Cohort: Patients will be followed for 72 days. For Cohorts A and B: Patients will be followed for 162 days.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Sep 2015 (estimated)
- Study startOct 2015
- Primary completionNov 2016
- Study completionNov 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- 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
- 49 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ionis Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Bayer
- Responsible party
- Sponsor
- Investigators
- Sanjay Bhanot, MD, Study director, Ionis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02553889
- Sponsor's protocol ID
- ISIS 416858 CS4
- Status last verified
- Dec 2016
- First submitted
- 14 Sep 2015
- Last updated
- 13 Dec 2016
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 38189593Walsh 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.
PubMed 35155859
Study at a glance
From the registry record, last updated by the sponsor on 13 Dec 2016. 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, PK, and PD of Multiple Doses of ISIS 416858 (ISIS-FXI RX), Administered Subcutaneously to Patients With End-Stage Renal Disease on Hemodialysis
- ClinicalTrials.gov ID
- NCT02553889
- Acronym / sponsor ID
- ISIS 416858 CS4
- Conditions
- End-stage Renal Disease (ESRD)
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 49 participants (actual)
- Lead sponsor
- Ionis Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Collaborators
- Bayer
- Study start
- Oct 2015
- Primary completion
- Nov 2016 (actual)
- Study completion
- Nov 2016 (actual)
- First posted
- 18 Sep 2015 (estimated)
- Results
- Not posted in the source record
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, 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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| PK Cohort | Experimental | Drug: ISIS 416858A 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). |
| Cohort A | Placebo comparator | Drug: ISIS 416858, Drug: PlaceboPatients 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. |
| Cohort B | Placebo comparator | Drug: ISIS 416858, Drug: PlaceboPatients 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. |
Who may qualify
- Ages
- 18 to 80 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 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.
Key exclusion criteria (11 listed)
- 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:
- Abnormal liver function at Screening:
- 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.
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: ISIS-FXI Rx, BAY2306001, IONIS-FXI Rxsubcutaneous injection | Drug | Cohort A, Cohort B, PK Cohort |
| PlaceboAlso: 0.9% sterile salinesubcutaneous injection | Drug | Cohort A, Cohort B |
Primary outcome
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
6 secondary outcomes
Pharmacodynamic Outcomes in FXI antigen and activity as measured by absolute change over time.
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.
Pharmacodynamic Outcomes in FXI antigen and activity as measured by percent change over time.
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.
Pharmacodynamic Outcomes in aPTT as measured by absolute change over time.
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.
Pharmacodynamic Outcomes in aPTT as measured by percent change over time.
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.
Pharmacodynamic Outcomes for PT and the PT derived INR as measured by absolute change over time.
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.
Pharmacodynamic Outcomes for PT and the PT derived INR as measured by percent change over time.
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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Dec 2016.
- Derived from this study: PubMed 38189593Natale 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.
- Derived from this study: PubMed 35155859Walsh 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.
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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.
Sanjay Bhanot, MD study director
Ionis Pharmaceuticals
8 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 8 sites in Canada.
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 11 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 13 Dec 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in Canada. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02553889, which also lists 2 linked publications.
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 13 Dec 2016.