Clinical trial NCT03399370: Inclisiran for Participants With Atherosclerotic Cardiovascular Disease and Elevated Low-density Lipoprotein Cholesterol
Official title: A Placebo-Controlled, Double-Blind, Randomized Trial to Evaluate the Effect of 300 mg of Inclisiran Sodium Given as Subcutaneous Injections in Subjects With Atherosclerotic Cardiovascular Disease (ASCVD) and Elevated Low-Density Lipoprotein Cholesterol (LDL-C)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: ASCVD
Elevated Cholesterol
Keywords: Inclisiran sodium
ASCVD
LDL-C
Lead sponsor: The Medicines Company
Sponsor class: INDUSTRY
First posted: 2018-01-16
Enrollment: 1561
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a Phase III, placebo-controlled, double-blind, randomized study in participants with ASCVD and elevated LDL-C despite maximum tolerated dose of LDL-C lowering therapies to evaluate the efficacy, safety, and tolerability of subcutaneous (SC) inclisiran injection(s). The study will be a multicenter study in the United States.


Eligibility criteria: Inclusion Criteria:

1. Male or female participants ≥18 years of age.
2. History of ASCVD (coronary heart disease \[CHD\], cardiovascular disease \[CVD\], or peripheral arterial disease \[PAD\]).
3. Serum LDL-C ≥1.8 millimole (mmol)/liter (L) (≥70 mg/dL).
4. Fasting triglyceride \<4.52 mmol/L (\<400 mg/dL) at screening.
5. Participants on statins should be receiving a maximally tolerated dose.
6. Participants not receiving statins must have documented evidence of intolerance to all doses of at least 2 different statins.
7. Subjects on lipid-lower therapies (such as a statin and/or ezetimibe) should be on a stable dose for ≥30 days before screening with no planned medication or dose change during study participation.

Exclusion Criteria:

1. New York Heart Association (NYHA) class IV heart failure.
2. Uncontrolled cardiac arrhythmia
3. Uncontrolled severe hypertension
4. Active liver disease
5. Females who are pregnant or nursing, or who are of childbearing potential and unwilling to use at least 2 methods of highly effective contraception (failure rate less than 1% per year) (for example, combined oral contraceptives, barrier methods, approved contraceptive implant, long-term injectable contraception, or intrauterine device) for the entire duration of the study. Exemptions from this criterion:

   1. Women \>2 years postmenopausal (defined as 1 year or longer since last menstrual period) and more than 55 years of age.
   2. Postmenopausal women (as defined above) and less than 55 years of age with a negative pregnancy test within 24 hours of randomization.
   3. Women who are surgically sterilized at least 3 months prior to enrollment.
6. Males who are unwilling to use an acceptable method of birth control during the entire study period (such as condom with spermicide).
7. Treatment with other investigational products or devices within 30 days or 5 half-lives of the screening visit, whichever is longer.
8. Treatment (within 90 days of screening) with monoclonal antibodies directed towards PCSK9

