Trial to Assess the Effect of Long Term Dosing of Inclisiran in Subjects With High CV Risk and Elevated LDL-C

An Open-label Extension Trial of the Phase III Lipid-lowering Trials to Assess the Effect of Long Term Dosing of Inclisiran Given as Subcutaneous Injections in Subjects With High Cardiovascular Risk and Elevated LDL-C

Sponsors

Lead Sponsor: The Medicines Company

Source The Medicines Company
Brief Summary

The purpose of this extension study is to evaluate the efficacy, safety, and tolerability of long-term dosing of Inclisiran. The study will be a global multicenter study.

Detailed Description

This study will be an open label, long term extension study in subjects with atherosclerotic cardiovascular disease (ASCVD), ASCVD-risk equivalents (eg, diabetes and familial hypercholesterolemia), or heterozygous or homozygous familial hypercholesterolemia (HeFH or HoFH) and elevated low density lipoprotein cholesterol (LDL-C) despite maximum tolerated dose of LDL-C lowering therapies who have completed any of the following inclisiran Phase III lipid lowering studies: MDCO-PCS-17-03 (ORION-9), MDCO-PCS-17-04 (ORION-10), MDCO-PCS-17-08 (ORION-11) or MDCO-PCS-17-02 (ORION-5).

Overall Status Active, not recruiting
Start Date April 16, 2019
Completion Date December 2023
Primary Completion Date August 2023
Phase Phase 3
Study Type Interventional
Primary Outcome
Measure Time Frame
Proportion of subjects reaching on treatment LDL-C targets of <70 mg/dL Day 1080
Proportion of subjects reaching on treatment LDL-C targets of <100 mg/dL Day 1080
Secondary Outcome
Measure Time Frame
Evaluate the effect of inclisiran on LDL-C levels Baseline, Day 1080
Evaluate the effect of inclisiran on total cholesterol (TC), triglycerides, LDL-C, and high density lipoprotein cholesterol (HDL-C) Baseline, Day 1080
Enrollment 2991
Condition
Intervention

Intervention Type: Drug

Intervention Name: Inclisiran Sodium

Description: Inclisiran is a small interfering ribonucleic acid (RNA) that inhibits PCSK9 synthesis.

Arm Group Label: Inclisiran

Eligibility

Criteria:

Inclusion Criteria:

1. Completion of a previously qualifying Phase III lipid-lowering ORION feeder study [MDCO-PCS-17-03 (ORION-9), MDCO-PCS-17-04 (ORION-10), MDCO-PCS-17-08 (ORION-11) or MDCO-PCS-17-02 (ORION-5)] meaning the subject received the last dose of study drug and completed the final study visit per applicable protocol.

2. On current lipid-lowering therapies (such as a statin and/or ezetimibe) from previous study with no planned medication or dose change during study participation.

3. Willing and able to give informed consent before initiation of any study-related procedures and willing to comply with all required study procedures.

Exclusion Criteria:

1. Any uncontrolled or serious disease, or any medical or surgical condition, that may either interfere with participation in the clinical study, and/or put the subject at significant risk [according to investigator's (or delegate's) judgment] if he/she participates in the clinical study.

2. An underlying known disease, or surgical, physical, or medical condition that, in the opinion of the investigator (or delegate) might interfere with interpretation of the clinical study results.

3. Severe concomitant noncardiovascular disease that carries the risk of reducing life expectancy to less than 3 years,

4. Active liver disease defined as any known current infectious, neoplastic, or metabolic pathology of the liver or unexplained alanine aminotransferase (ALT), aspartate aminotransferase (AST), elevation >3x the upper limit of normal (ULN), or total bilirubin (TBIL) elevation >2x ULN at the last recorded visit in the feeder study prior to study entry visit.

5. Females who are pregnant or nursing, or who are of childbearing potential and unwilling to use at least one method of acceptable effective contraception (eg, oral contraceptives, barrier methods, approved contraceptive implant, long-term injectable contraception, 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. Planned use of other investigational medicinal products other than inclisiran or devices during the course of the study.

