Inclisiran for Participants With Atherosclerotic Cardiovascular Disease and Elevated Low-density Lipoprotein Cholesterol

ASCVD Clinical Trial

— ORION-10  

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03399370
• Other study ID #: MDCO-PCS-17-04
• Status: Completed
• Phase: Phase 3
• Start date: December 21, 2017
• Est. completion date: September 17, 2019

Study information

• Verified date: September 2020
• Source: The Medicines Company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1561
• Est. completion date: September 17, 2019
• Est. primary completion date: September 10, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• ASCVD
• Atherosclerosis
• Cardiovascular Diseases
• Elevated Cholesterol
• Hypercholesterolemia

Intervention

Drug:
• Inclisiran Sodium
Inclisiran is a small interfering ribonucleic acid (RNA) that inhibits PCSK9 synthesis.
• Placebo
Placebo will be supplied as sterile normal saline (0.9% sodium chloride in water for injection).

Locations

Country	Name	City	State
United States	Research Site 10001-016	Akron	Ohio
United States	Research Site 10001-054	Albany	New York
United States	Research Site 10001-100	Amarillo	Texas
United States	Research Site 10001-001	Anderson	South Carolina
United States	Research Site 10001-059	Arlington Heights	Illinois
United States	Research Site 10001-146	Athens	Tennessee
United States	Research Site 10001-069	Atlanta	Georgia
United States	Research Site 10001-087	Austin	Texas
United States	Research Site 10001-117	Austin	Texas
United States	Research Site 10001-073	Beverly Hills	California
United States	Research Site 10001-122	Binghamton	New York
United States	Research Site 10001-015	Birmingham	Alabama
United States	Research Site 10001-047	Boca Raton	Florida
United States	Research Site 10001-060	Bridgewater	New Jersey
United States	Research Site 10001-050	Canoga Park	California
United States	Research Site 10001-011	Carlsbad	California
United States	Research Site 10001-063	Cary	North Carolina
United States	Research Site 10001-013	Chandler	Arizona
United States	Research Site 10001-035	Chicago	Illinois
United States	Research Site 10001-158	Chicago	Illinois
United States	Research Site 10001-010	Cincinnati	Ohio
United States	Research Site 10001-120	Cincinnati	Ohio
United States	Research Site 10001-134	Cincinnati	Ohio
United States	Research Site 10001-154	Cincinnati	Ohio
United States	Research Site 10001-084	Clearwater	Florida
United States	Research Site 10001-099	Clearwater	Florida
United States	Research Site 10001-155	Clearwater	Florida
United States	Research Site 10001-012	Columbus	Ohio
United States	Research Site 10001-014	Columbus	Ohio
United States	Research Site 10001-144	Crowley	Louisiana
United States	Research Site 10001-009	Dallas	Texas
United States	Research Site 10001-141	Dayton	Ohio
United States	Research Site 10001-127	Daytona Beach	Florida
United States	Research Site 10001-137	Dunwoody	Georgia
United States	Research Site 10001-018	Edina	Minnesota
United States	Research Site 10001-068	Edinburg	Texas
United States	Research Site 10001-017	Edmond	Oklahoma
United States	Research Site 10001-065	El Cajon	California
United States	Research Site 10001-128	Endwell	New York
United States	Research Site 10001-036	Evanston	Illinois
United States	Research Site 10001-093	Falls Church	Virginia
United States	Research Site 10001-119	Fleming Island	Florida
United States	Research Site 10001-024	Flint	Michigan
United States	Research Site 10001-138	Foley	Alabama
United States	Research Site 10001-070	Fort Lauderdale	Florida
United States	Research Site 10001-126	Fort Worth	Texas
United States	Research Site 10001-095	Grandville	Michigan
United States	Research Site 10001-064	Greensboro	North Carolina
United States	Research Site 10001-006	Greer	South Carolina
United States	Research Site 10001-075.	Greer	South Carolina
United States	Research Site 10001-067	Hialeah	Florida
United States	Research Site 10001-031	Houston	Texas
United States	Research Site 10001-032	Houston	Texas
United States	Research Site 10001-061	Houston	Texas
United States	Research Site 10001-088	Houston	Texas
United States	Research Site 10001-091	Houston	Texas
United States	Research Site 10001-113	Huntsville	Alabama
United States	Research Site 10001-028	Hutchinson	Kansas
United States	Research Site 10001-082	Indianapolis	Indiana
United States	Research Site 10001-039	Jacksonville	Florida
United States	Research Site 10001-098	Jacksonville	Florida
United States	Research Site 10001-139	Jacksonville	Florida
United States	Research Site 10001-130	Kingsport	Tennessee
United States	Research Site 10001-118	Knoxville	Tennessee
United States	Research Site 10001-041	Lake Charles	Louisiana
United States	Research Site 10001-112	Las Vegas	Nevada
United States	Research Site 10001-124	Las Vegas	Nevada
United States	Research Site 10001-005	Layton	Utah
United States	Research Site 10001-108	Lexington	Kentucky
United States	Research Site 10001-125	Lexington	Kentucky
United States	Research Site 10001-150	Los Angeles	California
United States	Research Site 10001-025	Lubbock	Texas
United States	Research Site 10001-092	Macon	Georgia
United States	Research Site 10001-085	Manassas	Virginia