The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Primary outcomes:
measure: Percentage Change in LDL-C From Baseline to Day 510
timeFrame: Baseline, Day 510
measure: Time-adjusted Percentage Change in LDL-C Levels From Baseline After Day 90 and up to Day 540
timeFrame: Baseline, Day 90 to Day 540
Secondary outcomes:
measure: Absolute Change in LDL-C From Baseline to Day 510
timeFrame: Baseline, Day 510
measure: Time-adjusted Absolute Change in LDL-C From Baseline After Day 90 and up to Day 540
timeFrame: Baseline, Day 90 to Day 540
measure: Percentage Change in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) From Baseline to Day 510
timeFrame: Baseline, Day 510
measure: Percentage Change in Total Cholesterol From Baseline to Day 510
timeFrame: Baseline, Day 510
measure: Percentage Change in Apolipoprotein B (ApoB) From Baseline to Day 510
timeFrame: Baseline, Day 510
measure: Percentage Change in Non-HDL-C From Baseline to Day 510
timeFrame: Baseline, Day 510
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Research Site 10001-015
state: Alabama
city: Foley
country: United States
facility: Research Site 10001-138
state: Alabama
city: Huntsville
country: United States
facility: Research Site 10001-113
state: Alabama
city: Mobile
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facility: Research Site 10001-058
state: Alabama
city: Montgomery
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city: Jacksonville
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facility: Research Site 10001-039
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facility: Research Site 10001-098
state: Florida
city: Miami Springs
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city: Miami
country: United States
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country: United States
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state: Florida
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facility: Research Site 10001-030
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country: United States
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state: Florida
city: Saint Augustine
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country: United States
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city: Atlanta
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state: Georgia
city: Dunwoody
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city: Chicago
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city: Lexington
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city: Owensboro
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country: United States
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city: Lake Charles
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city: Flint
country: United States
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city: Grandville
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city: Binghamton
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city: Endwell
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city: Cincinnati
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city: Greer
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state: South Carolina
city: Greer
country: United States
facility: Research Site 10001-075.
state: South Carolina
city: Myrtle Beach
country: United States
facility: Research Site 10001-111
state: South Carolina
city: Pelzer
country: United States
facility: Research Site 10001-133
state: South Carolina
city: Spartanburg
country: United States
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state: South Carolina
city: Rapid City
country: United States
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state: South Dakota
city: Athens
country: United States
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state: Tennessee
city: Kingsport
country: United States
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state: Tennessee
city: Knoxville
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state: Tennessee
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country: United States
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state: Texas
city: Austin
country: United States
facility: Research Site 10001-087
state: Texas
city: Austin
country: United States
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state: Texas
city: Dallas
country: United States
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state: Texas
city: Edinburg
country: United States
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city: Fort Worth
country: United States
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state: Texas
city: Houston
country: United States
facility: Research Site 10001-031
state: Texas
city: Houston
country: United States
facility: Research Site 10001-088
state: Texas
city: Houston
country: United States
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state: Texas
city: Houston
country: United States
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state: Texas
city: Houston
country: United States
facility: Research Site 10001-032
state: Texas
city: Lubbock
country: United States
facility: Research Site 10001-025
state: Texas
city: New Braunfels
country: United States
facility: Research Site 10001-057
state: Texas
city: Powell
country: United States
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state: Texas
city: Round Rock
country: United States
facility: Research Site 10001-079
state: Texas
city: San Antonio
country: United States
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state: Texas
city: Schertz
country: United States
facility: Research Site 10001-083
state: Texas
city: Shavano Park
country: United States
facility: Research Site 10001-149
state: Texas
city: Tomball
country: United States
facility: Research Site 10001-045
state: Texas
city: Layton
country: United States
facility: Research Site 10001-005
state: Utah
city: Salt Lake City
country: United States
facility: Research Site 10001-002
state: Utah
city: Salt Lake City
country: United States
facility: Research Site 10001-052
state: Utah
city: Falls Church
country: United States
facility: Research Site 10001-093
state: Virginia
city: Manassas
country: United States
facility: Research Site 10001-085
state: Virginia
city: Midlothian
country: United States
facility: Research Site 10001-094
state: Virginia
city: Richmond
country: United States
facility: Research Site 10001-023
state: Virginia
city: Suffolk
country: United States
facility: Research Site 10001-029
state: Virginia
city: Tacoma
country: United States
facility: Research Site 10001-114
state: Washington
Study officials:
affiliation: Mayo Clinic
name: Scott Wright, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ray KK, Wright RS, Kallend D, Koenig W, Leiter LA, Raal FJ, Bisch JA, Richardson T, Jaros M, Wijngaard PLJ, Kastelein JJP; ORION-10 and ORION-11 Investigators. Two Phase 3 Trials of Inclisiran in Patients with Elevated LDL Cholesterol. N Engl J Med. 2020 Apr 16;382(16):1507-1519. doi: 10.1056/NEJMoa1912387. Epub 2020 Mar 18.