7. Any condition that according to the investigator could interfere with the conduct of the study, such as but not limited to:

1. Subjects who are unable to communicate or to cooperate with the investigator

2. Unable to understand the protocol requirements, instructions and study-related restrictions, the nature, scope, and possible consequences of the study (including subjects whose cooperation is doubtful due to drug abuse or alcohol dependency)

3. Unlikely to comply with the protocol requirements, instructions, and study-related restrictions (eg, uncooperative attitude, inability to return for follow-up visits, and improbability of completing the study)

4. Have any medical or surgical condition, which in the opinion of the investigator would put the subject at increased risk from participating in the study

5. Persons directly involved in the conduct of the study.

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

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

Overall Official
Last Name Role Affiliation
Scott Wright, MD Principal Investigator Mayo Clinic
Location
Facility:
Research Site 10001-015 | Birmingham, Alabama, 35211, United States
Research Site 10001-138 | Foley, Alabama, 36535, United States
Research Site 10001-113 | Huntsville, Alabama, 35801, United States
Research Site 10001-058 | Mobile, Alabama, 36608, United States
Research Site 10001-037 | Montgomery, Alabama, 36117, United States
Research Site 10001-076 | Saraland, Alabama, 36571, United States
Research Site 10001-013 | Chandler, Arizona, 85224, United States
Research Site 10001-077 | Mesa, Arizona, 85213, United States
Research Site 10001-136 | Phoenix, Arizona, 85014, United States
Research Site 10001-051 | Surprise, Arizona, 85374, United States
Research Site 10001-019 | Tucson, Arizona, 85712, United States
Research Site 10001-004 | Tucson, Arizona, 85741, United States
Research Site 10001-132 | Tucson, Arizona, 85745, United States
Research Site 10001-073 | Beverly Hills, California, 90211, United States
Research Site 10001-050 | Canoga Park, California, 91303, United States
Research Site 10001-011 | Carlsbad, California, 92008, United States
Research Site 10001-065 | El Cajon, California, 92020, United States
Research Site 10001-150 | Los Angeles, California, 90022, United States
Research Site 90001-005 | Mission Viejo, California, 92691, United States
Research Site 10001-043 | Northridge, California, 91324, United States
Research Site 10001-022 | Northridge, California, 91325, United States
Research Site 10001-033 | Sacramento, California, 95821-2134, United States
Research Site 10001-105 | San Ramon, California, 94582, United States
Research Site 10001-008 | Santa Rosa, California, 95405, United States
Research Site 10001-153 | Spring Valley, California, 91978, United States
Research Site 90001-015 | Stanford, California, 94305, United States
Research Site 10001-044 | Torrance, California, 90502, United States
Research Site 90001-047 | Boca Raton, Florida, 33434, United States
Research Site 10001-084 | Clearwater, Florida, 33756, United States
Research Site 10001-155 | Clearwater, Florida, 33756, United States
Research Site 10001-099 | Clearwater, Florida, 33761, United States
Research Site 10001-127 | Daytona Beach, Florida, 32117, United States
Research Site 10001-119 | Fleming Island, Florida, 32003, United States
Research Site 10001-070 | Fort Lauderdale, Florida, 33308, United States
Research Site 10001-067 | Hialeah, Florida, 33012, United States
Research Site 10001-139 | Jacksonville, Florida, 32204, United States
Research Site 10001-039 | Jacksonville, Florida, 32216, United States
Research Site 10001-098 | Jacksonville, Florida, 32216, United States
Research Site 10001-080 | Miami Springs, Florida, 33166, United States
Research Site 10001-081 | Miami, Florida, 33126, United States
Research Site 10001-140 | Miami, Florida, 33126, United States
Research Site 10001-142 | Miami, Florida, 33126, United States
Research Site 10001-030 | Miami, Florida, 33165, United States
Research Site 10001-116 | Miami, Florida, 33183, United States
Research Site 10001-027 | Pembroke Pines, Florida, 33024, United States
Research Site 10001-115 | Pembroke Pines, Florida, 33027, United States
Research Site 10001-048 | Pembroke Pines, Florida, 33029, United States
Research Site 10001-147 | Pembroke Pines, Florida, 33029, United States
Research Site 10001-003 | Pinellas Park, Florida, 33781, United States
Research Site 10001-104 | Ponte Vedra, Florida, 32081, United States
Research Site 10001-090 | Saint Augustine, Florida, 32086, United States
Research Site 10001-102 | Saint Petersburg, Florida, 33713, United States
Research Site 10001-123 | Sarasota, Florida, 34239-3513, United States
Research Site 10001-143 | Tampa, Florida, 33614, United States
Research Site 10001-069 | Atlanta, Georgia, 30342, United States
Research Site 10001-137 | Dunwoody, Georgia, 30338, United States
Research Site 10001-092 | Macon, Georgia, 31210, United States
Research Site 10001-059 | Arlington Heights, Illinois, 60005, United States
Research Site 10001-158 | Chicago, Illinois, 60652, United States
Research Site 10001-036 | Evanston, Illinois, 60201, United States
Research Site 10001-082 | Indianapolis, Indiana, 46260, United States
Research Site 10001-040 | Valparaiso, Indiana, 46383, United States
Research Site 10001-074 | West Des Moines, Iowa, 50266, United States
Research Site 10001-028 | Hutchinson, Kansas, 67502, United States
Research Site 10001-125 | Lexington, Kentucky, 40503, United States
Research Site 10001-108 | Lexington, Kentucky, 40504, United States
Research Site 10001-107 | Owensboro, Kentucky, 42303, United States
Research Site 10001-144 | Crowley, Louisiana, 70526, United States
Research Site 10001-041 | Lake Charles, Louisiana, 70601, United States
Research Site 10001-101 | Monroe, Louisiana, 71201, United States
Research Site 90001-004 | Boston, Massachusetts, 02114, United States
Research Site 10001-024 | Flint, Michigan, 48504, United States
Research Site 10001-095 | Grandville, Michigan, 49418, United States
Research Site 10001-078 | Sterling Heights, Michigan, 48310, United States
Research Site 10001-034 | Troy, Michigan, 48098, United States
Research Site 10001-018 | Edina, Minnesota, 55435, United States
Research Site 90001-056 | Saint Paul, Minnesota, 55102, United States
Research Site 10001-156 | Saint Louis, Missouri, 63136, United States
Research Site 10001-007 | Saint Louis, Missouri, 63141, United States
Research Site 90001-012 | Butte, Montana, 59701, United States
Research Site 10001-053 | Omaha, Nebraska, 68134, United States
Research Site 10001-021 | Omaha, Nebraska, 68144, United States
Research Site 90001-112 | Las Vegas, Nevada, 89119, United States
Research Site 10001-124 | Las Vegas, Nevada, 89121, United States
Research Site 10001-060 | Bridgewater, New Jersey, 08807, United States
Research Site 90001-014 | Summit, New Jersey, 07901, United States
Research Site 10001-055 | Warren, New Jersey, 07059, United States
Research Site 10001-054 | Albany, New York, 12206, United States
Research Site 10001-122 | Binghamton, New York, 13901, United States
Research Site 10001-128 | Endwell, New York, 13760, United States
Research Site 10001-042 | New Windsor, New York, 12553, United States
Research Site 10001-129 | Poughkeepsie, New York, 12601, United States
Research Site 10001-110 | Williamsville, New York, 14221, United States
Research Site 10001-063 | Cary, North Carolina, 27518, United States
Research Site 10001-064 | Greensboro, North Carolina, 27401, United States
Research Site 10001-145 | Mooresville, North Carolina, 28117, United States
Research Site 10001-046 | Shelby, North Carolina, 28150, United States
Research Site 10001-016 | Akron, Ohio, 443311, United States
Research Site 10001-120 | Cincinnati, Ohio, 45219, United States
Research Site 90001-002 | Cincinnati, Ohio, 45227, United States
Research Site 10001-010 | Cincinnati, Ohio, 45236, United States
Research Site 10001-134 | Cincinnati, Ohio, 45246, United States
Research Site 10001-014 | Columbus, Ohio, 43212, United States
Research Site 10001-141 | Dayton, Ohio, 45419, United States
Research Site 10001-148 | Marion, Ohio, 43302, United States
Research Site 10001-109 | Wyomissing, Pennsylvania, 19610, United States
Research Site 10001-001 | Anderson, South Carolina, 29621, United States
Research Site 10001-006 | Greer, South Carolina, 29651, United States
Research Site 10001-075. | Greer, South Carolina, 29651, United States
Research Site 10001-111 | Myrtle Beach, South Carolina, 29588, United States
Research Site 10001-133 | Pelzer, South Carolina, 29669, United States
Research Site 10001-103 | Rapid City, South Dakota, 57701, United States
Research Site 10001-146 | Athens, Tennessee, 37303, United States
Research Site 10001-130 | Kingsport, Tennessee, 37660, United States
Research Site 10001-118 | Knoxville, Tennessee, 37909, United States
Research Site 10001-106 | Knoxville, Tennessee, 37917, United States
Research Site 10001-100 | Amarillo, Texas, 79106, United States
Research Site 10001-087 | Austin, Texas, 78726, United States
Research Site 10001-117 | Austin, Texas, 78756, United States
Research Site 10001-009 | Dallas, Texas, 75234, United States
Research Site 10001-068 | Edinburg, Texas, 78503, United States
Research Site 10001-031 | Houston, Texas, 77002, United States
Research Site 10001-088 | Houston, Texas, 77024, United States
Research Site 10001-091 | Houston, Texas, 77027, United States
Research Site 10001-061 | Houston, Texas, 77058, United States
Research Site 10001-032 | Houston, Texas, 77070, United States
Research Site 10001-057 | New Braunfels, Texas, 78130, United States
Research Site 10001-079 | Round Rock, Texas, 78681, United States
Research Site 10001-071 | San Antonio, Texas, 78229, United States
Research Site 10001-083 | Schertz, Texas, 78154, United States
Research Site 10001-149 | Shavano Park, Texas, 78231, United States
Research Site 10001-045 | Tomball, Texas, 77375, United States
Research Site 10001-005 | Layton, Utah, 84041, United States
Research Site 10001-002 | Salt Lake City, Utah, 84123, United States
Research Site 10001-052 | Salt Lake City, Utah, 94107, United States
Research Site 10001-093 | Falls Church, Virginia, 22042, United States
Research Site 10001-085 | Manassas, Virginia, 20110, United States
Research Site 10001-094 | Midlothian, Virginia, 23114, United States
Research Site 10001-023 | Richmond, Virginia, 23294, United States
Research Site 10001-029 | Suffolk, Virginia, 23435, United States
Research Site 10001-114 | Tacoma, Washington, 98405, United States
Research Site 90011-005 | Chicoutimi, Quebec, G7H 7K9, Canada
Research Site 90011-001 | Montréal, Quebec, H2W 1R7, Canada
Research Site 90011-002 | Québec, Quebec, GIV 4W2, Canada
Research Site 11420-002 | Chomutov, 430 02, Czechia
Research Site 90420-001 | Praha, 140 21, Czechia
Research Site 90420-006 | Praha, 180 81, Czechia
Research Site 11420-003 | Uherské Hradiště, 686 01, Czechia
Research Site 90045-001 | Aalborg, Nordjylland, 9000, Denmark
Research Site 90045-004 | Esbjerg, 6700, Denmark
Research Site 90045-003 | Herning, 7400, Denmark
Research Site 90045-006 | Hvidovre, 2650, Denmark
Research Site 90045-002 | Roskilde, 4000, Denmark
Research Site 90045-005 | Viborg, 8800, Denmark
Research Site 11049-006 | Berlin, 12627, Germany
Research Site 11049-002 | Bochum, 47787, Germany
Research Site 11049-003 | Frankfurt, 60313, Germany
Research Site 11049-001 | Heidelberg, 69120, Germany
Research Site 11049-007 | Heidelberg, 69120, Germany
Research Site 11036-001 | Budapest, Hungary
Research Site 11036-004 | Debrecen, Hungary
Research Site 11036-002 | Hatvan, Hungary
Research Site 11036-003 | Zalaegerszeg, Hungary
Research Site 90031-001 | Amersfoort, 3813 TZ, Netherlands
Research Site 90031-003 | Amsterdam, 1105 AZ, Netherlands
Research Site 90031-006 | Goes, 4462 RA, Netherlands
Research Site 90031-009 | Hoorn, 1624 NP, Netherlands
Research Site 90031-005 | Utrecht, Netherlands
Research SIte 11048-016 | Brzozowie, Poland
Research Site 11048-018 | Bydgoszcz, 85-079, Poland
Research Site 11048-011 | Bydgoszcz, Poland
Research Site 11048-004 | Gdańsk, Poland
Research Site 11048-005 | Gdynia, Poland
Research Site 11048-007 | Katowice, Poland
Research SIte 11048-012 | Katowice, Poland
Research Site 11048-003 | Kraków, Poland
Research SIte 11048-014 | Kraków, Poland
Research Site 11048-008 | Lublin, Poland
Research Site 11048-001 | Poznań, Poland
Research Site 11048-019 | Ruda Śląska, 41-709, Poland
Research SIte 11048-013 | Rzeszów, Poland
Research SIte 11048-015 | Tarnów, Poland
Research Site 11048-006 | Warsaw, Poland
Research Site 11048-009 | Warsaw, Poland
Research Site 11048-002 | Wrocław, Poland
Research Site 11048-010 | Wrocław, Poland
Research Site 90027-008 | Bellville, Cape Town, 7530, South Africa
Research Site 90027-007 | Lyttelton, Cape Town, 0157, South Africa
Research Site 90027-003 | Bloemfontein, Free State, 9301, South Africa
Research Site 90027-010 | Johannesburg, Gauteng, 2193, South Africa
Research Site 11027-005 | Kempton Park, Gauteng, 1619, South Africa
Research Site 90027-006 | Pretoria, Gauteng, 0184, South Africa
Research Site 90027-009 | Witbank, Gauteng, 1035, South Africa
Research Site 90027-001 | Cape Town, Western Cape, 7500, South Africa
Research Site 11027-007 | Kuilsrivier, Western Cape, 7580, South Africa
Research Site 11027-013 | Paarl, Western Cape, 7646, South Africa
Research Site 90027-004 | Somerset West, Western Cape, 7130, South Africa
Research Site 90027-005 | Somerset West, Western Cape, 7130, South Africa
Research Site 90034-004 | Córdoba, Andalucia, 14004, Spain
Research Site 90034-002 | Zaragoza, Aragon, 5009, Spain
Research Site 90034-005 | Barcelona, Cataluna, 08036, Spain
Research Site 90034-006 | Barcelona, Cataluna, 08907, Spain
Research Site 90034-001 | Reus, Cataluna, 43204, Spain
Research Site 90034-003 | La Coruña, Galicia, 15002, Spain
Research Site 90046-002 | Göteborg, SE-41346, Sweden
Research Site 90046-001 | Stockholm, SE-11446, Sweden
Research Site 90046-003 | Stockholm, SE-14186, Sweden
Research Site 11380-005 | Cherkasy, Ukraine
Research Site 11380-008 | Kharkiv, 61176, Ukraine
Research Site 11380-001 | Kyiv, 02002, Ukraine
Research Site 11380-002 | Kyiv, 03037, Ukraine
Research Site 11380-003 | Kyiv, 03049, Ukraine
Research Site 11380-004 | Kyiv, Ukraine
Research Site 11380-009 | Zaporizhzhya, Ukraine
Research Site 11380-006 | Úzhgorod, 88000, Ukraine
Research Site 11044-028 | Bollington, Cheshire, SK10 5JH, United Kingdom
Research Site 11044-026 | Bury, United Kingdom
Research Site 11044-024 | Cheadle Hulme, United Kingdom
Research Site 11044-014 | Chorley, United Kingdom
Research Site 11044-012 | Cornwell, United Kingdom
Research Site 11044-010 | Derby, United Kingdom
Research Site 11044-006 | Edgbaston, United Kingdom
Research Site 11044-009 | Exeter, United Kingdom
Research Site 11044-001 | Glasgow, United Kingdom
Research Site 11044-008 | Hexham, United Kingdom
Research SIte 11044-020 | Macclesfield, United Kingdom
Research Site 11044-005 | Manchester, United Kingdom
Research Site 11044-025 | Manchester, United Kingdom
Research Site 11044-027 | Manchester, United Kingdom
Research Site 11044-029 | Manchester, United Kingdom
Research Site 11044-019 | Plymouth, United Kingdom
Research Site 11044-003 | Reading, United Kingdom
Research Site 11044-022 | Sale, United Kingdom
Research Site 11044-023 | Sale, United Kingdom
Research Site 11044-002 | Stockton-on-Tees, United Kingdom
Research Site 11044-021 | Timperley, United Kingdom
Research Site 11044-007 | Wales, United Kingdom
Research Site 11044-004 | Waterloo, United Kingdom
Location Countries

Canada

Czechia

Denmark

Germany

Hungary

Netherlands

Poland

South Africa

Spain

Sweden

Ukraine

United Kingdom

United States

Verification Date

September 2020

Responsible Party

Type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 1
Arm Group

Label: Inclisiran

Type: Experimental

Description: Inclisiran sodium 300 milligrams (mg) will be administered as a single SC injection on Day 1*, 90, then every 180 days to Day 990. *Subjects who received blinded placebo in the feeder study will receive blinded inclisiran and subjects who received blinded inclisiran in the feeder study will receive blinded placebo on Day 1 in ORION-8. Subjects from the open label ORION-5 study will not receive any injection of study drug/placebo on Day 1.

Acronym ORION-8
Patient Data No
Study Design Info

Allocation: N/A

Intervention Model: Single Group Assignment

Primary Purpose: Treatment

Masking: None (Open Label)

Source: ClinicalTrials.gov