United States	Research Site 10001-148	Marion	Ohio
United States	Research Site 10001-077	Mesa	Arizona
United States	Research Site 10001-030	Miami	Florida
United States	Research Site 10001-081	Miami	Florida
United States	Research Site 10001-089	Miami	Florida
United States	Research Site 10001-116	Miami	Florida
United States	Research Site 10001-140	Miami	Florida
United States	Research Site 10001-142	Miami	Florida
United States	Research Site 10001-080	Miami Springs	Florida
United States	Research Site 10001-094	Midlothian	Virginia
United States	Research Site 10001-058	Mobile	Alabama
United States	Research Site 10001-101	Monroe	Louisiana
United States	Research Site 10001-037	Montgomery	Alabama
United States	Research Site 10001-145	Mooresville	North Carolina
United States	Research Site 10001-111	Myrtle Beach	South Carolina
United States	Research Site 10001-057	New Braunfels	Texas
United States	Research Site 10001-042	New Windsor	New York
United States	Research Site 10001-022	Northridge	California
United States	Research Site 10001-043	Northridge	California
United States	Research Site 10001-021	Omaha	Nebraska
United States	Research Site 10001-053	Omaha	Nebraska
United States	Research Site 10001-107	Owensboro	Kentucky
United States	Research Site 10001-133	Pelzer	South Carolina
United States	Research Site 10001-027	Pembroke Pines	Florida
United States	Research Site 10001-048	Pembroke Pines	Florida
United States	Research Site 10001-115	Pembroke Pines	Florida
United States	Research Site 10001-147	Pembroke Pines	Florida
United States	Research Site 10001-136	Phoenix	Arizona
United States	Research Site 10001-003	Pinellas Park	Florida
United States	Research Site 10001-104	Ponte Vedra	Florida
United States	Research Site 10001-129	Poughkeepsie	New York
United States	Research Site 10001-106	Powell	Texas
United States	Research Site 10001-103	Rapid City	South Dakota
United States	Research Site 10001-055	Raritan	New Jersey
United States	Research Site 10001-023	Richmond	Virginia
United States	Research Site 10001-079	Round Rock	Texas
United States	Research Site 10001-033	Sacramento	California
United States	Research Site 10001-090	Saint Augustine	Florida
United States	Research Site 10001-007	Saint Louis	Missouri
United States	Research Site 10001-156	Saint Louis	Missouri
United States	Research Site 10001-056	Saint Paul	Minnesota
United States	Research Site 10001-102	Saint Petersburg	Florida
United States	Research Site 10001-002	Salt Lake City	Utah
United States	Research Site 10001-052	Salt Lake City	Utah
United States	Research Site 10001-071	San Antonio	Texas
United States	Research Site 10001-105	San Ramon	California
United States	Research Site 10001-008	Santa Rosa	California
United States	Research Site 10001-076	Saraland	Alabama
United States	Research Site 10001-123	Sarasota	Florida
United States	Research Site 10001-083	Schertz	Texas
United States	Research Site 1001-020	Sellersburg	Indiana
United States	Research Site 10001-149	Shavano Park	Texas
United States	Research Site 10001-046	Shelby	North Carolina
United States	Research Site 10001-026	Spartanburg	South Carolina
United States	Research Site 10001-153	Spring Valley	California
United States	Research Site 10001-078	Sterling Heights	Michigan
United States	Research Site 10001-029	Suffolk	Virginia
United States	Research Site 10001-051	Surprise	Arizona
United States	Research Site 10001-114	Tacoma	Washington
United States	Research Site 10001-038	Tampa	Florida
United States	Research Site 10001-143	Tampa	Florida
United States	Research Site 10001-045	Tomball	Texas
United States	Research Site 10001-044	Torrance	California
United States	Research Site 10001-034	Troy	Michigan
United States	Research Site 10001-004	Tucson	Arizona
United States	Research Site 10001-019	Tucson	Arizona
United States	Research Site 10001-132	Tucson	Arizona
United States	Research Site 10001-040	Valparaiso	Indiana
United States	Research Site 10001-074	West Des Moines	Iowa
United States	Research Site 10001-110	Williamsville	New York
United States	Research Site 10001-109	Wyomissing	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
The Medicines Company

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage Change in LDL-C From Baseline to Day 510		Baseline, Day 510
Primary	Time-adjusted Percentage Change in LDL-C Levels From Baseline After Day 90 and up to Day 540	Assessments performed at Baseline, Day 90, Day 540, time-adjusted percent change at Day 540 reported	Baseline, Day 90 to Day 540
Secondary	Absolute Change in LDL-C From Baseline to Day 510		Baseline, Day 510
Secondary	Time-adjusted Absolute Change in LDL-C From Baseline After Day 90 and up to Day 540	Assessments performed at Baseline, Day 90, Day 540, time-adjusted percent change at Day 540 reported	Baseline, Day 90 to Day 540
Secondary	Percentage Change in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) From Baseline to Day 510		Baseline, Day 510
Secondary	Percentage Change in Total Cholesterol From Baseline to Day 510		Baseline, Day 510
Secondary	Percentage Change in Apolipoprotein B (ApoB) From Baseline to Day 510		Baseline, Day 510
Secondary	Percentage Change in Non-HDL-C From Baseline to Day 510		Baseline, Day 510