ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 1 for:    AKCEA-APO(a)-LRx
Previous Study | Return to List | Next Study

Phase 2 Study of ISIS 681257 (AKCEA-APO(a)-LRx) in Patients With Hyperlipoproteinemia(a) and Cardiovascular Disease

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03070782
Recruitment Status : Active, not recruiting
First Posted : March 6, 2017
Last Update Posted : October 24, 2018
Sponsor:
Collaborator:
Ionis Pharmaceuticals, Inc.
Information provided by (Responsible Party):
Akcea Therapeutics

Brief Summary:
This is a multicenter, randomized, double-blind, placebo-controlled, dose-ranging study to evaluate the safety, including tolerability, of ISIS 681257 and to assess the efficacy of different doses and dosing regimens of ISIS 681257 for reduction of plasma Lp(a) levels in patients with hyperlipoproteinemia(a) and established cardiovascular disease (CVD).

Condition or disease Intervention/treatment Phase
Elevated Lipoprotein(a) Cardiovascular Disease Drug: ISIS 681257 Drug: Placebo Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 270 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-blind, Placebo-Controlled, Dose-Ranging Phase 2 Study of ISIS 681257 (AKCEA-APO(a)-LRx) Administered Subcutaneously to Patients With Hyperlipoproteinemia(a) and Established Cardiovascular Disease (CVD)
Actual Study Start Date : March 7, 2017
Actual Primary Completion Date : July 18, 2018
Estimated Study Completion Date : November 2018

Arm Intervention/treatment
Experimental: ISIS 681257 Dose 1
Cohort A
Drug: ISIS 681257
Randomly assigned to one of the dosing cohorts.
Other Name: AKCEA-APO(a)-LRx, IONIS-APO(a)-LRx

Experimental: ISIS 681257 Dose 2
Cohort B
Drug: ISIS 681257
Randomly assigned to one of the dosing cohorts.
Other Name: AKCEA-APO(a)-LRx, IONIS-APO(a)-LRx

Experimental: ISIS 681257 Dose 3
Cohort C
Drug: ISIS 681257
Randomly assigned to one of the dosing cohorts.
Other Name: AKCEA-APO(a)-LRx, IONIS-APO(a)-LRx

Experimental: ISIS 681257 Dose 4
Cohort D
Drug: ISIS 681257
Randomly assigned to one of the dosing cohorts.
Other Name: AKCEA-APO(a)-LRx, IONIS-APO(a)-LRx

Experimental: ISIS 681257 Dose 5
Cohort E
Drug: ISIS 681257
Randomly assigned to one of the dosing cohorts.
Other Name: AKCEA-APO(a)-LRx, IONIS-APO(a)-LRx

Placebo Comparator: Placebo: Sterile Normal Saline
Sterile Normal Saline (0.9% NaCl) by volume to match dose and regimen of active comparator depending on Cohort assignment
Drug: Placebo
Randomly assigned to one of the dosing cohorts. Dose of placebo in each cohort will match volume of active in that cohort.
Other Name: Sterile Normal Saline (0.9% NaCl)




Primary Outcome Measures :
  1. Percent change in plasma Lp(a) from baseline at the primary analysis time point for ISIS 681257 treatment groups compared to placebo. [ Time Frame: 6 months ]
    Analysis will be the comparison of percent change from baseline to primary analysis time point in fasting Lp(a) between ISIS 681257 treatment groups and pooled placebo group.

  2. Safety and tolerability of different doses and dosing regimens of ISIS 681257 as measured by proportion of patients with treatment-related adverse events by severity, and number of patients meeting safety stopping rules [ Time Frame: 6 months and 12 months ]
    The safety and tolerability of ISIS 681257 will be assessed by determining the incidence, severity, and dose relationship of adverse effects and changes in the laboratory parameters by dose. Safety results in subjects dosed with ISIS 681257 will be compared with those from subjects dosed with placebo.


Secondary Outcome Measures :
  1. Evaluate the effect of ISIS 681257 on the percent change from baseline in LDL-C. [ Time Frame: 6 months ]
    Percent change from baseline at the primary analysis time point in fasting LDL-C will be compared between each ISIS 681257 treatment groups and pooled placebo group.

  2. Evaluate the effect of ISIS 681257 on the proportion of patients who achieve plasma Lp(a) ≤ 50 mg/dL. [ Time Frame: 6 months ]
    Proportion of patients who achieve ≤ 50 mg/dL in fasting Lp(a) at the primary analysis time point will be compared between each ISIS 681257 treatment group and pooled placebo group.

  3. Evaluate the effect of ISIS 681257 on the percent change from baseline in plasma levels of apolipoprotein B (apoB). [ Time Frame: 6 months ]
    Percent change from baseline at the primary analysis time point in fasting apoB will be compared between ISIS 681257 treatment groups and pooled placebo group.

  4. Evaluate the effect of ISIS 681257 on the percent change from baseline in plasma levels of oxidized phospholipids (OxPL) on apolipoprotein (a) [apo(a)] [OXPL-apo(a)]. [ Time Frame: 6 months ]
    Percent change from baseline at the primary analysis time point in fasting OxPL apo(a) will be compared between ISIS 681257 treatment groups and pooled placebo group.

  5. Evaluate the effect of ISIS 681257 on the percent change from baseline in plasma levels of oxidized phospholipids (OxPL) on apoB (OXPL-apoB). [ Time Frame: 6 months ]
    Percent change from baseline at the primary analysis time point in fasting OxPL-apoB will be compared between ISIS 681257 treatment groups and pooled placebo group.


Other Outcome Measures:
  1. To evaluate plasma Cmax of ISIS 681257 across different doses and dose regimens. [ Time Frame: 6 months ]
    Cmax will be calculated for the treatment groups.

  2. To evaluate plasma Tmax of ISIS 681257 across different doses and dose regimens. [ Time Frame: 6 months ]
    Tmax will be calculated for the treatment groups.

  3. To evaluate plasma AUC values of ISIS 681257 across different doses and dose regimens. [ Time Frame: 6 months ]
    AUC values will be calculated for the treatment groups.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • Clinical diagnosis of CVD defined as documented coronary artery disease, stroke, or peripheral artery disease
  • Lp(a) plasma level ≥ 60 mg/dL
  • Must be on standard-of-care preventative therapy for other than elevated Lp(a) CVD risk factors

Key Exclusion Criteria:

  • Within 6 months of Screening: acute coronary syndrome, major cardiac surgery, or stroke/TIA
  • Within 3 months of Screening: coronary, carotid, or peripheral arterial revascularization, major non-cardiac surgery, or lipoprotein apheresis
  • Heart failure New York Heart Association (NYHA) class IV

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03070782


  Show 32 Study Locations
Sponsors and Collaborators
Akcea Therapeutics
Ionis Pharmaceuticals, Inc.

Responsible Party: Akcea Therapeutics
ClinicalTrials.gov Identifier: NCT03070782     History of Changes
Other Study ID Numbers: ISIS 681257-CS6
First Posted: March 6, 2017    Key Record Dates
Last Update Posted: October 24, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Akcea Therapeutics:
IONIS-APO(a)-LRx
AKCEA-APO(a)-LRx
Hyperlipoproteinemia(a)
Hyperlipoproteinemia a
Lipoprotein(a)
Lipoprotein a
Lp(a)
Lp a
Dyslipidemia
Dyslipoproteinemia
Hyperlipidemia
Hyperlipoproteinemia
Lipoprotein

Additional relevant MeSH terms:
Cardiovascular Diseases
Hyperlipoproteinemias
Hyperlipidemias
Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases