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Trial record 1 of 1 for:    akcea-apo(a)-Lrx | akcea [Lead] | Phase 2
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Phase 2 Study of ISIS 681257 (AKCEA-APO(a)-LRx) in Patients With Hyperlipoproteinemia(a) and Cardiovascular Disease

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ClinicalTrials.gov Identifier: NCT03070782
Recruitment Status : Completed
First Posted : March 6, 2017
Last Update Posted : December 13, 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

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 286 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
Actual Study Completion Date : November 13, 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

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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


Locations
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United States, Arizona
Clinical Site
Cottonwood, Arizona, United States, 86326
United States, California
Clinical Site
Huntington Beach, California, United States, 92648
Clinical Site
La Jolla, California, United States, 92103
Clinical Site
Los Angeles, California, United States, 90048
Clinical Site
Stanford, California, United States, 94305
United States, Colorado
Clinical Site
Colorado Springs, Colorado, United States, 80909
United States, Florida
Clinical Site
Boca Raton, Florida, United States, 33434
Clinical Site
Jacksonville, Florida, United States, 32216
United States, Kansas
Clinical Site
Kansas City, Kansas, United States, 66160
United States, Maryland
Clinical Site
Baltimore, Maryland, United States, 21201
United States, Massachusetts
Clinical Site
Boston, Massachusetts, United States, 02114
United States, New York
Clinical Site
Cooperstown, New York, United States, 13326
Clinical Site
New York, New York, United States, 10016
Clinical Site
New York, New York, United States, 10029
United States, Ohio
Clinical Site
Cleveland, Ohio, United States, 44195
United States, Oregon
Clinical Site
Portland, Oregon, United States, 97239
United States, Pennsylvania
Clinical Site
Lancaster, Pennsylvania, United States, 17602
Clinical Site
Philadelphia, Pennsylvania, United States, 19104
United States, Rhode Island
Clinical Site
Providence, Rhode Island, United States, 02906
United States, Texas
Clinical Site
Houston, Texas, United States, 77030
United States, Virginia
Clinical Site
Falls Church, Virginia, United States, 22042
United States, Wisconsin
Clinical Site
Milwaukee, Wisconsin, United States, 53215
Canada, Quebec
Clinical Site
Chicoutimi, Quebec, Canada, G7H7K9
Clinical Site
Montreal, Quebec, Canada, H1T 1C8
Clinical Site
Montréal, Quebec, Canada, H3H 2L9
Clinical Site
Québec, Quebec, Canada, G1V4W2
Canada
Clinical Site
Ottawa, Canada, K1Y4W7
Denmark
Clinical Site
Herlev, Denmark, 2730
Clinical Site
Viborg, Denmark, 8800
Germany
Clinical Site
Berlin, Germany, 13353
Clinical Site
Cologne, Germany, 50937
Netherlands
Clinical Site
Amsterdam, Netherlands, 1105AZ
Sponsors and Collaborators
Akcea Therapeutics
Ionis Pharmaceuticals, Inc.
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Akcea Therapeutics
ClinicalTrials.gov Identifier: NCT03070782    
Other Study ID Numbers: ISIS 681257-CS6
First Posted: March 6, 2017    Key Record Dates
Last Update Posted: December 13, 2018
Last Verified: December 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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:
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Hyperlipoproteinemias
Hyperlipidemias
Cardiovascular Diseases
Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases